menotropins and Polycystic-Ovary-Syndrome

Ovulation induction with follicle stimulating hormone (FSH) is a second-line treatment in women with polycystic ovary syndrome (PCOS) who do not ovulate or conceive on clomiphene citrate.. To compare the effectiveness and safety of gonadotrophins as a second-line treatment for ovulation induction in women with clomiphene citrate-resistant polycystic ovary syndrome (PCOS), and women who do not ovulate or conceive after clomiphene citrate.. In January 2018, we searched the Cochrane Gynaecology and Fertility Group Specialised Register of Controlled Trials, CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL, the World Health Organisation clinical trials register, Clinicaltrials.gov, LILACs, and PubMed databases, and Google Scholar. We checked references of in all obtained studies. We had no language restrictions.. All randomised controlled trials reporting data on clinical outcomes in women with PCOS who did not ovulate or conceive on clomiphene citrate, and undergoing ovulation induction with urinary-derived gonadotrophins, including urofollitropin (uFSH) in purified FSH (FSH-P) or highly purified FSH (FSH-HP) form, human menopausal gonadotropin (HMG) and highly purified human menopausal gonadotrophin (HP-HMG), or recombinant FSH (rFSH), or continuing clomiphene citrate. We included trials reporting on ovulation induction followed by intercourse or intrauterine insemination. We excluded studies that described co-treatment with clomiphene citrate, metformin, luteinizing hormone, or letrozole.. Three review authors (NW, EK, and MvW) independently selected studies for inclusion, assessed risk of bias, and extracted study data. Primary outcomes were live birth rate per woman and multiple pregnancy per woman. Secondary outcomes were clinical pregnancy, miscarriage, incidence of ovarian hyperstimulation syndrome (OHSS) per woman, total gonadotrophin dose, and total duration of stimulation per woman. We combined data using a fixed-effect model to calculate the risk ratio (RR). We summarised the overall quality of evidence for the main outcomes using GRADE criteria.. The review included 15 trials with 2387 women. Ten trials compared rFSH with urinary-derived gonadotrophins (three compared rFSH with human menopausal gonadotrophin, and seven compared rFSH with FSH-HP), four trials compared FSH-P with HMG. We found no trials that compared FSH-HP with FSH-P. One trial compared FSH with continued clomiphene citrate.Recombinant FSH (rFSH) versus urinary-derived gonadotrophinsThere may be little or no difference in the birth rate between rFSH and urinary-derived gonadotrophins (RR 1.21, 95% confidence interval (CI) 0.83 to 1.78; five trials, N = 505; I² = 9%; low-quality evidence). This suggests that for the observed average live birth per woman who used urinary-derived FSH of 16%, the chance of live birth with rFSH is between 13% and 28%. There may also be little or no difference between groups in incidence of multiple pregnancy (RR 0.86, 95% CI 0.46 to 1.61; eight trials, N = 1368; I² = 0%; low-quality evidence), clinical pregnancy rate (RR 1.05, 95% CI 0.88 to 1.27; eight trials, N = 1330; I² = 0; low-quality evidence), or miscarriage rate (RR 1.20, 95% CI 0.71 to 2.04; seven trials, N = 970; I² = 0; low-quality evidence). We are uncertain whether rFSH reduces the incidence of OHSS (RR 1.48, 95% CI 0.82 to 2.65, ten trials, n=1565, I² = 0%, very low-quality evidence).Human menopausal gonadotrophin (HMG) or HP-HMG versus uFSHWhen compared to uFSH, we are uncertain whether HMG or HP-HMG improves live birth rate (RR 1.28, 95% CI 0.65 to 2.52; three trials, N = 138; I² = 0%; very low quality evidence), or reduces multiple pregnancy rate (RR 2.13, 95% CI 0.51 to 8.91; four trials, N = 161; I² = 0%; very low quality evidence). We are also uncertain whether HMG or HP-HMG improves clinical pregnancy rate (RR 1.31, 95% CI 0.66 to 2.59; three trials, N = 102; I² = 0; very low quality evidence), reduces miscarriage rate (RR 0.33, 95% CI 0.06 to 1.97; two trials, N = 98; I² = 0%; very low quality evidence), or reduces the incidence of OHSS (RR 7.07, 95% CI 0.42 to 117.81; two trials, N = 53; very low quality evidence) when compared to uFSH.Gonadotrophins versus continued clomiphene citrateGonadotrophins resulted in more live births than continued clomiphene citrate (RR 1.24, 95% CI 1.05 to 1.46; one trial, N = 661; I² = 0%; moderate-quality evidence). This suggests that for a woman with a live birth rate of 41% with continued clomiphene citrate, the live birth rate with FSH was between 43% and 60%. There is probably little or no diff. There may be little or no difference in live birth, incidence of multiple pregnancy, clinical pregnancy rate, or miscarriage rate between urinary-derived gonadotrophins and recombinant follicle stimulating hormone in women with polycystic ovary syndrome. For human menopausal gonadotropin or highly purified human menopausal gonadotrophin versus urinary follicle stimulating hormone we are uncertain whether one or the other improves or lowers live birth, incidence of multiple pregnancy, clinical pregnancy rate, or miscarriage rate. We are uncertain whether any of the interventions reduce the incidence of ovarian hyperstimulation syndrome. We suggest weighing costs and convenience in the decision to use one or the other gonadotrophin. In women with clomiphene citrate failure, gonadotrophins resulted in more live births than continued clomiphene citrate without increasing multiple pregnancies.

Topics: Abortion, Spontaneous; Birth Rate; Clomiphene; Drug Resistance; Female; Fertility Agents, Female; Follicle Stimulating Hormone; Gonadotropins; Humans; Live Birth; Menotropins; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy; Pregnancy, Multiple; Randomized Controlled Trials as Topic

Several clinical studies have recently been published documenting the possible role of adjuvant growth hormone treatment in in vitro fertilization. These studies have been performed on different groups of patients including poor ovarian responders, patients with polycystic ovary syndrome and with hypogonadotrophic-hypogonadism. The aim of this review is to examine relevant studies in the last 25 years, on the use of growth hormone in assisted conception and trace the train of events that has lead to the resurgence of interest in this subject.

Topics: Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Human Growth Hormone; Humans; Hypogonadism; Menotropins; Oocytes; Ovulation Induction; Polycystic Ovary Syndrome; Reproductive Techniques, Assisted

Topics: Androgens; Chorionic Gonadotropin; Clomiphene; Diagnosis, Differential; Drug Therapy, Combination; Female; Fertility Agents, Female; Humans; Insulin Resistance; Menotropins; Polycystic Ovary Syndrome; Prognosis

Metformin has been used as a treatment in many studies of the infertility associated with polycystic ovary syndrome (PCOS). We will review the literature on this topic as it specifically relates to changes in body mass index (BMI), improvement in menstrual cyclicity, and effects on ovulation and pregnancy rates.. Review of studies addressing biochemical and clinical changes in women with PCOS on metformin.. Changes in BMI, menstrual cyclicity, ovulation rate, and pregnancy rate.. Metformin has been shown to produce small but significant reductions in BMI. Multiple observational studies have confirmed an improvement in menstrual cyclicity with metformin therapy. The studies addressing the concomitant use of metformin with clomiphene citrate initially predicted great success, but these have been followed by more modest results. There is little data in the literature concerning the use of metformin and hMGs.. Some (but not all) women with PCOS have improvements in their menstrual cycles while on metformin. The data supporting the use of metformin in ovulation induction with clomiphene citrate and hMG remain to be confirmed by large, randomized, prospective studies.

Topics: Body Mass Index; Clomiphene; Diet; Female; Humans; Hypoglycemic Agents; Menotropins; Menstrual Cycle; Metformin; Obesity; Ovulation Induction; Polycystic Ovary Syndrome

Complete maturation of oocytes is essential for the developmental competence of embryos. Any interventions in the growth phase of the oocyte and the follicle in the ovary will affect oocyte maturation, fertilization and subsequent embryo development. Oocyte size is associated with maturation and embryo development in most species examined and this may indicate that a certain size is necessary to initiate the molecular cascade of normal nuclear and cytoplasmic maturation. The minimum size of follicle required for developmental competence in humans is 5-7 mm in diameter. Maturation in vitro can be accomplished in humans, but is associated with a loss of developmental competence unless the oocyte is near completion of its preovulatory growth phase. This loss of developmental competence is associated with the absence of specific proteins in oocytes cultured to metaphase II in vitro. The composition of culture medium used successfully for maturation of human oocytes is surprisingly similar to that originally developed for maturation of oocytes in follicle culture in vitro. The presence of follicle support cells in culture is necessary for the gonadotrophin-mediated response required to mature oocytes in vitro. Gonadotrophin concentration and the sequence of FSH and FSH-LH exposure may be important for human oocytes, particularly those not exposed to the gonadotrophin surge in vivo. More research is needed to describe the molecular and cellular events, the presence of checkpoints and the role of gene expression, translation and protein uptake on completing oocyte maturation in vitro and in vivo. In the meantime, there are very clear applications for maturing oocytes in human reproductive medicine and the success rates achieved in some of these special applications are clinically valuable.

Topics: Animals; Cell Cycle; Cells, Cultured; Culture Media; Female; Fertilization in Vitro; Follicle Stimulating Hormone; Humans; Menotropins; Oocytes; Ovarian Follicle; Polycystic Ovary Syndrome; Superovulation; Tissue and Organ Harvesting

Elevation of endogenous LH levels may result in premature luteinization. This may also be associated with the increased rate of spontaneous abortion. Gonadotropin releasing hormone analogue (GnRHa) used prior to human menopausal gonadotropin (hMG/FSH) administration may improve the outcome of ovulation induction.. To assess if GnRHa pre-treatment plus FSH/hMG increase the rate of clinical pregnancy and/or decrease the rate of spontaneous abortion in women with WHO group 2 ovulatory dysfunction, compared with hMG/FSH alone.. The Cochrane Subfertility Review Group specialised register of controlled trials was searched.. All relevant published and unpublished RCTs were selected. Three RCTs were identified comparing these two approaches.. A diverse search strategy was employed, including hand-search of 43 core journals from 1966 to the present, bibliographies of relevant trials, MEDLINE database, abstracts from North American and European meetings and contact with authors of relevant papers. Relevant data were extracted independently by two reviewers using the standardised data extraction sheet. Validity was assessed in terms of method of randomisation, completeness of follow-up, presence or absence of crossover and co-intervention.. 2x2 tables were generated for all relevant outcomes. Odds ratios were generated using the Peto modified Mantel-Haenszel technique. Statistical heterogeneity was assessed using x2.. Studies were clinically and statistically homogenous. Common odds ratios for pregnancy per treatment cycle and moderate to severe ovarian hyperstimulation syndrome (OHSS) were 1.50 (0.72-3.12) and 1.40 (0.5-3.92) respectively.. These studies are too small to clearly demonstrate clinically significant differences in pregnancy rate between the two approaches. However, data from IVF studies suggest that there may be an increased risk of OHSS associated with GnRHa use. In the absence of evidence suggesting a benefit of GnRHa augmentation for PCOS, it should not be recommended as a standard treatment for this patient group. Further studies assessing live birth and OHSS rates are warranted.

Topics: Clomiphene; Drug Resistance; Drug Therapy, Combination; Female; Fertility Agents, Female; Gonadotropin-Releasing Hormone; Gonadotropins; Humans; Menotropins; Polycystic Ovary Syndrome

The risks of multiple pregnancy and ovarian hyperstimulation syndrome (OHSS) are increased in women with clomiphene resistance WHO group 2 dysfunction undergoing ovulation induction as well as the risk of spontaneous abortion if conception takes place. Semi-purified preparations of FSH have been developed in an effort to reduce the impact of exogenous LH, relatively high levels of which are present in human menopausal gonadotropin (hMG). Ovulation induction in women with clomiphene resistant WHO group 2 dysfunction who often have clinical features of polycystic ovarian syndrome (PCOS), is a major challenge. The risks of multiple pregnancy and ovarian hyperstimulation syndrome (OHSS) are increased in this population. There also appears to be an increased risk of spontaneous abortion in those who conceive, perhaps associated with elevated LH levels. Semi-purified preparations of FSH have been developed in an effort to reduce the impact of exogenous LH, relatively high levels of which are present in human menopausal gonadotrophins.. To determine the effectiveness of daily FSH versus daily hMG in women with clomiphene-resistant polycystic ovary syndrome (PCOS), in terms of rates of pregnancy and moderate to severe ovarian hyperstimulation syndrome (OHSS).. The Cochrane Subfertility Review Group specialised register of controlled trials was searched.. All RCTs relevant to the clinical question were selected.. A diverse search strategy was employed, including hand-search of 43 core journals from 1966 to the present, bibliographies of relevant trials, MEDLINE database, abstracts from North American and European meetings and contact with authors of relevant papers. Relevant data were extracted independently by two reviewers using the standardized data extraction sheet. Validity was assessed in terms of method of randomisation, completeness of follow-up, presence or absence of crossover and co-intervention.. 2x2 tables were generated for all relevant outcomes. Odds ratios were generated using the Peto modified Mantel-Haenszel technique. Statistical heterogeneity was assessed using x2.. No significant benefit was demonstrated from semi-purified FSH versus hMG in terms of pregnancy rate: common odds ratio per patient 0.66 (95% CI 0.35-1.24) and per cycle 0.89 (95% CI 0.51-1.53). FSH appeared to be associated with a reduction in moderate to severe OHSS: common odds ratios 0.2 (95% CI 0.09-0.46).. In women with PCOS, no significant difference could be demonstrated between FSH and hMG, in terms of pregnancy rate. However, given similar cost, potential advantages in terms of purity and a possible reduction in OHSS risk, highly purified or recombinant FSH are likely to be widely adopted in the future. Further research should consider live birth as a primary clinical outcome, given concerns over the association between high androgen and LH levels with spontaneous abortion risk.

Topics: Clomiphene; Estrogen Antagonists; Female; Fertility Agents, Female; Follicle Stimulating Hormone; Humans; Infertility, Female; Menotropins; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy

Topics: Female; Fertilization in Vitro; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Luteinizing Hormone; Menotropins; Oocytes; Ovarian Follicle; Polycystic Ovary Syndrome; Pregnancy; Pregnancy Outcome

Topics: Animals; Aromatase; Clomiphene; Drug Therapy, Combination; Estradiol; Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Gonadotropins; Granulosa Cells; Growth Hormone; Humans; Insulin-Like Growth Factor I; Menotropins; Ovarian Hyperstimulation Syndrome; Ovary; Ovulation; Polycystic Ovary Syndrome; Pregnancy; Rats

Topics: Abortion, Spontaneous; Albumins; Antineoplastic Agents, Hormonal; Buserelin; Estradiol; Female; Fertilization in Vitro; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Growth Hormone; Humans; Luteinizing Hormone; Menotropins; Oocytes; Ovarian Hyperstimulation Syndrome; Polycystic Ovary Syndrome; Pregnancy

Topics: Embryo, Mammalian; Female; Fertilization in Vitro; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Luteinizing Hormone; Menotropins; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Ovum; Polycystic Ovary Syndrome; Pregnancy; Pregnancy Rate

The risks of multiple pregnancy and ovarian hyperstimulation syndrome (OHSS) are increased in women with clomiphene resistance WHO group 2 dysfunction undergoing ovulation induction as well as the risk of spontaneous abortion if conception takes place. Semi-purified preparations of FSH have been developed in an effort to reduce the impact of exogenous LH, relatively high levels of which are present in human menopausal gonadotropin (hMG). Ovulation induction in women with clomiphene resistant WHO group 2 dysfunction who often have clinical features of polycystic ovarian syndrome (PCOS), is a major challenge. The risks of multiple pregnancy and ovarian hyperstimulation syndrome (OHSS) are increased in this population. There also appears to be an increased risk of spontaneous abortion in those who conceive, perhaps associated with elevated LH levels. Semi-purified preparations of FSH have been developed in an effort to reduce the impact of exogenous LH, relatively high levels of which are present in human menopausal gonadotrophins.. To determine the effectiveness of daily FSH versus daily hMG in women with clomiphene-resistant polycystic ovary syndrome (PCOS), in terms of rates of pregnancy and moderate to severe ovarian hyperstimulation syndrome (OHSS).. The Cochrane Subfertility Review Group specialised register of controlled trials was searched.. All RCTs relevant to the clinical question were selected.. A diverse search strategy was employed, including hand-search of 43 core journals from 1966 to the present, bibliographies of relevant trials, MEDLINE database, abstracts from North American and European meetings and contact with authors of relevant papers. Relevant data were extracted independently by two reviewers using the standardized data extraction sheet. Validity was assessed in terms of method of randomisation, completeness of follow-up, presence or absence of crossover and co-intervention.. 2x2 tables were generated for all relevant outcomes. Odds ratios were generated using the Peto modified Mantel-Haenszel technique. Statistical heterogeneity was assessed using x2.. No significant benefit was demonstrated from semi-purified FSH versus hMG in terms of pregnancy rate: common odds ratio per patient 0.66 (95% CI 0.35-1.24) and per cycle 0.89 (95% CI 0.51-1.53). FSH appeared to be associated with a reduction in moderate to severe OHSS: common odds ratios 0.2 (95% CI 0.09-0.46).. In women with PCOS, no significant difference could be demonstrated between FSH and hMG, in terms of pregnancy rate. However, given similar cost, potential advantages in terms of purity and a possible reduction in OHSS risk, highly purified or recombinant FSH are likely to be widely adopted in the future. Further research should consider live birth as a primary clinical outcome, given concerns over the association between high androgen and LH levels with spontaneous abortion risk.

Topics: Clomiphene; Estrogen Antagonists; Female; Fertility Agents, Female; Follicle Stimulating Hormone; Humans; Infertility, Female; Menotropins; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy

Elevation of endogenous LH levels may result in premature luteinization. This may also be associated with the increased rate of spontaneous abortion. Gonadotropin releasing hormone analogue (GnRHa) used prior to human menopausal gonadotropin (hMG/FSH) administration may improve the outcome of ovulation induction.. To assess if GnRHa pre-treatment plus FSH/hMG increase the rate of clinical pregnancy and/or decrease the rate of spontaneous abortion in women with WHO group two ovulatory dysfunction, compared with hMG/FSH alone.. The Cochrane Subfertility Review Group specialised register of controlled trials was searched.. All relevant published and unpublished RCTs were selected. Three RCTs were identified comparing these two approaches.. A diverse search strategy was employed, including hand-search of 43 core journals from 1966 to the present, bibliographies of relevant trials, MEDLINE database, abstracts from North American and European meetings and contact with authors of relevant papers. Relevant data were extracted independently by two reviewers using the standardised data extraction sheet. Validity was assessed in terms of method of randomisation, completeness of follow-up, presence or absence of crossover and co-intervention.. Two by two tables were generated for all relevant outcomes. Odds ratios were generated using the Peto modified Mantel-Haenszel technique. Statistical heterogeneity was assessed using by two.. Studies were clinically and statistically homogenous. Common odds ratios for pregnancy per treatment cycle and moderate to severe ovarian hyperstimulation syndrome (OHSS) were 1.50 (0.72-3.12) and 1.40 (0.5-3.92) respectively.. These studies are too small to clearly demonstrate clinically significant differences in pregnancy rate between the two approaches. However, data from IVF studies suggest that there may be an increased risk of OHSS associated with GnRHa use. In the absence of evidence suggesting a benefit of GnRHa augmentation for PCOS, it should not be recommended as a standard treatment for this patient group. Further studies assessing live birth and OHSS rates are warranted.

Topics: Clomiphene; Drug Resistance; Drug Therapy, Combination; Female; Fertility Agents, Female; Gonadotropin-Releasing Hormone; Gonadotropins; Humans; Menotropins; Polycystic Ovary Syndrome

To assess the efficacy of IVP-ET in infertile women with the polycystic ovary syndrome (PCOS) and to provide a comprehensive review of contemporary therapeutic options and their complications as reflected in the current literature.. Pertinent studies in medical literature identified through computerized bibliographic search and via manual review of relevant scientific publications.. In vitro fertilization and ET is an effective therapy for PCOS patients who are refractory to ovulation induction in vivo or who have coexisting infertility factors. The use of GnRH agonist (GnRH-a) is associated with significant reductions in the incidence of pregnancy loss and may improve fertilization and cleavage rates. In the PCOS patient, the use of purified FSH preparations does not appear to improve pregnancy rates nor other clinical parameters when compared with hMG. Severe ovarian hyperstimulation syndrome (OHSS) is an important consideration when PCOS patients undergo superovulation protocols. Strategies for OHSS prevention include the use of intravenous albumin immediately after oocyte retrieval, triggering of ovulation with a GnRH-a, or withholding menotropin therapy for several days before hCG administration. Cryopreservation of all embryos for future transfer in an artificial cycle has also proven to be an effective alternative in PCOS patients at high risk for severe OHSS.. Pregnancy rates for PCOS patients undergoing IVF-ET are comparable with those for women with tubal factor infertility. Therefore, IVF-ET should be offered to patients with PCOS who are refractory to conventional infertility modalities.

Topics: Embryo Transfer; Female; Fertilization in Vitro; Follicle Stimulating Hormone; Humans; Leuprolide; Menotropins; Ovarian Hyperstimulation Syndrome; Polycystic Ovary Syndrome; Pregnancy; Triptorelin Pamoate

Ovulation induction is one of the greatest success stories in reproductive endocrinology. With appropriate therapy in properly f1p4cted patients, the conception and live birth-rates in treated patients are almost indistinguishable from normal. In the estrogenized woman there are many different techniques to reverse the condition of chronic anovulation. With clomiphene citrate, up to 80% of patients will ovulate, and approximately half will conceive. In women who fail clomiphene therapy, injectable gonadotropins are usually successful in inducing ovulation. New protocols for administering these powerful agents have minimized the risk of ovarian hyperstimulation and multiple pregnancy. When medical therapy fails to result in successful ovulatory cycles, surgical treatments can be considered. Laparoscopic ovarian ablation has been shown to be effective treatment. Whether this less invasive surgery results in fewer adhesions than conventional ovarian wedge resection remains to be proven. By carefully considering each patient and individualizing treatment based on a full knowledge of alternatives, ovulation induction remains one of the most challenging and rewarding treatments in reproductive endocrinology.

Topics: Anovulation; Clomiphene; Estrogens; Female; Humans; Menotropins; Ovary; Ovulation Induction; Polycystic Ovary Syndrome

Topics: Androgens; Chorionic Gonadotropin; Clomiphene; Female; Gonadotropin-Releasing Hormone; Humans; Insulin Resistance; Menotropins; Ovariectomy; Polycystic Ovary Syndrome

Polycystic ovary syndrome (PCOS) is a complex disorder with heterogeneous clinical and endocrine features. Chronic anovulation and infertility are common and affect about 75% of the patients. Ovulation induction in PCOS patients is a challenge for the physicians who treat these patients. Several different treatment modalities have been proposed to induce ovulation in PCOS, each of which deals with a different clinical or endocrine disorder which is present in these patients. This review presents traditional and new methods for ovulation induction in PCOS patients, the theoretical background, the pros and cons for each treatment and success rate.

Topics: Clomiphene; Female; Follicle Stimulating Hormone; Growth Hormone; Humans; Hyperinsulinism; Menotropins; Obesity; Ovulation Induction; Polycystic Ovary Syndrome

A case of ovarian hyperstimulation syndrome is presented occurring in a young woman with polycystic ovary-like disease after induction of ovulation with the combined treatment of a luteinizing hormone releasing hormone analog and human menopausal gonadotrophins. Prevention and management based on pathophysiological considerations are reviewed.

Topics: Adult; Buserelin; Female; Humans; Menotropins; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Polycystic Ovary Syndrome

Ovarian hyperstimulation syndrome (OHSS) is the most serious iatrogenic complication of ovarian stimulation. In severe cases, haemoconcentration, hypovolaemia, thromboembolism and death may result. It is reassuring that its incidence is not increased after ovarian stimulation for in-vitro fertilization despite very high serum oestradiol levels and large numbers of follicles and oocytes. This may be related to follicular aspiration, expert monitoring or low implantation rates. However, complete prevention has not been achieved despite the wide availability of ultrasound and oestradiol assays, thus presenting the clinician with a continuous challenge. Our aim is to analyse critically the most recent published series of OHSS in in-vitro fertilization and other assisted reproduction techniques using stimulation with gonadotrophin releasing hormone agonists (GnRHa) and human menopausal gonadotrophin (HMG). The main determining factor in the development of OHSS appears to be ovarian predisposition. Patients with polycystic ovarian disease are at a high risk of OHSS and therefore a small dose and slow start of HMG is recommended, tailoring the dosage according to the ovarian response. Accurate prediction by ultrasound and oestradiol assays and strict prevention by withholding human chorionic gonadotrophin (HCG) or cryopreservation of all the embryos have a major impact on the occurrence of OHSS. It is interesting that fixed-schedule IVF cycles, without detailed monitoring, are not associated with an increased incidence of OHSS. The use of GnRHa, despite expectations, is associated with a higher prevalence of OHSS. Luteal phase supplementation with progesterone rather than HCG should be used in cycles where oestradiol is greater than 2500 ng/l or where the number of oocytes exceeded 10.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Humans; Menotropins; Ovarian Hyperstimulation Syndrome; Polycystic Ovary Syndrome; Triptorelin Pamoate

The patient with PCOD remains a challenge to the reproductive endocrinologist. Although successful induction of ovulation can often be achieved using standard therapeutic regimens of CC or hMG, too often this group of anovulatory patients fails to respond as expected. Over the past 10 to 15 years, alternate approaches to ovulation induction have been investigated with encouraging results. Whereas no one method is productive in all patients, these varied regimens offer us a number of options in dealing with this difficult clinical problem.

Topics: Clomiphene; Dexamethasone; Female; Follicle Stimulating Hormone; Humans; Menotropins; Ovulation Induction; Pituitary Hormone-Releasing Hormones; Polycystic Ovary Syndrome

Topics: Drug Evaluation; Female; Gonadotropin-Releasing Hormone; Humans; Menotropins; Ovulation; Polycystic Ovary Syndrome

GnRH analogues suppress LH fluctuations and produce a condition of hypogonadotropic hypogonadism. This action combined with treatment with human menopausal gonadotropins (hMG) has been exploited in programmes of induction of follicular growth in infertile women for both in vivo and in vitro fertilisation. There is improved clinical control over the process of ovulation and the phenomenon of premature luteinization in women with polycystic ovary disease has been eliminated.

Topics: Drug Therapy, Combination; Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Humans; Infertility, Female; Insemination, Artificial; Menotropins; Oocytes; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy

Induction of ovulation is difficult to achieve in patients with PCOD when they are resistant to therapy with clomiphene citrate; moreover, treatment with human menopausal gonadotropins subjects the PCOD patient to the risk of multifollicular ovulation and hyperstimulation. This article summarizes the hormonal picture and the initial therapeutic approach to the patient with PCOD. The proper administration, usage, and monitoring of conventional ovulation-inducing agents for these patients are discussed. Some of the newer approved agents that can be used in special patients who have not responded to conventional ovulation induction are also described.

Topics: Androgens; Chorionic Gonadotropin; Clomiphene; Drug Therapy, Combination; Estrogens; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Luteinizing Hormone; Menotropins; Ovulation Induction; Polycystic Ovary Syndrome

The amenorrhea associated with bilateral polycystic ovaries, described by Stein and Leventhal, actually represents a syndrome involving various organs and systems. Clinically, this symptom complex commonly presents as menstrual disturbances, infertility, excessive body weight, and hirsutism. An understanding of the pathophysiology that underlies these symptoms provides a logical basis for evaluation and treatment of the syndrome. The diagnostic approach may involve biochemical determinations (baseline, stimulated, and suppressed) and radiologic testing. Therapy is directed at chronic anovulation, the hyperandrogenism responsible for hirsutism and acne, and the prophylaxis against endometrial and breast carcinomas. Ovulation can be induced with various agents, many of which have a risk of ovarian hyperstimulation in the PCOD patient. The use of GnRH agonists with HMG or FSH for ovulation induction will probably increase in the future. Although classic wedge resection has little place in modern management of PCOD, the recent laparoscopic ovarian cautery remains largely unstudied with respect to long-term postoperative plasma androgen levels and pelvic adhesions. It is too premature to evaluate this new surgical therapy. Hirsutism is effectively treated with estrogen-progestin combinations, medroxyprogesterone acetate, androgen receptor blockers (spironolactone, cimetidine, cyproterone acetate, and cyproheptadine), and glucocorticoids. To date, the available GnRH agonists have not been found selective enough to be used in the treatment of hirsutism, owing to possible long-term complications. Most medical approaches should include electrolysis for permanent hair removal. At present, gynecologic surgery seems to have little place in the management of hirsutism.

Topics: Clomiphene; Diagnosis, Differential; Female; Follicle Stimulating Hormone; Glucocorticoids; Gonadotropin-Releasing Hormone; Hirsutism; Humans; Menotropins; Menstruation Disturbances; Ovulation Induction; Polycystic Ovary Syndrome; Weight Loss

Topics: Arcuate Nucleus of Hypothalamus; Catecholamines; Estrogens; Feedback; Female; Humans; Hypothalamus; Luteinizing Hormone; Median Eminence; Menotropins; Models, Biological; Pituitary Gland, Anterior; Pituitary Hormone-Releasing Hormones; Polycystic Ovary Syndrome; Puberty

With the use of pelvic ultrasound imaging we have found that more than half of the women presenting to our clinic with ovulatory disturbances have polycystic ovaries. As a group hirsutism is common, the serum LH, the LH:FSH ratio and serum androgen levels are higher than in other groups of patients with anovulation, but many of the women we studied were non-hirsute and had normal levels of these hormones. The aetiology of PCOS remains obscure and there is probably more than one cause. Disturbance of hypothalamic/pituitary, ovarian or adrenal function could all result in the development of polycystic ovaries. Our own data, based on pelvic ultrasound and measurement of serum androgen levels, suggest that an ovarian abnormality, other than the obvious morphological one, may be identified in most women although this does not prove (except perhaps in those women with unilateral PCOS) that the ovary is the primary site of the disturbance. Management of ovulatory disturbances includes symptomatic treatment of dysfunctional uterine bleeding and induction of ovulation. Although the ovulation rate following clomiphene is quoted as about 75%, this is probably an overestimate; less than half the 'ovulators' become pregnant and in those who do there is a high risk of early pregnancy loss. Induction of ovulation in clomiphene non-responders remains a difficult problem. The results of ovarian wedge resection are variable and any beneficial effect is short-lived with the risk of long-term infertility due to pelvic adhesions. Laparoscopic electrocautery may be a useful alternative, but it is too early to assess this form of treatment. Of the medical methods of ovulation induction in clomiphene non-responders, two methods have emerged as being highly promising: the first is administration of HMG following suppression of the pituitary by an LH-RH analogue; so far only a very small number of patients have been treated. The second is low-dose FSH. Initial studies, including our own, have shown a high incidence of ovulation and a pregnancy rate of 50%.

Topics: Androgens; Anovulation; Bromocriptine; Chorionic Gonadotropin; Clomiphene; Diagnosis, Differential; Estrogens; Female; Follicle Stimulating Hormone; Glucocorticoids; Gonadotropin-Releasing Hormone; Gonadotropins, Pituitary; Hirsutism; Humans; Hyperprolactinemia; Infertility, Female; Menotropins; Menstruation Disturbances; Obesity; Ovary; Ovulation Induction; Polycystic Ovary Syndrome; Ultrasonography

The polycystic ovarian syndrome remains one of the enigmas of gynaecological endocrinology. A review of the literature is presented, with emphasis on practical aspects, as illustrated by the results of a study of 139 patients with this condition. In the majority of patients the diagnosis entails clinical judgement combined with minimal biochemical determinations. However, the differential diagnosis may depend on sophisticated investigations. Since the treatment of some of these patients is as yet unsatisfactory, early diagnosis with prevention of androgenic side-effects is desirable.

Topics: Diagnosis, Differential; Female; Humans; Luteinizing Hormone; Menotropins; Polycystic Ovary Syndrome; Testosterone

Despite the efforts of a large number of investigators, the role of GnRH in clinical gynecology is uncertain. At present, its greatest utility is in research directed toward the understanding of hypothalamic-pituitary interrelationships. However, a clear understanding of the hypothalamic control of gonadotropin secretion awaits the actual measurement of the secretion of GnRH by the hypothalamus. In addition, a better understanding of the ability of the pituitary to secrete gonadotropins in various disorders of menstruation and maturation will probably be achieved through the determination of the capacity of the pituitary to synthesize as well as release gonadotropins in response to GnRH. Such determinations will probably utilize repeated or continuous infusions of GnRH rather than the currently more popular single injection technique. Finally, GnRH may be useful in the induction of ovulation. A definition of its role in ovulation induction awaits the results of additional clinical studies. Understanding of the nature of hypothalamic control of the pituitary is as yet incomplete. The availability of hypothalamic releasing factors will make it possible to study in greater detail the mechanisms by which the fine regulation of the endocrine system is achieved.

Topics: Adenoma; Amenorrhea; Clomiphene; Cushing Syndrome; Diabetes Mellitus; Disorders of Sex Development; Female; Galactorrhea; Humans; Hypogonadism; Hypothalamo-Hypophyseal System; Menotropins; Menstruation; Myotonic Dystrophy; Ovulation; Pituitary Diseases; Pituitary Neoplasms; Polycystic Ovary Syndrome; Postpartum Period; Pregnancy

Is sequential letrozole/human menopausal gonadotrophin (HMG) superior to letrozole alone in ovulation induction and pregnancy promotion among infertile women with polycystic ovary syndrome (PCOS)?. This open-label randomized controlled trial comparing sequential letrozole/HMG and letrozole alone included 174 participants enrolled from August 2019 to January 2020 at the Union Hospital of Tongji Medical College, Huazhong University of Science and Technology. Infertile women aged between 18 and 40 years who met Rotterdam criteria for PCOS and without other known causes of infertility were selected for this study. Patients were randomly assigned at a 1:1 ratio to receive 2.5 mg letrozole on cycle days 3-7 (n = 87) or 2.5 mg letrozole on cycle days 3-7 with a sequential injection of 75 IU HMG on cycle days 8-10 for one treatment cycle (n = 87). The pregnancy outcome was recorded after one treatment cycle.. Women receiving sequential treatment achieved a significantly higher ovulation rate than those in the letrozole group (90.8% versus 70.1%, P = 0.001) and the live birth rate of the sequential group was significantly higher than that of the letrozole protocol (23.0% versus 10.3%, P = 0.025); there was no statistical variation with respect to adverse events.. The data suggest that the sequential letrozole/HMG protocol may be superior to the letrozole alone protocol in terms of ovulation induction and pregnancy promotion among infertile women with PCOS.

Topics: Adolescent; Adult; Clomiphene; Female; Fertility Agents, Female; Gonadotropins; Humans; Infertility, Female; Letrozole; Menotropins; Ovulation; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy; Pregnancy Rate; Young Adult

The purpose of this research was to evaluate the efficacy of 3 ovulation induction therapies for treating infertility in patients with polycystic ovary syndrome (PCOS). In this retrospective study, we compared the success rates of 90 patients who underwent intrauterine insemination, who were randomly assigned to 1 of 3 treatment groups: letrozole (LE) + urinary gonadotropin (human menopausal gonadotropin [HMG]), clomiphene (CC) + HMG, or HMG alone. Using ultrasound scanning, we examined the number of mature follicles, ovulation rate, clinical pregnancy rate, endometrial thickness, and blood flow. When compared to the other 2 groups, the LE + HMG group had significantly higher levels of mature follicles, ovulation rate, clinical pregnancy rate, estradiol, and luteinizing hormone on the day of the human chorionic gonadotropin injection and endometrial receptivity (P < .05). There was no statistically significant difference between the 3 groups in terms of abortion rate, ectopic pregnancy rate, or adverse reactions. In this research, we found that infertility in patients with PCOS could be effectively treated by combining LE with HMG. This protocol increased ovulation, boosted fertility, and enhanced endometrial receptivity with no increase in adverse reactions. Therefore, it may be a useful clinical approach for inducing ovulation and treating infertility in patients with PCOS.

Topics: Female; Fertility Agents, Female; Humans; Infertility, Female; Letrozole; Menotropins; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy; Retrospective Studies

To compare the effects of letrozole and human menopausal gonadotropin (HMG) in the treatment of patients with polycystic ovary syndrome (PCOS) resistant to clomiphene citrate (CC).. A total of 96 clomiphene resistance polycystic ovary syndrome patients infertility were randomly divided into an LE group, and HMG group (n = 48). LE group orally received letrozole at 5.0 mg/d on the 3rd-5th days of menstrual cycle for 5 consecutive days, and 75 U/d HMG was given through intramuscular injection for 5 days starting from the third day of menstrual cycle in HMG group. Number of growing and mature follicles, serum E2 (pg/mL), serum P (ng/mL), endometrial thickness, occurrence of pregnancy and miscarriage were observed.. There was no significant difference in the number of ovulation cycles between the 2 groups (53.6% vs 64.7%, P > .05). The number of mature follicular cycles in the HMG group was higher than that of the letrozole group (P < .01). There were no significant differences in the clinical pregnancy rate (22.9% vs 27.1%, P > .05) and abortion rate (6.2% vs 10.4%, P > .05). There was no significant difference in the endometrial thickness between the 2 groups on the day of HCG injection [(9.1 ± 0.2) mm vs (10.7 ± 1.6) mm, P > .05]; the serum estradiol (E2) was lower in the letrozole group. The incidence of ovarian cysts was lower than that of HMG group (P < .05). There was2 ovarian hyperstimulation syndrome in the letrozole group; the incidence of ovarian hyperstimulation syndrome in the HMG group was 12.5%.. Letrozole-induced ovulation can obtain ovulation rate and pregnancy rate similar to gonadotropin, but reduce the risk associated with treatment. It can be used as an effective ovulation option for patients with polycystic ovary syndrome who are resistant to clomiphene.

Topics: Abortion, Spontaneous; Adult; Clomiphene; Endometrium; Estradiol; Female; Humans; Infertility, Female; Letrozole; Menotropins; Ovarian Cysts; Ovarian Hyperstimulation Syndrome; Ovulation; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy; Young Adult

Considering that clinical trial studies are limited in polycystic ovary syndrome (PCOS) patients, and there is no consensus on an optimum endometrial preparation protocol for frozen embryo transfer (FET), the present study was designed as a randomized clinical trial to compare the reproductive outcomes following stimulated cycles with letrozole plus human menopausal gonadotropin (HMG) for endometrial preparation compared with routine AC-FET.. This randomized controlled trial was carried out on infertile PCOS patients who underwent IVF/ICSI and FET cycles in Arash Women's Hospital affiliated to Tehran University of Medical Sciences between September 2018 and January 2020. PCOS diagnosis was based on the Rotterdam criteria. Eligible patients were randomly allocated into two groups: stimulated cycle with letrozole plus (HMG) (intervention group) and routine artificial hormonal endometrial preparation (control group).. One hundred seventy-seven infertile patients were recruited for participation in the study. Of these, 57 women were excluded due to non-eligibility for entering the study, and a total of 120 patients were randomly assigned to two study groups. After follow up, the cycle outcomes of 57 patients in the intervention group and 59 patients in the control group were compared. The data analysis showed that the two groups did not have significant differences in fundamental and demographic characteristics. After the intervention, there were no significant differences in implantation rate, chemical, ectopic, and clinical pregnancy rates between groups. Moreover, the rates of miscarriage and ongoing pregnancy were similar between groups (P > 0.05).. We found similar pregnancy outcomes with two endometrial preparation methods. Noting that each treatment centre should select the most beneficial and cost-effective method with the least adverse effects for patients, letrozole preparations for FET could be incorporated into possible options; however, establishing this approach as first-line treatment is premature in light of current evidence, and future randomized clinical trials with larger sample sizes are required for widespread application.. The study was also registered in the Iranian Registry of Clinical Trials on March 20th, 2020. ( IRCT20090526001952N12 at www.irct.ir , registered retrospectively).

Topics: Adult; Cryopreservation; Embryo Implantation; Embryo Transfer; Endometrium; Female; Humans; Letrozole; Menotropins; Outcome Assessment, Health Care; Polycystic Ovary Syndrome; Pregnancy; Pregnancy Outcome; Pregnancy Rate

To investigate the optimal ovulation induction with the combination of combining letrozole(LE),clomiphene citrate (CC),and human menopausal gonadotropin (HMG) in polycystic ovary syndrome(PCOS) patients resistant to CC or LE.. Two hundreds nine PCOS patients (209 cycles) resistant to CC or LE were randomly divided into three groups: CC+HMG group (59 cycles),LE+HMG group (72 cycles) and LE+CC group (78 cycles).The patients in LE+CC group unable to form the dominant follicle after 54 cycles were enrolled into LE+CC+HMG group.Maximum follicle diameter (MFD),endometrial thickness,number of follicles (diameter>1.4 cm),the level of serum estradiol (E2) were measured on the day of HMG administration.Also these results were observed and compared including the duration of treatment,dosage of HMG,number of ovulated follicles,clinical pregnancy rate,biochemical pregnancy rate,early abortion rate,twinning rate,and ectopic pregnancy rate.. The ovulation rate was significantly lower in LE+CC group (30.77%) (. Combintion of LE with CC could achieve 1/3 ovulation induction in PCOS resistant to CC or LE alone.When both combined with HMG,the induction of ovulation could be significantly higher than LE+HMG and CC+HMG,while the risk of multiple pregnancy and OHSS was reduced.

Topics: Clomiphene; Drug Therapy, Combination; Female; Fertility Agents, Female; Humans; Infertility, Female; Letrozole; Menotropins; Nitriles; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy; Triazoles

Ovarian hyperstimulation syndrome (OHSS) during ovarian stimulation is a current challenge for patients with polycystic ovarian syndrome (PCOS). Our previous studies indicated that progestin can prevent premature luteinizing hormone (LH) surge or moderate/severe OHSS in the general subfertile population, both in the follicular-phase and luteal-phase ovarian stimulation but it is unclear if this is true for patients with PCOS. The aim of the article was to analyze cycle characteristics and endocrinological profiles using human menopausal gonadotropin (hMG) in combination with medroxyprogesterone acetate (MPA) for PCOS patients who are undergoing IVF/intracytoplasmic sperm injection (ICSI) treatments and investigate the subsequently pregnancy outcomes of frozen embryo transfer (FET). In the randomized prospective controlled study, 120 PCOS patients undergoing IVF/ICSI were recruited and randomly classified into 2 groups according to the ovarian stimulation protocols: hMG and MPA (group A, n = 60) or short protocol (group B, n = 60). In the study group, hMG (150-225IU) and MPA (10 mg/d) were administered simultaneously beginning on cycle day 3. Ovulation was cotriggered by a gonadotropinreleasing hormone (GnRH) agonist (0.1 mg) and hCG (1000IU) when dominant follicles matured. A short protocol was used as a control. The primary end-point was the ongoing pregnancy rate per transfer and incidence of OHSS. Doses of hMG administrated in group A are significantly higher than those in the controls. LH suppression persisted during ovarian stimulation and no incidence of premature LH surge was seen in both groups. The fertilization rate and the ongoing pregnant rate in the study group were higher than that in the control. The number of oocytes retrieved, mature oocytes, clinical pregnancy rates per transfer, implantation rates, and cumulative pregnancy rates per patient were comparable between the 2 groups. The incidence of OHSS was low between the 2 groups, with no significant difference. The study showed that MPA has the advantages of an oral administration route, easy access, more control over LH levels. A possible reduction in the incidence of moderate or severe OHSS with the MPA protocol should be viewed with caution as the data is small. Large randomized trials with adequate sample size remain necessary.

Topics: Administration, Oral; Adult; Cross-Over Studies; Double-Blind Method; Embryo Transfer; Female; Fertilization; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Humans; Luteinizing Hormone; Medroxyprogesterone Acetate; Menotropins; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy; Pregnancy Outcome; Prospective Studies; Sperm Injections, Intracytoplasmic

To assess which is the optimal protocol in terms of endometrial preparation prior to frozen-thawed embryo transfer (FET) in women with polycystic ovarian syndrome (PCOS) and to explore the effect in stimulated cycle with the addition of vaginal 17-β oestradiol.. Five hundred and seventy-six patients with PCOS were prepared for FET using artificial cycle induced with oestradiol and progesterone supplementation (n = 291) and stimulated cycle induced by human menopausal gonadotrophin (HMG) within or without the addition of vaginal 17-β oestradiol (n = 285). Then the FET was performed in a receptive endometrium.. Endometrial thickness was similar (9.03 ± 1.65 vs. 9.12 ± 1.58, P > 0.05) in artificial and stimulated cycle. The two protocols resulted in clinical pregnancy rate (41.0 % vs. 41.6 %, P > 0.05), ongoing pregnancy rate (36.6 % vs. 34.7 %, P > 0.05), live birth rate (30.0 % vs. 31.7 %, P > 0.05), which were not statistically different. Nevertheless, the cancelled cycle rate made a significant difference (2.2 % vs. 5.4 %, P < 0.05). There is no significant difference in the clinical pregnancy rate in HMG, HMG added with vaginal oestradiol and HMG switch to vaginal oestradiol group (42.6 %, 41.1 %, and 33.3 %, respectively).. The mean endometrial thickness, clinical pregnancy rate, ongoing pregnancy rate, live birth rate and implantation rate were similar in artificial and stimulated cycle for endometrial preparation prior to FET in PCOS. It was fine to add vaginal 17-β oestradiol to stimulated cycle when necessary. However, stimulated cycles had a significantly higher cancelled cycle rate. We should follow the principles of individualization, securitization and optimization in endometrial preparation of the FET in patients with PCOS.

Topics: Adult; Birth Rate; Cryopreservation; Embryo Implantation; Embryo Transfer; Endometrium; Estradiol; Female; Humans; Menotropins; Polycystic Ovary Syndrome; Pregnancy; Pregnancy Rate; Progesterone; Prospective Studies

Gonadotropin has been used to stimulate ovulation in clomiphene-resistant infertile women with polycystic ovary syndrome (PCOS), but it is associated with overstimulated cycles with the development of many follicles. The aim of the study was to evaluate the effectiveness and efficacy of letrozole and clomiphene citrate (CC) combined with human menopausal gonadotropin (HMG) in CC-resistant infertile women with PCOS.. Ninety-four women received the letrozole + HMG, 90 women received CC + HMG, and 71 women received HMG only. All women received one treatment regimen in one treatment cycle. All patients were given HMG 75 IU on alternate days daily starting on day 3 or day 7 until the day of administration of human chorionic gonadotropin.. The rate of monofollicular development was 80.2% in the letrozole + HMG group, 65.3% in the CC + HMG group, and 54.7% in the HMG-only group (P<0.05 for letrozole + HMG vs the other two groups). The number of developing follicles (≥14 mm follicles) and the cycle cancellation rate due to ovarian hyperresponse were the lowest in the letrozole + HMG group, but the difference was not significant. The ovulation and pregnancy rate were similar among the three protocols. The HMG dose needed and the mean duration of treatment were significantly lower in the letrozole + HMG and CC + HMG groups compared with the HMG-only group.. Letrozole in combination with HMG is an effective protocol for reducing the risks of hyperstimulation for ovarian induction in CC-resistant women with PCOS. This combination may be more appropriate in patients who are particularly sensitive to gonadotropin.

Topics: Adult; Clomiphene; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Fertility Agents, Female; Humans; Infertility, Female; Letrozole; Menotropins; Nitriles; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy; Pregnancy Rate; Prospective Studies; Treatment Outcome; Triazoles; Young Adult

Administration of exogenous progesterone for luteal phase support has become a standard of practice. Intramuscular (IM) injections of progesterone in oil (PIO) and vaginal administration of progesterone are the primary routes of administration. This report describes the administration preferences expressed by women with infertility that were given progesterone vaginal insert (PVI) or progesterone in oil injections (PIO) for luteal phase support during fresh IVF cycles.. A questionnaire to assess the tolerability, convenience, and ease of administration of PVI and PIO given for luteal phase support was completed by infertile women diagnosed with PCOS and planning to undergo IVF. The women participated in an open-label study of highly purified human menopausal gonadotropins (HP-hMG) compared with recombinant FSH (rFSH) given for stimulation of ovulation.. Most women commented on the convenience and ease of administration of PVI, while a majority of women who administered IM PIO described experiencing pain. In addition, their partners often indicated that they had experienced at least some anxiety regarding the administration of PIO. The most distinguishing difference between PVI and PIO in this study was the overall patient preference for PVI. Despite the need to administer PVI either twice a day or three times a day, 82.6% of the patients in the PVI group found it "very" or "somewhat convenient" compared with 44.9% of women in the PIO group.. The results of this comprehensive, prospective patient survey, along with findings from other similar reports, suggest that PVI provides an easy-to-use and convenient method for providing the necessary luteal phase support for IVF cycles without the pain and inconvenience of daily IM PIO. Moreover, ongoing pregnancy rates with the well-tolerated PVI were as good as the pregnancy rates with PIO.. ClinicalTrial.gov, NCT00805935.

Topics: Administration, Intravaginal; Adult; Embryo Transfer; Female; Fertilization in Vitro; Follicle Stimulating Hormone; Humans; Infertility, Female; Injections, Intramuscular; Luteal Phase; Menotropins; Patient Preference; Polycystic Ovary Syndrome; Pregnancy; Pregnancy Rate; Progesterone; Prospective Studies; Recombinant Proteins; Surveys and Questionnaires; Treatment Outcome; Young Adult

Reduction of serum total testosterone (TT) is associated with pregnancy rate in polycystic ovary syndrome (PCOS) women receiving metformin, but most of the studies focus on the changes of basal levels of TT. The aim of this study was to evaluate whether the TT level around the ovulation period is related to the outcome of pregnancy in women with PCOS.. In total, 30 non-obese PCOS women with clomiphene citrate (CC) resistance from the Medical College's Reproductive Health Center were enrolled and randomly assigned to be treated with placebo (Group 1) or metformin (850 mg) (Group 2) twice daily for 3 months as the pre-treatment. Then, metformin alone was administered with CC, human menopausal gonadotropin (HMG) and human chorionic gonadotropin (HCG) to induce ovulation for 3 months in Group 1. In Group 2, CC/HMG/HCG was used to induce ovulation for 3 months without metformin. Follicle-stimulating hormone, luteinizing hormone, estradiol and TT levels before and after ovulation in pregnant cycles and non-pregnant cycles were evaluated over the course of treatment.. A total of 26 subjects completed 65 cycles. The TT levels after ovulation in the pregnant cycles were significantly lower than in the non-pregnant cycles in both groups (P = 0.001 and P < 0.001, respectively).. The level of TT after ovulation may be of prognostic value for pregnancy in non-obese women with PCOS and CC resistance during treatment.

Topics: Adult; Chorionic Gonadotropin; Clomiphene; Drug Resistance; Drug Therapy, Combination; Estradiol; Female; Fertility Agents, Female; Follicle Stimulating Hormone; Humans; Luteinizing Hormone; Menotropins; Metformin; Ovarian Follicle; Ovulation Induction; Pilot Projects; Polycystic Ovary Syndrome; Pregnancy; Pregnancy Rate; Prognosis; Reproductive Control Agents; Testosterone; Ultrasonography

To evaluate the efficacy of GnRH antagonist in comparison with the GnRH agonist protocol in OCP pretreated polycystic ovary syndrome (PCOs) patients undergoing their first ART cycle.. Prospective randomized controlled trial. University-based tertiary fertility center. Ninety-five PCOs patients under 35 years of age, with primary infertility were randomized to an ovarian stimulation protocol consisting of either. GnRh antagonist (study group) or GnRH agonist (control group) after pretreatment with OCP. Coasting or GnRH agonist Trigger was used when estradiol level > or =3,000 pgr/ml in the control and study group, respectively. Both groups received 800 mg vaginal progesterone and 4 mg oral estradiol valerate for luteal phase support.. There was no statistically significant difference in the age, body mass index, basal FSH, duration of infertility, the number of oocytes retrieved, the number of embryos transferred, Serum E2 levels on day of trigger, fertilization rate, chemical and clinical pregnancy rates between the two groups. None of the patients in the study group developed ovarian hyperstimulation syndrome (OHSS) compared with 22.2% of patients in the control group. Total duration of treatment and the number of HMG ampoules used were lower in the study group.. Antagonist protocol and GnRH agonist trigger for ovulation whenever necessary has a similar cycle outcome to the GnRH-agonist protocol in OCP pretreated PCOs patients, with significantly reduced risk of OHSS.

Topics: Adult; Buserelin; Contraceptives, Oral, Combined; Drug Administration Schedule; Drug Therapy, Combination; Ethinyl Estradiol-Norgestrel Combination; Female; Fertility Agents, Female; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Infertility, Female; Menotropins; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy; Pregnancy Rate; Young Adult

The objective of the present study was to investigate the response patterns of insulin-like growth factors (IGFs) and interleukin-6 (IL-6) to ovarian stimulation within 24 h in patients with polycystic ovary syndrome (PCOS) in comparison with normally ovulating women. This controlled prospective clinical study involved 60 women who attended an infertility clinic. For the induction of the ovarian stimulation, fifty-two patients with PCOS and eight control cases were injected with human menopause gonadotropin (hMG) and human chorionic gonadotropin (hCG) during the early follicular phase of the natural or induced menstrual cycle. The blood was sampled before (0h) and 6, 12, 18, and 24 h after the stimulation. Serum levels of estradiol (E2), IGF-I, IGF-II and IL-6 were measured by radioimmunoassay. A significant decrease in serum IGF-II at 12 h was observed after a mixture of hMG and hCG was administered in patients with polycystic ovaries (PCO) including the typical PCOS group and the PCO + OA group (accumulated p < 0.05), while normal women presented a slight decrease (accumulated p < 0.1) 18h after the stimulation. Moreover, all the groups had similar serum levels of IL-6 and IGF-I at all time points. An increase in serum E2 occurred coincident with a decrease in IGF-II in all the groups except the ovarian hyperandrogenism patients (HA + OA group). Serum IGF-II levels, which appeared to be negatively correlated with elevated E2, statistically decreased in PCO patients early after hMG and hCG administration when monitored for 24 h, while no such changes were observed in IGF-I and IL-6.

Topics: Adult; Chorionic Gonadotropin; Estradiol; Female; Humans; Insulin-Like Growth Factor I; Insulin-Like Growth Factor II; Interleukin-6; Menotropins; Ovulation Induction; Polycystic Ovary Syndrome

The purpose of this study was to test the effect of extended clomiphene citrate treatment compared with gonadotrophin therapy for the management of clomiphene-resistant women with polycystic ovary syndrome (PCOS). The study comprised 318 women (802 cycles) with clomiphene-resistant PCOS randomized to two treatment groups. Patients in the clomiphene citrate group were given 100 mg of clomiphene citrate daily starting on day 2 of menses for 9 days (160 patients, 405 cycles) while patients in the gonadotrophin group were given human menopausal gonadotrophin 75 IU intramuscularly daily for 5 days starting on day 3 of menses (158 patients, 397 cycles). The number of ovulating patients was significantly higher (P = 0.001) in the gonadotrophin group (57.6 versus 28.1%). The total number of follicles during stimulation was significantly greater (P = 0.01) in the gonadotrophin group (6.7 +/- 0.3 versus 4.1 +/- 0.4). Pregnancy occurred in 46/405 cycles in the clomiphene citrate group (11.4%) and in 80/397 cycles (20.2%) in the gonadotrophin group; the difference was statistically significant (P = 0.03). The extended clomiphene citrate regimen resulted in modest ovulation and pregnancy rates with no side effects. This therapy seems to offer economic, efficacy and safety advantages and it is worth undergoing before starting more expensive or sophisticated alternatives.

Topics: Adult; Clomiphene; Drug Resistance; Female; Fertility Agents, Female; Humans; Menotropins; Polycystic Ovary Syndrome; Pregnancy; Pregnancy Rate

Patients with polycystic ovary syndrome (PCOS) are highly sensitive to gonadotropins. In recent years a number of publications have shown that chronic low-dose protocols are effective in reducing complications, in particular ovarian hyperstimulation syndrome (OHSS), especially if recombinant human follicle stimulating hormone (rhFSH) is used. The aim of the present study was to compare the efficacy and safety of rhFSH (Gonal-F, Serono) versus urinary human FSH (uhFSH) (Metrodin, Serono) in a low-dose step-up protocol for ovulation induction in clomiphene-resistent infertile PCOS patients. Twenty PCOS patients were recruited in two centers for an open randomized comparative study. A starting dose of a 75-IU ampule of rhFSH or uhFSH was used for 14 days with an increment of 37.5 IU every 7 days. Human chorionic gonadotropin (hCG) (10,000 IU, Profasi, Serono) was administered if one to three follicles achieved a diameter of > or = 16 mm. Sonographic and hormonal (serum estradiol and progesterone) monitoring of the cycles was performed. All the six pregnancies induced were in the rhFSH group, but two of them ended with miscarriage. There were no differences between the two groups concerning the number of ampules used, the stimulation days, the estradiol levels on the day of hCG administration, and the progesterone levels 7 days after hCG administration. Three patients had grade II, and one patient grade III OHSS. In conclusion, our results support the literature data that rhFSH is superior to uhFSH regarding pregnancy rates, not only in in vitro fertilization cycles, but also with a low-dose protocol in patients with PCOS.

Topics: Drug Administration Schedule; Female; Fertility Agents, Female; Follicle Stimulating Hormone, Human; Humans; Hungary; Injections, Intramuscular; Injections, Subcutaneous; Menotropins; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy; Pregnancy Outcome; Recombinant Proteins; Treatment Outcome

Patients with polycystic ovary syndrome (PCOS) may need a longer period of pituitary downregulation to suppress the elevated serum LH and androgen levels effectively during IVF treatment using the GnRH agonist long protocol. We proposed a stimulation protocol incorporating Diane-35 and GnRH antagonist (Diane/cetrorelix protocol) and compared it with the GnRH agonist long protocol for PCOS patients.. Part I of the study was an observational pilot study to evaluate the hormonal change as a result of the Diane/cetrorelix protocol (n = 26). Part II of the study was a prospective randomized study comparing the Diane/cetrorelix protocol (n = 25) and the GnRH agonist long protocol (n = 24). In the Diane/cetrorelix protocol, patients were pre-treated with three cycles of Diane-35, followed by 0.25 mg of cetrorelix on cycle day 3. From day 4, cetrorelix and gonadotrophin were administered concomitantly until the day of HCG injection.. Serum LH, estradiol and testosterone levels were suppressed comparably in both protocols at the start of gonadotrophin administration. Serum LH was suppressed at constant levels without a premature LH surge in the Diane/cetrorelix protocol. The clinical results for both protocols were comparable, with significantly fewer days of injection, lower amounts of gonadotrophin used and lower estradiol levels on the day of HCG injection following the Diane/cetrorelix protocol. Furthermore, there was no significant difference in clinical pregnancy outcome between the two stimulation protocols.. The Diane/cetrorelix protocol has a similar pregnancy outcome to the GnRH agonist long protocol for women with PCOS undergoing IVF treatment.

Topics: Adult; Androgen Antagonists; Cyproterone Acetate; Drug Combinations; Drug Therapy, Combination; Ethinyl Estradiol; Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Hormone Antagonists; Hormones; Humans; Incidence; Infertility, Female; Menotropins; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pilot Projects; Polycystic Ovary Syndrome; Pregnancy; Pregnancy Outcome; Pregnancy Rate; Premedication

Recognition of the importance of insulin resistance in clomiphene-resistant women with polycystic ovary syndrome (PCOS) has led to the use of insulin sensitizers.. A randomized, controlled trial was conducted to compare efficacy of sequential treatment with metformin and clomiphene citrate with conventional gonadotrophins. Sixty clomiphene-resistant women with PCOS were randomized to two groups (n = 30 each), using computer-generated tables. Group I received metformin for 6 months, followed by ovulation induction with clomiphene citrate; group II received hMG for ovulation induction. Hormonal profiles were evaluated at the onset and after completion of treatment.. There was no significant difference in pregnancy rates between the two groups (16.7 versus 23.3%). In group I, there was a significant improvement in menstrual function and ovulation after treatment (40%, P < 0.001; and 46.7%, P < 0.001), with a significant decrease in fasting insulin levels (P < 0.05). There were no changes in other biochemical parameters. The ovulation rate in group II was 43.3%, with a high drop-out rate. The cost-effective analysis for medications per pregnancy in group I was US$ 71 +/- 3 versus US$ 277 +/- 171 in group II.. Sequential treatment with metformin and clomiphene citrate is an effective and safe option for clomiphene-resistant women with PCOS.

Topics: Adult; Clomiphene; Cost-Benefit Analysis; Drug Resistance; Drug Therapy, Combination; Fasting; Female; Fertility Agents, Female; Health Care Costs; Humans; Insulin; Menotropins; Menstruation; Metformin; Ovulation; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy; Pregnancy Rate

To evaluate the role of ketoconazole in prevention of ovarian hyperstimulation syndrome (OHSS) in women with the polycystic ovary syndrome (PCOS) undergoing ovarian stimulation with gonadotropins.. Prospective, randomized, double-blind, placebo-controlled study.. University hospitals. One hundred nine women with PCOS who were referred for treatment with gonadotropins.. Fifty patients were randomly assigned to receive two ampoules of hMG beginning on day 2 or 3 of the cycle and ketoconazole (50 mg every 48 hours) starting on the first day of hMG treatment. Fifty-one patients received the same amount of hMG plus one tablet of placebo every 48 hours.. Follicular development, E(2) level, and pregnancy rate.. The total number of hMG ampoules and duration of treatment to attain ovarian stimulation were higher among ketoconazole recipients. The serum E(2) level and number of patients with dominant follicles on day 9 of the cycle were greater in placebo recipients. Serum E(2) level and total number of follicles at the time of hCG administration did not differ between the two groups. The cancellation rate and OHSS rate were similar in the two groups.. Ketoconazole does not prevent OHSS in patients with PCOS who are undergoing ovarian stimulation. It may reduce the rate of folliculogenesis and steroidogenesis.

Topics: Adult; Androgen Antagonists; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Estradiol; Female; Fertility Agents, Female; Humans; Incidence; Infertility, Female; Ketoconazole; Menotropins; Ovarian Follicle; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Placebos; Polycystic Ovary Syndrome; Pregnancy; Pregnancy Rate; Treatment Failure

The aim of our study was to determine the efficacy of postponing administration of human chorionic gonadotropin while continuing daily gonadotropin-releasing hormone agonist therapy ('coasting') to prevent the occurrence of severe ovarian hyperstimulation syndrome (OHSS) for patients with polycystic ovary (PCO) syndrome. Five patients with PCO who had been hospitalized due to severe OHSS in previous in vitro fertilization and embryo transfer or intrauterine insemination cycles at the Tottori University Hospital were included in the study. The rates of mature oocytes and fertilization were comparable between the cycles. A singleton pregnancy was achieved in a patient during the coasting cycle, and none of the women developed severe OHSS in coasting cycles. The results suggest that coasting may be an alternative method for reducing the severity of OHSS in patients with PCO.

Topics: Adult; Buserelin; Female; Fertility Agents, Female; Humans; Menotropins; Ovarian Hyperstimulation Syndrome; Polycystic Ovary Syndrome; Reproductive Techniques

To investigate the clinical efficacy of mild inhibition of ovarian steroidogenesis by very low-dose ketoconazole during induction of ovulation in patients with polycystic ovary syndrome (PCOS).. Prospective, randomized, cross-controlled study in consecutive cycles.. Large tertiary care center.. Eighteen patients with PCOS undergoing hMG superovulation with or without ketoconazole.. A fixed hMG dosage was initiated on cycle days 5-9 in both of the study cycles. Further hMG adjustment was done according to serum E2 levels and follicular measurements. Ketoconazole was administered in one of the cycles by two protocols.. Serum E2 and P levels, lead follicles, pregnancy rate, and development of ovarian hyperstimulation syndrome.. Although higher daily hMG doses were needed in cycles with ketoconazole compared with cycles without the drug, the peak E2 levels were substantially lower in the ketoconazole cycles. Although the number of lead follicles did not differ between treatments, the addition of ketoconazole significantly reduced the number of hyperstimulated cycles. Consequently, the cancellation rate dropped dramatically, thus yielding a higher pregnancy rate per patient in the ketoconazole protocols.. Use of a very low dose of ketoconazole during ovulation induction effectively attenuates ovarian steroidogenesis in patients with PCOS. This effect may serve as an adjunct to better control the ovarian response in women who are prone to hyperstimulated cycles.

Topics: Adolescent; Adult; Cross-Over Studies; Dose-Response Relationship, Drug; Estradiol; Female; Humans; Ketoconazole; Menotropins; Menstrual Cycle; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Polycystic Ovary Syndrome; Progesterone; Prospective Studies; Superovulation

The aim of the presented study was to compare FSH threshold levels and ovarian response to stimulation with one of two standard increments of exogenous FSH above the threshold in patients with polycystic ovary syndrome (PCOS) (n = 12) and eumenorrheic women (n = 11). The individual FSH threshold was determined by treatment according to a low-dose, step-up protocol with urinary FSH (Metrodin; Ares Serono, Geneva, Switzerland). In a subsequent treatment cycle, six PCOS patients and six eumenorrheic women were randomly assigned to double-blind treatment with the threshold dose plus 1/2 ampoule; the other six PCOS patients and five eumenorrheic women were treated with 1 ampoule above the threshold dose. Determination of threshold levels showed no significant differences in median and range between PCOS patients and eumenorrheic women. The number of follicles on the day of human chorionic gonadotropin administration showed no significant correlation with the increase in FSH level above the threshold level. Irrespective of the dose given, the number of follicles in the PCOS group was significantly higher than in eumenorrheic women. The higher sensitivity for gonadotropin stimulation in patients with PCOS compared with women with regular menstrual cycles therefore appears not to be dependent on differences in FSH threshold level, but rather on the larger size of the FSH sensitive cohort of small antral follicles.

Topics: Adolescent; Adult; Chorionic Gonadotropin; Dose-Response Relationship, Drug; Double-Blind Method; Estradiol; Female; Fertility Agents, Female; Humans; Menotropins; Ovarian Follicle; Ovary; Ovulation Induction; Polycystic Ovary Syndrome

A randomised clinical trial was performed to evaluate the effect of a 3-month gonadotrophin-releasing-hormone analogue (GnRH-a) in one cycle of ovulation induction with low-dose pure follicle-stimulating hormone (pFSH) in patients with polycystic ovarian syndrome (PCOS) anovulation. Twenty patients with chronic anovulation due to PCOS were randomised to ovulation induction with pFSH administered in a low-dose schedule with (10 patients) and without (10 patients) a 3-month pretreatment with GnRH-a. Ultrasound scan only monitoring of follicular growth, evaluation of plasmatic oestradiol at the day of triggering of ovulation with human chorionic gonadotrophin 5,000 IU and evaluation of plasmatic progesterone 8 days after were the main outcome measures. Ovulation occurred in 9 patients treated with pFSH and in 2 patients treated with GnRH-a plus pFSH. Five pregnancies in the pFSH group and no pregnancy in the GnRH-a group were obtained. Five cycles were stopped due to multifollicular growth in the GnRH-a group and 1 in the pFSH group. Pretreatment with a 3-month administration of a GnRH-a did not improve the ovulation rate and pregnancy rate in PCOS patient ovulation induction with low-dose pFSH.

Topics: Adult; Anovulation; Chorionic Gonadotropin; Estradiol; Female; Humans; Menotropins; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy; Triptorelin Pamoate

To test the hypothesis that the increased ovarian sensitivity to gonadotropins observed in women with polycystic ovary syndrome (PCOS) may be due to changes in ovarian stromal blood flow in these patients.. Uterine and ovarian stromal arterial blood flow (with transvaginal color Doppler ultrasound) were measured in ten women with PCOS and 12 normo-ovulatory women (control group), undergoing gonadotropin stimulation before in vitro fertilization.. A careful ovarian stimulation strategy was adopted for the study group in order to avoid ovarian hyperstimulation syndrome and achieve an ovarian response which was comparable to that of the control group. Resistance and pulsatility indices (RI and PI) of the uterine and ovarian stromal arteries were calculated before the onset of gonadotropin treatment, on cycle day 5 (after commencing treatment), day of human chorionic gonadotropin injection, day of ovum pick-up as well as on the day of embryo transfer, and 7 and 12 days later.. No significant differences were found in RI and PI between the study and control groups throughout the treatment cycle.. It seems that polycystic ovaries do not bear an inherent disturbance in blood flow dynamics of the uterine and ovarian arteries, as measured by color Doppler, which would explain the increased sensitivity of polycystic ovaries to stimulation with gonadotropins.

Topics: Adult; Analysis of Variance; Blood Flow Velocity; Female; Fertility Agents, Female; Hemodynamics; Hormones; Humans; Menotropins; Nafarelin; Ovary; Polycystic Ovary Syndrome; Reference Values; Regional Blood Flow; Ultrasonography, Doppler, Color; Uterus

To compare the efficacy and safety of the fixed-dose, the step-down, and the low-dose step-up regimens of hMG for women with polycystic ovary syndrome (PCOS).. Prospective randomized study.. Gunma University School of Medicine, Maebashi, Japan.. Thirty-seven women with PCOS.. The fixed-dose, the step-down. and the low-dose step-up regimens were administered.. The number of growing follicles and serum hormone levels.. Serum FSH levels on the day of hCG administration were significantly higher in the fixed-dose regimen group than in the step-down and the low-dose step-up regimen groups, and the number of growing follicles (> or =11 mm) in the low-dose step-up regimen group was significantly smaller than in the fixed-dose regimen group. On the 7th day after hCG administration, the maximal diameter of the ovaries in the low-dose step-up regimen group was significantly smaller than in the fixed-dose and the step-down regimen groups, and the risk of excessive ovarian enlargement (> or =70 mm) was significantly lower in the low-dose step-up regimen group than in the fixed-dose regimen group.. The low-dose step-up regimen of hMG for patients with PCOS may be the safest protocol among the three stimulation regimens for reducing multiple follicular development.

Topics: Adult; Analysis of Variance; Dose-Response Relationship, Drug; Female; Hormones; Humans; Menotropins; Ovarian Follicle; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy; Pregnancy Outcome; Pregnancy Tests; Ultrasonography

The aim of this study was to evaluate the ovarian cysts appearing during GnRH-a/hMG treatment in patients with polycystic ovarian syndrome (PCOS). A total of 35 women with PCOS were included in the study. All women received 3.75 mg IM of long-acting leuprolide acetate on the first day of the menstrual cycle. On the 15th day of the menstrual cycle, transvaginal ultrasound examination (US) and determination of serum E2 were done. A total of 90 cycles were studied in this way and during these cycles, 14 (15.5%) ovarian cysts with a diameter of >/= 20 mm developed. According to the serum E2 levels, 11 cases (group A) had E2 concentrations > 35 pg/ml and 3 (group B) had serum E2 levels < 35 pg/ml. Group A patients attained a significantly larger mean size of ovarian cyst than group B patients (42 +/- 7.3 vs. 24.2 +/- 3.2 mm, p < 0.001). When the serum E2 concentrations were < 35 pg/ml, the ovarian cysts were disregarded and ovarian stimulation with gonadotropins was initiated. In case that serum E2 levels were > 35 pg/ml, the initiation of the ovarian stimulation with hMG was postponed until serum E2 levels indicated down-regulation, which was achieved after 5.8 +/- 2.9 days. In both groups the ovarian stimulation resulted in ovulatory cycles, while four pregnancies in group A and one in group B were achieved. In conclusion, our results indicate that in patients with PCOS the GnRH-a administration may cause follicular cysts at an incidence of 15.5%. These cysts do not constitute a contraindication for ovarian stimulation provided that serum E2 levels are low.

Topics: Adult; Estradiol; Female; Humans; Infertility, Female; Leuprolide; Menotropins; Ovarian Cysts; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy

Fifty women with polycystic ovaries took part in a prospective randomized study. All women required treatment by in-vitro fertilization (IVF) for reasons other than anovulation. They had all previously undergone ovarian stimulation with gonadotrophin therapy which had failed to result in pregnancy or had been abandoned due to high risk of developing ovarian hyperstimulation syndrome (OHSS). Twenty-five women were treated by long-term pituitary desensitization followed by gonadotrophin therapy, oocyte retrieval and embryo transfer (group 1). Twenty-five women underwent laparoscopic ovarian electrocautery after pituitary desensitization followed by gonadotrophin therapy, oocyte retrieval and embryo transfer (group 2). A significantly higher number of women in group 1 had to have the treatment cycle abandoned due to impending or actual OHSS, determined by endocrine and clinical findings. In addition, the development of moderate or severe OHSS in completed cycles was higher in group 1. The pregnancy rate and miscarriage rates in the two treatment groups were similar. The authors propose that laparoscopic ovarian electrocautery is a potentially useful treatment for women who have previously had an IVF treatment cycle cancelled due to risk of OHSS or who have suffered OHSS in a previous treatment cycle.

Topics: Abortion, Spontaneous; Adult; Electrocoagulation; Embryo Transfer; Estradiol; Female; Fertilization in Vitro; Humans; Laparoscopy; Menotropins; Ovarian Hyperstimulation Syndrome; Ovary; Polycystic Ovary Syndrome; Pregnancy; Prospective Studies

To study ovarian stimulation and response patterns during a gonadotropin step-down dose regimen for induction of ovulation by applying a decremental dose regimen in polycystic ovary syndrome (PCOS) patients.. The present prospective study involves 28 infertile clomiphene citrate-resistant PCOS patients during gonadotropin-induced cycles using a modified step-down dose regimen (and adjuvant GnRH agonist medication). Applied gonadotropin doses included initial daily doses of 150 IU IM followed by two reducing steps (37.5 IU each) based on sonographic criteria to a final daily dose of 75 IU IM.. Anovulatory infertile women in an academic referral center.. Daily blood withdrawal and transvaginal pelvic ultrasound.. Serum FSH and E2 concentration and follicle growth were investigated daily during gonadotropin administration.. An initial 2.1-fold increase in serum FSH levels was observed followed by a subsequent decrease of 10% (median) per day for 4 days. Growth of ovarian follicles was sustained and ovulation achieved (midluteal P, 11.7 +/- 1.3 ng/mL; conversion factor to SI unit, 3.180; mean +/- SD) in 22 patients. Major variability in day 3 E2 increase (range, 67 to 866 pg/mL; conversion factor to SI unit, 3.671)--not related to differences in FSH serum concentrations and without changes in follicle number and size--suggests differences in ovarian sensitivity for FSH stimulation. A strong correlation (r = 0.82) was found between day 3 E2 increase and the chance of ovulation. Moreover, E2 levels on the day of gonadotropin dose reduction predict (r = 0.68) chances of late follicular phase E2 levels exceeding 871 pg/mL (conversion factor to SI value, 3.671).. These findings provide the endocrine basis for the concept of gonadotropin induction of ovulation using a step-down dose regimen. Initial E2 increase (before initiation of follicle growth) represent differences in ovarian sensitivity to gonadotropins and predict treatment outcome.

Topics: Buserelin; Chorionic Gonadotropin; Estradiol; Female; Follicle Stimulating Hormone; Humans; Infertility, Female; Menotropins; Ovulation Induction; Polycystic Ovary Syndrome; Prospective Studies

To examine the null hypothesis that women with polycystic ovary syndrome (PCOS) produce similar levels of prorenin and other components of the ovarian-derived prorenin to angiotensin cascade (ODPAC) at baseline and after stimulation with clomiphene citrate (CC) or hMG when compared with normal age- and weight-matched ovulatory controls.. Prospective controlled clinical trial.. Infertility clinic in a university-based county hospital and a hospital-based private infertility practice.. Twenty-eight infertile women aged 18 to 35 years. Thirteen patients were diagnosed with PCOS. Fifteen normal ovulatory patients who were matched for age and weight served as controls.. Twenty patients were stimulated with CC and eight were stimulated with hMG.. Serum E2, P, T, androstenedione (A), DHEAS, LH, FSH, and plasma prorenin, active renin, and angiotensin II (Ang II) were measured at baseline and during the preovulatory and midluteal phases of the stimulation cycles.. Baseline plasma prorenin in PCOS was higher than that of follicular phase controls. Plasma prorenin correlated significantly with peripheral androgen levels. Prorenin, active renin, and Ang II increased in response to gonadotropins with the largest increases occurring in control patients receiving CC. An association was seen between ovulation with CC and lower baseline levels of active renin.. The null hypothesis was rejected. Infertile women with PCOS have higher baseline prorenin levels when compared with age- and weight-matched ovulatory controls. There is a significant correlation between prorenin and the peripheral levels of androgens produced during ovarian stimulation. Baseline active renin levels may be predictive of ovulation with CC.

Topics: Adolescent; Adult; Androstenedione; Angiotensin II; Clomiphene; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Enzyme Precursors; Female; Humans; Hyperandrogenism; Infertility, Female; Matched-Pair Analysis; Menotropins; Ovulation Induction; Polycystic Ovary Syndrome; Prospective Studies; Renin; Testosterone

To evaluate the efficacy and tolerability of treatment with goserelin + HMG vs bromocriptine + FSH + HMG in the induction of ovulation in patients with ovarian polycystosis.. A randomized prospective study.. Sterile women with ovarian polycystosis of the first type not responding to clomiphene citrate.. Group A: bomocriptine + FSH + HMG (10 patients); Group B: goserelin depot (Zoladex) + HMG (18 patients).. A greater percentage of ovulations, pregnancies and a higher success rate were obtained in Group B. The percentage of hyperstimulation was similar in both groups; there was a higher percentage of abortion in Group A. Cycle duration and the number of phials of gonadotropin were greater in Group B.. Treatment with bromocriptine + gonadotropin remains the simplest; the treatment protocol based on geserelin depot + gonadotropin proved to be more efficacious.

Topics: Adult; Bromocriptine; Clinical Protocols; Dose-Response Relationship, Drug; Female; Follicle Stimulating Hormone; Goserelin; Humans; Infertility, Female; Menotropins; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy; Pregnancy Complications; Pregnancy Outcome

Our purpose was to examine the efficacy of laser vaporization of the ovarian surface in polycystic ovary disease to reduce repeated ovarian hyperstimulation syndrome and thereby improve pregnancy outcome.. Twenty-six infertile patients with polycystic ovary disease who previously had ovarian hyperstimulation syndrome after stimulation with human menopausal gonadotropin and who failed to conceive were studied. All patients were treated by potassium titanyl phosphate and neodymium-yttrium-aluminum-garnet laser and evaluated. Patients not ovulating spontaneously after vaporization were treated with either clomiphene citrate or human menopausal gonadotropin.. After vaporization spontaneous ovulation was confirmed in six patients. For ovulation induction three patients received clomiphene citrate and 17 received human menopausal gonadotropin. Of the patients treated with human menopausal gonadotropin, mild ovarian hyperstimulation syndrome was found in three patients, and the incidence of ovarian hyperstimulation syndrome decreased significantly. Pregnancy was confirmed in 19 of 26 patients.. Laser vaporization is promising for the prevention of ovarian hyperstimulation syndrome and improving pregnancy outcome in patients with polycystic ovary disease who have previously had ovarian hyperstimulation syndrome.

Topics: Adult; Clomiphene; Female; Follicle Stimulating Hormone; Humans; Laser Therapy; Luteinizing Hormone; Menotropins; Ovarian Hyperstimulation Syndrome; Polycystic Ovary Syndrome; Pregnancy; Pregnancy Outcome

To evaluate the outcome of oocytes donated by women with polycystic ovarian syndrome (PCOS) compared with oocytes donated by women with mechanical infertility.. A retrospective study.. The outcome of 159 oocyte donation cycles with oocyte donated by PCOS patients were compared with 69 oocyte donation cycles with oocytes donated by patients with mechanical infertility. We compared the stimulation protocols in the donors to assess if the combination of GnRH analogue (GnRH-a), FSH, and hMG has an advantage over FSH and hMG alone with respect to their effect on fertilization and implantation rates in oocyte donation cycles.. When treated with GnRH-a, pregnancy rates in PCOS and mechanical infertility donors were higher than those treated with FSH and hMG alone. The comparison between PCOS and mechanical factor oocyte recipients revealed no significant difference in the pregnancy and abortion rates, but the oocytes of patients with PCOS that were exposed to GnRH-a had a significantly higher implantation rate than those not exposed to GnRH-a.. Oocytes obtained from PCOS patients had a fertilization potential equal to oocytes obtained from mechanical infertility donors. Furthermore, because the oocytes of patients with PCOS exposed to GnRH-a had a significantly higher implantation rate, a detrimental role of high LH on oocyte quality seems probable. However, because PCOS has a high familial prevalence, some reservations may arise due to a possible propagation of the problem in the next generation of oocyte donation programs.

Topics: Embryo Implantation; Female; Fertilization in Vitro; Follicle Stimulating Hormone; Humans; Infertility, Female; Menotropins; Oocyte Donation; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy; Retrospective Studies; Triptorelin Pamoate

The elevated luteinizing hormone (LH) and androgen concentrations characteristic of women with polycystic ovaries (PCO) are considered crucial factors in their infertility. The somatostatin analogue octreotide lowers LH and androgen concentrations in women with PCO. The effects of octreotide given concurrently with human menopausal gonadotrophin (HMG) were therefore compared with that of HMG alone in 28 infertile women with PCO resistant to clomiphene. In 56 cycles of combined HMG and octreotide therapy there was more orderly follicular growth compared with the multiple follicular development observed in 29 cycles in which HMG was given alone (mean number of follicles > 15 mm diameter on the day of human chorionic gonadotrophin (HCG) administration: 2.5 +/- 0.2 and 3.6 +/- 0.4 respectively; P = 0.026). There was a significantly reduced number of cycles abandoned (> 4 follicles > 15 mm diameter on day of HCG) in patients treated with octreotide+HMG, so that HCG had to be withheld in only 5.4% of cycles compared to 24.1% with HMG alone (P < 0.05). The incidence of hyperstimulation was also lower on combined treatment. Octreotide therapy resulted in a more 'appropriate' hormonal milieu at the time of HCG injection, with lower LH, oestradiol, androstenedione and insulin concentrations. Although growth hormone concentration was similar on both regimens, significantly higher insulin growth factor-I concentrations were observed on the day of HCG in women on combined therapy than on HMG alone.

Topics: Adult; Chorionic Gonadotropin; Female; Follicle Stimulating Hormone; Gonadal Steroid Hormones; Humans; Infertility, Female; Insulin; Luteinizing Hormone; Menotropins; Octreotide; Ovarian Hyperstimulation Syndrome; Ovulation; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy

The objective of this study was to explore the effect of cotreatment with recombinant human growth hormone (GH), gonadotrophin-releasing hormone agonist (GnRHa) and human menopausal gonadotrophin (HMG) for induction of ovulation in women with clomiphene resistant polycystic ovary syndrome (PCOS). It was designed as a randomized, double-blind, placebo controlled trial in which 30 women with anovulation associated with PCOS who were resistant to clomiphene all received DTRP6-LHRH (Decapeptyl microcapsules, 3.75 mg, i.m.) and, 2 weeks later, HMG in a standard, conventional, individually adjusted dose regimen until human chorionic gonadotrophin (HCG) and then luteal phase support could be given. From day 1 of HMG therapy, patients were randomized to receive either human GH (Norditropin, 12 IU/day, i.m., for 7 days) or placebo. The number of ampoules, duration of treatment and daily effective dose of HMG required to achieve ovulation, serum oestradiol concentrations and number of follicles induced, ovulation and pregnancy rates, serum insulin and insulin-like growth factor-I (IGF-I) concentrations were measured. There were no significant differences between growth hormone and placebo groups in any of the outcomes measured, other than a growth hormone induced increase in serum insulin and IGF-I levels. We conclude that although GH kinetics are abnormal and GH pituitary reserves generally low in women with PCOS, adjuvant GH treatment to GnRHa/HMG does not influence follicular development or sensitivity in response to gonadotrophins and that it does not seem likely to be of any potential clinical benefit for the treatment of PCOS.

Topics: Adult; Chorionic Gonadotropin; Double-Blind Method; Female; Gonadotropins, Pituitary; Growth Hormone; Humans; Infertility, Female; Insulin; Insulin-Like Growth Factor I; Menotropins; Ovulation Induction; Placebos; Polycystic Ovary Syndrome; Pregnancy; Recombinant Proteins; Triptorelin Pamoate

The aim of the study was to evaluate ovarian response to gonadotrophin stimulation, with and without premedication with gonadotrophin-releasing hormone (GnRH) agonist, in patients with polycystic ovary syndrome. In all, 40 women included in the in-vitro fertilization/embryo transfer programme were divided into two groups. In the first group, buserelin, 500 micrograms/day s.c., was given until pituitary desensitization was achieved. Ovarian stimulation was performed by the combination of GnRH agonist and human menopausal gonadotrophin (HMG). The second group was treated using a conventional HMG and human chorionic gonadotrophin (HCG) protocol. Desensitization was achieved in 15.2 +/- 6.3 days (mean +/- SD) and the luteinizing hormone:follicle stimulating hormone ratio decreased from 2.84 +/- 1.54 to 0.60 +/- 0.35. Comparing the duration of stimulation, the number and size of all observed and aspirated follicles, oocytes recovered and fertilized and the number of embryos replaced, no statistically significant differences were found between the groups. The average oestradiol concentration on the day of HCG administration was lower in the group treated with premedication (P < 0.05). These data suggest that short pre-treatment with GnRH agonist can temporarily correct endocrine abnormalities of polycystic ovary syndrome but do not change the ovarian response to gonadotrophin stimulation and multiple follicular development.

Topics: Adult; Buserelin; Chorionic Gonadotropin; Embryo Transfer; Estradiol; Female; Fertilization in Vitro; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Luteinizing Hormone; Menotropins; Ovarian Follicle; Polycystic Ovary Syndrome

Luteinising hormone (LH) is essential for steroidogenesis and folliculogenesis. In hyperandrogenic patients, however, an increased androgen production with the consecutive development of polycystic ovaries is caused by elevated LH levels. Suppression of androgens by the use of a GnRH agonist (a) may be a causal therapeutic approach. Therefore, we initiated a study comparing the combined GnRHa/HMG stimulation with HMG alone in hyperandrogenic patients undergoing in-vitro fertilisation (IVF). Altogether, 62 cycles were treated. Group 1 (n = 33) received a single depot injection of 3.6 mg goserelin on cycle day 22 followed by individualised HMG stimulation 14 days later. Group 2 (n = 29) started with the HMG stimulation on cycle day 3. In group 1, a pregnancy rate per transfer of 36.4% was achieved compared to only 20% in group 2. There was a strikingly lower abortion rate in group 1 that resulted in a significantly higher on going pregnancy rate. The results are in favour of the combined GnRHa/HMG stimulation as a first line therapy for hyperandrogenic IVF patients.

Topics: Adult; Androgens; Delayed-Action Preparations; Drug Administration Schedule; Embryo Transfer; Female; Fertilization in Vitro; Goserelin; Humans; Injections, Subcutaneous; Menotropins; Polycystic Ovary Syndrome; Pregnancy; Pregnancy Outcome

The choice of treatment for clomiphene-resistant anovulation associated with polycystic ovary syndrome (PCOS) is presently arbitrary and selection criteria are not available. A total of 144 women with anovulatory infertility associated with PCOS who failed to conceive on clomiphene were treated with either pure follicle stimulating hormone (FSH) (n = 29), or human menopausal gonadotrophin (HMG) (n = 60), or gonadotrophin-releasing hormone analogue (GnRHa) and HMG (n = 55). Analysis of 306 treatment cycles and 53 pregnancies revealed a cumulative conception rate at 4 months of 23% with FSH, 47% with HMG and 69% with GnRHa + HMG. The miscarriage rate was highest in the HMG group (44%) and consequently the cumulative live birth rate was superior when GnRHa was used in combination with HMG. There were no significant differences in the basal clinical and endocrinological features of those who conceived compared with those who did not, either in the whole group, or in the individual treatment groups. Thus, the choice of treatment for clomiphene-resistant women with PCOS cannot be guided by the basal clinical or endocrinological features of this heterogeneous syndrome with the present state or knowledge.

Topics: Adult; Anovulation; Clomiphene; Drug Therapy, Combination; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Menotropins; Ovulation Induction; Polycystic Ovary Syndrome; Retrospective Studies; Treatment Failure; Triptorelin Pamoate

Using a randomized double-blind cross-over design, the pharmaco-dynamic and pharmaco-kinetic properties of 'pure' follicle-stimulating hormone (FSH) (Metrodin) and human menopausal gonadotrophin (HMG) (Pergonal) were studied in 24 women with polycystic ovary-like disease (PCOD) during induction of ovulation. Fifty-six cycles were stimulated with FSH and 60 cycles with HMG, according to a standard protocol. Gonadotrophins were administered i.v. in a pulsatile fashion using pulse frequencies of either 30 or 120 min. The cycles stimulated with either 30 or 120 min pulse intervals showed no differences among themselves. During the stimulation phase, the FSH and HMG stimulated cycles showed equal and dose dependent FSH concentrations (mean +/- SD). The luteinizing hormone (LH) concentrations (mean +/- SD) were also equal but unchanged compared to the mean basal concentration. The LH, FSH, total urinary oestrogen excretion, and testosterone profiles (mean +/- SD) obtained from cycle days -10 to 0 as well as the pregnanediol profiles obtained from cycle days 0 to +14 showed no differences either. The occurrence of an endogenous preovulatory LH surge was significantly more frequent in the cycles stimulated with a pulse interval of 30 min compared to the cycles stimulated with a pulse interval of 120 min. The addition of LH as provided in HMG did not influence the FSH threshold concentration above which initiation of follicular growth occurred, since no differences were found in the FSH 'stable' concentrations between FSH and HMG stimulated cycles. However, intra- and inter-individual variation in the FSH 'stable' concentration at which follicular growth was initiated became obvious.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Double-Blind Method; Estrogens; Female; Follicle Stimulating Hormone; Humans; Injections, Intravenous; Luteal Phase; Luteinizing Hormone; Menotropins; Ovarian Follicle; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Polycystic Ovary Syndrome; Secretory Rate; Testosterone

To compare the effect of ovarian electrocautery versus an intranasal (IN) luteinizing hormone-releasing hormone agonist (LH-RH-a) in the response of patients with polycystic ovarian disease (PCOD) to human menopausal gonadotropin (hMG) therapy.. A prospective study with serial randomization of patients in two groups for treatment with ovarian electrocautery + hMG or LH-RH-a + hMG.. A teaching hospital reproductive endocrinology clinic.. Thirty-three women with PCOD who failed to conceive after six treatment cycles with hMG.. Midcycle and luteal phase endocrinology, ovulation, pregnancy rates (PRs), and miscarriage rates.. There was no difference in the ovulation or PRs between the two groups. However, the number of cycles with multiple dominant follicles, the luteal phase serum testosterone, and the miscarriage rate were lower in the group pretreated with ovarian electrocautery.. Pretreatment of patients with PCOD with ovarian electrocautery may be a better alternative to IN LH-RH-a therapy for induction of ovulation with hMG.

Topics: Administration, Intranasal; Adult; Buserelin; Electrocoagulation; Female; Gonadotropin-Releasing Hormone; Humans; Luteinizing Hormone; Menotropins; Ovary; Ovulation; Polycystic Ovary Syndrome; Pregnancy; Testosterone

To assess the levels of cytokines in the follicular fluid of stimulated ovaries.. The study included two groups of four patients with polycystic ovarian disease. These were diagnosed by clinical and ultrasonic features and characteristic hormonal profiles, treated with gonadotropin-releasing hormone-analogue and human menopausal gonadotropin. One group received dexamethasone (DEX).. Dexamethasone is capable of directly affecting granulosa and immune cells. It was also expected to affect cytokine production of granulosa and immune cells of the ovary.. This study demonstrates that FF from patients treated with DEX has reduced tumor necrosis factor (TNF) activity and elevated colony-stimulating factor levels. Regardless of the treatment with DEX, the follicles with high levels of TNF contained minimal concentrations of estradiol. Interleukin-6 did not differ between the FF samples.. These results suggest a role for cytokines in the process of folliculogenesis and ovarian maturation. Modification of cytokines by DEX might explain the beneficial effect of fertility.

Topics: Colony-Stimulating Factors; Cytokines; Delayed-Action Preparations; Dexamethasone; Estradiol; Female; Gonadotropin-Releasing Hormone; Humans; Interleukin-6; Menotropins; Ovarian Follicle; Polycystic Ovary Syndrome; Probability; Progesterone; Triptorelin Pamoate; Tumor Necrosis Factor-alpha

To explore the effect of cotreatment with growth hormone (GH) for ovarian stimulation after pituitary suppression.. A randomized, double-blind, placebo-controlled study.. Specialist Reproductive Endocrine and In Vitro Fertilization (IVF) Unit.. Twenty-five IVF patients who had responded suboptimally in a previous treatment cycle. A subgroup of 18 patients were found to have ultrasound (US) findings of polycystic ovaries (PCO).. The amount of gonadotropin used, development of follicles greater than or equal to 14 mm, number of oocytes collected, fertilized, cleaved and replaced, serum and follicular fluid (FF) insulin-like growth factor I (IGF-I) concentrations.. Cotreatment with GH was associated with a significant reduction in gonadotropins requirement (P less than 0.05). In patients with US-diagnosed PCO more follicles developed (P less than 0.05), more oocytes were collected (P less than 0.03), fertilized (P less than 0.004), and cleaved (P less than 0.02). A significantly higher FF IGF-I concentrations were found in patients receiving cotreatment with GH compared with those who received placebo (P less than 0.04).. We believe that there may be a place for GH treatment in selected IVF cycles after pituitary suppression but what the role of IGF-I should further be investigated.

Topics: Adult; Double-Blind Method; Drug Therapy, Combination; Female; Fertilization in Vitro; Follicular Fluid; Growth Hormone; Humans; Insulin-Like Growth Factor I; Menotropins; Ovary; Pituitary Gland; Placebos; Polycystic Ovary Syndrome; Pregnancy; Pregnancy Outcome; Ultrasonography

Since patients with polycystic ovary syndrome (PCOS) commonly have insulin resistance, albeit with normal glucose tolerance, we evaluated glucose tolerance in PCOS patients exposed to the diabetogenic effect of pregnancy. The clinical material was obtained from two centers, in Springfield, Illinois (22 patients), and New York, New York (31 patients), and the results were compared with a control population with 2,306 consecutive general pregnancies. There were no differences between PCOS patients from the two centers in regard to age or ponderal index (P greater than .1). A review of the medical records showed that the incidence of gestational diabetes in the PCOS patients was 7.5%, similar (P greater than .1) to the 6.6% frequency of gestational diabetes in the controls. The overall incidence of neonatal macrosomia (birth weight greater than 4,000 g) was 7% (4 of 57) among infants born to PCOS women. That was similar to the 12.4% incidence of neonatal macrosomia among infants born to women with normal glucose tolerance and to the 14.5% incidence among infants born to women with gestational diabetes. Preexisting PCOS does not appear to increase the risk of developing gestational diabetes or neonatal macrosomia.

Topics: Adult; Clomiphene; Dexamethasone; Female; Fetal Macrosomia; Glucose Tolerance Test; Humans; Infant, Newborn; Infertility, Female; Menotropins; Polycystic Ovary Syndrome; Pregnancy; Pregnancy in Diabetics; Retrospective Studies

Treatment with low-dose follicle-stimulating hormone (FSH) is associated with a high rate of ovulation in anovulatory women with polycystic ovarian syndrome (PCOS), but it is not clear whether the success of treatment is because of the use of pure FSH or the low dose of gonadotropin. We undertook a randomized controlled study to compare the effects of urinary FSH and human menopausal gonadotropin (hMG) using a low-dose regimen in 30 women with PCOS. Each subject received a maximum of three cycles of either FSH or hMG. Ovulation occurred in 75% of subjects and in 77% of cycles induced with FSH and in 94% of women, 85% of cycles of those treated with hMG. A single dominant follicle developed in 70% (FSH) and 65% (hMG) of cycles, respectively. Five singleton pregnancies occurred in each group. This study shows that low-dose FSH and hMG are equally successful in inducing ovulation, suggesting that the success of treatment depends on the low dose of gonadotropin used rather than the presence or absence of luteinizing hormone in the preparation.

Topics: Abortion, Spontaneous; Female; Follicle Stimulating Hormone; Humans; Luteinizing Hormone; Menotropins; Polycystic Ovary Syndrome; Pregnancy; Random Allocation

Seventy-two infertile women with polycystic ovary disease (PCOD) and clomiphene citrate treatment failure underwent 220 human menopausal gonadotropin (hMG) and human chorionic gonadotropin (hCG) treatment cycles for ovulation induction over a period of 19 months. Forty-two patients ovulated but failed to conceive on clomiphene, and the remaining 30 failed to ovulate on clomiphene. Monitoring of treatment consisted of serum 17 beta-estradiol (E2) levels and ultrasonic assessment of follicular growth. Treatment was withheld whenever the E2 levels exceeded 1,500 pg/mL and/or when more than two follicles greater than or equal to 17 mm in diameter each were encountered on ultrasonography. Twenty-nine patients conceived (40.2%), and 23 delivered viable infants. Twenty-three of the 29 pregnancies were achieved in the 42 patients who ovulated on clomiphene, while only 6 pregnancies resulted in the 32 anovulatory patients on clomiphene. Six patients (20.6%) aborted in the first trimester. Multiple pregnancies consisted of only two sets of twins (6.9%). There were only two cases of mild hyperstimulation (2.7%) and no severe hyperstimulation. Because of the low occurrence of multiple pregnancies and hyperstimulation and the reasonable success rate, all PCOD patients should be started on this protocol.

Topics: Adult; Chorionic Gonadotropin; Clomiphene; Estradiol; Female; Humans; Infertility, Female; Menotropins; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy; Pregnancy Outcome

In a prospective study, 140 patients with infertility because of ovulatory factors (group A) were followed up for 6 months after failure to achieve pregnancy using human menopausal gonadotropin (hMG) therapy. They included cases of oligomenorrhea, polycystic ovarian disease (PCOD), and hypogonadotropic amenorrhea. They were treated with hMG alone or in combination with clomiphene citrate or gonadotropin-releasing hormone agonist analog. The control group (B) included 83 infertile patients because of similar ovulatory factors. They were followed up for 6 months not preceded by ovulation induction. The overall pregnancy rate (PR) in group A (20.7%) was significantly higher than group B (7.2%). The PR was significantly higher in oligomenorrhea and PCOD patients when compared with the control group. There was no significant difference in the hypogonadotropic group.

Topics: Anovulation; Female; Humans; Infertility, Female; Menotropins; Menstruation Disturbances; Polycystic Ovary Syndrome; Pregnancy; Prospective Studies

A randomized, double-blind, crossover study was carried out to compare purified urinary follicle-stimulating hormone (FSH) and human menopausal gonadotropin (hMG) for ovarian stimulation in polycystic ovarian syndrome (PCOS). Twelve patients were stimulated with FSH and hMG in three alternate cycles. FSH, luteinizing hormone (LH), estradiol, dihydroepiandrosterone sulphate, free and total testosterone, delta 5-androstenedione, sex hormone binding globulin, and ovarian volume were monitored during the stimulation. There was no difference between the dose of FSH and hMG necessary to induce preovulatory follicles in the individual patients. The mean increase of ovarian volume during stimulation with FSH and hMG was 120% and 129% respectively (no significant difference). Two patients became pregnant in the first cycle. Two other patients had delayed bleeding and positive serum-human chorionic gonadotropin. No significant difference was found in the endocrine changes during the two different stimulation methods. The LH/FSH ratio was normalized after a few days of treatment regardless of the type of stimulation. The size of the material does not permit a comparison of the efficacy of the two treatment schedules. Our clinical and ultrasonic observations do not support the theory that treatment of infertility in PCOS with FSH is more safe than with hMG.

Topics: Estradiol; Female; Follicle Stimulating Hormone; Humans; Luteinizing Hormone; Menotropins; Ovary; Ovulation; Ovulation Induction; Polycystic Ovary Syndrome; Ultrasonography

This study was designed to compare the results of treatment with, firstly, exogenous gonadotrophins, with (57 cycles) and without (65 cycles) pretreatment with a superactive analogue of luteinizing hormone releasing hormone (LHRH) and, secondly, pure follicle stimulating hormone (FSH) (50 cycles) with those of human menopausal gonadotrophin (HMG) (72 cycles) in 46 women with clomiphene-citrate-resistant anovulation associated with polycystic ovaries. Patients randomly allocated to the analogue group received buserelin (Suprefact, Hoechst, UK, Ltd, Hounslow, Middlesex), 800 micrograms/day by nasal insufflation and when hypogonadism was achieved, patients were again randomly allocated for ovarian stimulation with either FSH or HMG. Controls received FSH or HMG alone. Patients pretreated with the analogue had similar pregnancy and ovulation rates, needed larger doses and more days of gonadotrophin therapy and had more ovarian overstimulation than those receiving no pretreatment. The role of superactive LHRH analogues for induction of a single ovulation for in-vivo fertilization is thus uncertain. Pure FSH had no advantages over HMG, the LH content of HMG having no deleterious effect on the ovary.

Topics: Adult; Chorionic Gonadotropin; Drug Therapy, Combination; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Gonadotropins; Humans; Infertility, Female; Menotropins; Ovulation Induction; Polycystic Ovary Syndrome

Little data exist on the effects of adjunctive therapy with leuprolide acetate (LA) in the luteal phase of women with polycystic ovary syndrome (PCOS) undergoing ovulation induction with human menopausal gonadotropin (hMG). Additionally, it is not known whether gonadal steroid concentrations in the luteal phase of induced cycles in PCOS are predictive of pregnancy. In this prospective, randomized study comparing cycles using hMG alone (n = 26) with cycles using hMG with LA (n = 33), no differences were noted between treatment groups in progesterone (P), estradiol (E2), and P:E2 ratios on luteal days 3, 6, and 9. When all treatment cycles were pooled, there were no differences in P, E2, or P:E2 ratios, comparing conception and nonconception cycles. We conclude that adjunctive therapy with LA in PCOS patients undergoing ovulation induction with hMG does not alter the luteal phase concentrations of P, E2, and P:E2. Furthermore, no correlation was found between the serum concentrations of these luteal phase steroids and cycle fecundity.

Topics: Drug Therapy, Combination; Estradiol; Female; Gonadotropin-Releasing Hormone; Humans; Infertility, Female; Leuprolide; Luteal Phase; Menotropins; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy; Progesterone; Prospective Studies; Random Allocation

Combined treatment with pulsatile LH-RH and hMG, given to eight patients who had anovulation associated with PCO and resistant to CC, significantly reduced the number of large follicles induced by hMG alone. A direct effect of pulsatile LH-RH on the ovary is postulated. This combined treatment eased the problems of multifollicular development, thereby increasing efficiency and reducing complications in patients with PCO stimulated by gonadotropins.

Topics: Female; Gonadotropin-Releasing Hormone; Gonadotropins; Humans; Hypophysectomy; Menotropins; Ovarian Follicle; Ovary; Polycystic Ovary Syndrome; Pregnancy; Pulsatile Flow

Eighty-eight clomiphene citrate-resistant infertile patients with oligomenorrhoea or amenorrhoea attributable to polycystic ovarian disease were divided at random into three groups. Twenty-nine patients were treated with ovarian electrocautery, 30 with human menopausal gonadotrophins (hMG) and 29 with pure follicle stimulating hormone (FSH). Successful ovulation was induced in 71.4, 70.6 and 66.7% of the cycles in the groups respectively. Ten patients conceived after electrocautery and pure FSH therapy while 15 conceived after hMG medication (chi-squared = 1.6464, P = 0.439). The six-cycle cumulative pregnancy rate in the three consecutive groups was 52.1, 55.4, and 38.3%. Four further pregnancies were achieved after treating 10 patients in the electrocautery group with clomiphene citrate (100 mg/day for 5 days) for 25 cycles. The rate of pregnancy wastage in the corresponding groups was 21.4, 53.3 and 40% (chi-squared = 3.127, P = 0.2039). Ovarian electrocautery is equally effective as hMG and pure FSH in the treatment of PCO patients resistant to clomiphene citrate therapy.

Topics: Adult; Drug Therapy, Combination; Electrocoagulation; Female; Follicle Stimulating Hormone; Humans; Infant, Newborn; Menotropins; Ovary; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy; Pregnancy Outcome

The present study was undertaken to verify the efficacy of preparations for inducing follicular maturation and ovulation in patients with polycystic ovary syndrome (PCOS). Successful induction of ovulation in patients with PCOS was observed in treatment cycles with daily injections or pulsatile subcutaneous administration of human menopausal gonadotropin (hMG), the combination of clomiphene citrate and bromocriptine, or the combination of clomiphene citrate and hMG. The incidence of ovarian hyperstimulation syndrome varied with the different clinical conditions in which ovulation was induced, the types of preparations administered, and the doses and schedules administered.

Topics: Bromocriptine; Buserelin; Clomiphene; Drug Therapy, Combination; Female; Gonadotropin-Releasing Hormone; Humans; Menotropins; Ovarian Diseases; Ovarian Follicle; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy

The present study was undertaken to determine whether ovulation can be induced in patients with polycystic ovary syndrome (PCOS) by pulsatile subcutaneous administration of hMG after the pituitary secretion of LH and FSH was suppressed with a gonadotropin releasing hormone (GnRH) analogue. The results of the combined regimen cycles (group II) were compared with those of hMG (group I) or FSH (group III) pulsatile administration in the same PCOS patients. The ovulation rate (89.1% of 46 cycles) in group I was significantly greater (p less than 0.01) than that found in group II (65.9% of 41 cycles). In group III, ovulation occurred in 89.5% of the 19 treatment cycles. Ovarian hyperstimulation syndrome (OHSS) occurred in 28.3% of cycles in group I, 7.3% in group II, and 26.3% in group III, respectively. The incidence of OHSS in group II was significantly lower than that found in group I or III. The rates of pregnancy were 10.9% of cycles in group I, 4.9% in group II, and 21.1% in group III, respectively. All 10 fetuses were singleton conceptions, and the pregnancies continued successfully to term. The present data demonstrate that pulsatile subcutaneous administration of hMG or FSH is effective in the induction of successful ovulation and the establishment of singleton pregnancy in patients with PCOS.

Topics: Adult; Buserelin; Drug Therapy, Combination; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Luteinizing Hormone; Menotropins; Ovarian Diseases; Ovulation Induction; Periodicity; Pituitary Gland; Polycystic Ovary Syndrome; Pregnancy

We performed a pharmacodynamic comparison of human urinary follicle-stimulating hormone (hFSH) and human menopausal gonadotropin (hMG) to characterize differences in the bioavailability of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), as well as to compare estrogen responses in normal women and those with polycystic ovary syndrome (PCOS). Ten women with PCOS and ten normal ovulatory controls were randomized to receive a single dose (2 ampules) of either hFSH or hMG. Serum LH decreased significantly following hFSH with responses occurring earlier in controls (24.5 +/- 10.9% after 30 minutes) than in PCOS patients (27.3 +/- 7.5% after 18 hours). After hMG, LH increased only in controls (33.8 +/- 16.3%). An FSH increment following hFSH was observed in both PCOS patients (54.7 +/- 24.8%) and controls (74.6 +/- 36.8%), with peak responses at 6 and 4 hours, respectively. However, after hMG, FSH increased only in controls. The LH/FSH ratio after hFSH decreased, with the nadir at 18 hours (1.438 +/- 0.183) being similar to baseline LH/FSH ratios of controls (1.433 +/- 0.341). Serum estradiol (E2) increased following hMG, with peak responses after 18 hours, in both PCOS patients (75.4 +/- 28.6%) and controls (88.5 +/- 32.5%). The peak E2 response to hFSH was observed to be earlier in PCOS patients (147 +/- 34%), occurring after 12 hours, compared with controls (58 +/- 29% after 18 hours).

Topics: Adult; Biological Availability; Estradiol; Female; Follicle Stimulating Hormone; Humans; Luteinizing Hormone; Menotropins; Polycystic Ovary Syndrome; Reference Values

Treatment with a combination of luteinizing hormone-releasing analogue (GnRHa, Buserelin) and pulsatile administration of hMG (Group I) were used to induce ovulation in nine patients with polycystic ovary syndrome (PCO). The same patients were also treated with pulsatile hMG administration alone (Group II). Ovulation was observed in all twelve treatment cycles in Group I, and there were two pregnancies. In Group II, ovulation occurred in 22 of 26 treatment cycles. Ovarian hyperstimulation occurred in one cycle of Group I and in 5 of 26 cycles of Group II. The total dose per cycle of hMG to induce ovulation in Group I was significantly lower than that needed when only pulsatile hMG administration was used. In response to Buserelin administration, the concentrations of serum luteinizing hormone (LH) and follicle stimulating hormone (FSH) increased transiently and then declined to the normal range observed in the early follicular phase. The concentrations of FSH increased in response to hMG administration, resulting in a normal LH/FSH ratio. The present data demonstrated that pulsatile subcutaneous administration of hMG in addition to Buserelin was effective in inducing follicular maturation and ovulation in patients with PCO with a lower incidence of serious side-effects.

Topics: Adult; Buserelin; Clinical Trials as Topic; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Infusion Pumps; Menotropins; Ovulation Induction; Polycystic Ovary Syndrome

The use of exogenous gonadotropins for treatment of clomiphene-resistant chronic anovulation in women with the polycystic ovary syndrome (PCO) is hazardous and often ineffective, possibly because of the abnormal endogenous gonadotropin secretion characteristic of PCO. We evaluated the effect of leuprolide acetate, a long-acting GnRH agonist, on serum gonadotropin and sex steroid concentrations before and during human menopausal gonadotropin (hMG) induction of ovulation in women with PCO. In this controlled prospective randomized study, leuprolide was administered daily for 4 weeks, followed by concomitant hMG administration. Gonadotropin and steroid hormone concentrations were compared with those during ovulation induction cycles in women with PCO receiving hMG only. Daily administration of leuprolide for 4 weeks resulted in significantly decreased serum LH, estradiol, and testosterone concentrations, but no change in serum progesterone, FSH, and dehydroepiandrosterone sulfate. Compared to ovulation induction using hMG alone, leuprolide administration before and during hMG treatment prevented preovulatory rises in serum LH and P concentrations, while having no effect on serum FSH, testosterone, estradiol, and dehydroepiandrosterone sulfate. We conclude that leuprolide administered to women with PCO decreases gonadal steroid production and is capable of preventing premature luteinization during hMG induction of ovulation.

Topics: Adult; Anovulation; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Estradiol; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Luteinizing Hormone; Menotropins; Ovulation Induction; Polycystic Ovary Syndrome; Progesterone; Testosterone

The long-acting agonist analogue of LHRH, Buserelin (Hoechst) has been used to suppress endogenous gonadotrophins prior to induction of ovulation with low dose human menopausal gonadotrophin (HMG) in women with clomiphene-resistant polycystic ovary syndrome (PCOS). The results have been compared with those in a similar group of patients treated with HMG alone. Buserelin (900-1,500 micrograms/day) was given intranasally to 11 women who thereafter received a total of 33 cycles of treatment with low-dose HMG. The control group comprised 16 women who received 40 cycles of HMG without Buserelin pretreatment. The ovulation rate was similar in the two groups: Buserelin + HMG 70%, HMG alone 68% and both groups showed a high rate of single follicle ovulation (52 and 63%, respectively). The threshold dose of gonadotrophin required to induce a single follicle was similar in the two groups. Premature elevation of LH in the late follicular phase was common in women who received HMG alone, but did not occur in any cycle in the patients receiving Buserelin pretreatment. In summary, these data show that pretreatment with an LHRH analogue prevents a premature LH surge but it remains to be determined whether this will have a significant bearing on the rate of successful pregnancy in women with PCOS.

Topics: Anovulation; Buserelin; Clinical Trials as Topic; Drug Therapy, Combination; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Luteinizing Hormone; Menotropins; Ovulation; Polycystic Ovary Syndrome; Pregnancy

Topics: Buserelin; Chorionic Gonadotropin; Clinical Trials as Topic; Double-Blind Method; Estrogens; Female; Follicle Stimulating Hormone; Humans; Luteinizing Hormone; Menotropins; Ovulation Induction; Polycystic Ovary Syndrome

To evaluate the obstetric and perinatal outcomes of three routine endometrial preparation protocols in women with PCOS who underwent frozen embryo transfer (FET).. This was a retrospective study in women with PCOS who underwent FET in an academic reproductive medical center. A total of 2710 cycles were enrolled and classified into three groups according to different endometrial preparation protocols; human menopausal gonadotropin (HMG), letrozole + HMG, or hormone replacement therapy (HRT).. The stimulation groups had reduced risks of hypertensive disorders of pregnancy (HDP), large for gestational age (LGA) infants, and cesarean delivery than the HRT group. After adjustment for different confounder combinations in the two models, the frequencies of LGA and HDP in the letrozole + HMG group and the HMG group were still significantly lower than those in the HRT group. The letrozole + HMG group exhibited a reduced risk of LGA than HMG group after adjustment of confounders. A trend toward risk reductions in HDP and LGA was observe in turns of HRT, HMG, and letrozole + HMG groups, and the trends were statistically significant (P. In patients with PCOS, ovarian stimulation protocols for endometrial preparation are associated with reduced risks of HDP and LGA compared to HRT cycles. The use of letrozole could further reduce risk of LGA compared to HMG only protocol. We propose that ovarian stimulation protocols can be used widely for endometrial preparation in FET cycles in women with PCOS, especially with the use of letrozole.

Topics: Cryopreservation; Embryo Transfer; Female; Humans; Infant, Large for Gestational Age; Infant, Newborn; Letrozole; Menotropins; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy; Pregnancy Rate; Retrospective Studies

Hormone replacement therapy (HRT) regimen was suggested to be associated with a decreased rate of livebirth and a higher risk of hypertensive disorders of pregnancy (HDP) after frozen cleavage stage embryo transfer in women with polycystic ovary syndrome (PCOS). With the dramatically increased use of elective single embryo transfer, there is great need to explore the impacts of different endometrial preparation regimens on frozen single-blastocyst transfer in women with PCOS.. In this study, a total of 3941 women who diagnosed with PCOS and underwent single-blastocyst transfer during their first cycles of frozen embryo transfer (FET) between March 2012 and December 2020 were included. We retrospectively compared the pregnancy and neonatal outcomes after frozen single-blastocyst transfer with endometrial preparation by HRT regimen (n = 3540), ovulation induction by human menopausal gonadotropin (hMG) regimen (n = 226), and ovulation induction by letrozole regimen (n = 175).. After adjustment for confounders with multivariable logistic regression, the hMG regimen group [(58.4% vs. 49.6%; adjusted odds ratio (aOR): 1.43; 95% confidence interval (CI): 1.09-1.89)] and letrozole regimen group (58.9% vs. 49.6%; aOR: 1.42; 95% CI: 1.04-1.93) were associated with a higher rate of livebirth (primary outcome), compared with the group with HRT regimen. As to the secondary outcomes, the rate of pregnancy loss in the hMG regimen group (22.8% vs. 30.3%; aOR: 0.69; 95% CI: 0.48-1.00) and letrozole regimen group (16.9% vs. 30.3%; aOR: 0.48; 95% CI: 0.30-0.78) was also lower than that in the HRT regimen group. The pregnancy outcomes between the hMG regimen group and the letrozole regimen group were similar. We did not observe significant difference in the incidences of maternal and neonatal complications among these three groups.. Ovulation induction regimen with letrozole or hMG for endometrial preparation was associated with a higher livebirth rate and a lower pregnancy loss rate in frozen single-blastocyst transfer cycles among women with PCOS.

Topics: Abortion, Spontaneous; Embryo Transfer; Female; Humans; Infant, Newborn; Letrozole; Menotropins; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy; Retrospective Studies

Polycystic ovary syndrome (PCOS) is a main cause of anovulatory infertility in women of reproductive age. About 30% to 50% of patients with PCOS has high serum basal luteinizing hormone (LH) levels, and almost 5% of PCOS women with high LH have poor ovarian response (POR). We reported a case of a PCOS woman with high basal LH levels who canceled due to POR during two consecutive controlled ovarian stimulation treatments, which was considered to be related to the suppression of LH levels during downregulation. Clomiphene citrate (CC) combined with human menopausal urinary gonadotropin (HMG) mild regimen did not affect LH levels and obtained good follicular development, providing a new treatment insight for patients with PCOS combined with POR.. A 28-year-old PCOS woman with high basal LH levels, underwent IVF assisted pregnancy treatment in our hospital, whom canceled due to POR during two traditional controlled ovulation induction program. Follicular development was finally achieved with CC milder protocol.. This patient with the diagnosis of PCOS was undergone IVF assisted pregnancy treatment in our hospital.. CC protocol supports the development of follicular.. CC protocol resulted in better follicular development and high-quality embryos due to the continuous maintenance of an elevated LH levels.. PCOS women with poor ovarian response required relatively higher LH to maintain the normal development of follicles.

Topics: Adult; Clomiphene; Female; Fertility Agents, Female; Humans; Luteinizing Hormone; Menotropins; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy

MicroRNAs (miRNAs) are small RNA molecules that modulate post-transcriptional gene regulation. They are often used as promising non-invasive biomarkers for the early diagnosis of cancer. However, their roles in assisted reproduction are still unknown.. This prospective study was designed to evaluate the expression profiles of seven extracellular miRNAs (miR-7-5p, miR-202-5p, miR-378-3p, miR-224, miR-320a, miR-212-3p, and miR-21-5p) in human follicular fluid (FF) to explore the outcomes of in vitro fertilization (IVF). Of 255 women, 145 were without polycystic ovary syndrome (PCOS), and their ovarian assets were normal (NOR), while 110 were with normo-androgenic PCOS.. The combination of six FF miRNAs expression profile discriminated between PCOS and NOR women with a sensitivity of 79.2% and a specificity of 87.32% (AUC = 0.881 [0.61; 0.92], p = 0.001). MiR-202-5p significantly had a lower abundance level, and miR-378-3p had a high abundance level in pooled FF samples from patients treated with human menopausal gonadotropin (hMG) than those treated with recombinant follicle-stimulating hormone (rFSH) (p < 0.001). Our results showed that miRNA-320a was significantly different in top-quality embryos versus non-top-quality embryos on day 3 in NOR patients with a sensitivity of 80% and specificity of 71%, (AUC = [0.753 (0.651; 0.855)], p = 0.001). For clinical pregnancy outcome prediction, FF miRNA-21 exhibited high sensitivity (74.8%) and specificity (83.7%) with the AUC value of 0.774 (0.682; 0.865).. Conclusively, our results provide evidence that miR-7-5p, miR-378-3p, miR-224, miR-212-3p were a differentially high expression in normo-androgenic PCOS patients than NOR patients. While miRNA-320a was significantly different in top-quality embryos versus non-top-quality embryos on day 3 (p = 0.001). The expression level of FF miR-212-3p was significantly related to the probability of embryos to develop into a high-quality blastocyst in patients with normal ovarian reserve.

Topics: Adult; Blastula; Female; Fertilization in Vitro; Follicle Stimulating Hormone; Follicular Fluid; Gene Expression Regulation; Gene Ontology; Gene Regulatory Networks; Hormones; Humans; Menotropins; MicroRNAs; Ovarian Follicle; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Prospective Studies; Recombinant Proteins; Sensitivity and Specificity

There is currently a dispute over the choice of ovulation induction treatment for infertile women with polycystic ovary syndrome (PCOS). The objective of this study is to compare the therapeutic effect of pulsed rhythmic administration protocol (PRAP) with conventional letrozole + human menopausal gonadotropin (HMG) in patients with clomiphene-resistance polycystic ovary syndrome (PCOS). A retrospective analysis of 821 intrauterine insemination (IUI) cycles between January 2015 and January 2020 was performed. Of these, 483 cycles were treated with a pulsed rhythmic administration protocol (PRAP), and 338 cycles were treated with conventional letrozole + HMG protocol (LHP). The therapeutic effect of the two protocols has been compared. The pregnancy rate was 18.07% in the LHP and 27.07% in the PRAP. The ongoing pregnancy rate in LHP was 14.46% and in PRAP was 22.73%. The research suggests that PRAP is more effective than LHP and could be an adequate ovulation induction strategy for the IUI cycle of patients with clomiphene-resistance PCOS.

Topics: Adult; Aromatase Inhibitors; Clomiphene; Drug Administration Routes; Drug Resistance; Female; Fertility Agents, Female; Follow-Up Studies; Humans; Infertility, Female; Letrozole; Menotropins; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy; Pregnancy Rate; Retrospective Studies; Young Adult

The potential effects of high basal luteinizing hormone (LH) levels on human reproduction were controversial. To demonstrate the effects of elevated basal LH levels on the outcome of patients undergoing in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles, we performed a retrospective data analysis of 1011 polycystic ovarian syndrome (PCOS) patients treated with human menopausal gonadotropin and medroxyprogesterone acetate (hMG + MPA) protocol at our center between Nov. 2013 and Jun. 2017. PCOS patients with elevated basal LH levels had significantly higher LH exposure during the stimulation period. The group with LH ≥ 10 mIU/mL showed a lower mean total hMG dose used but higher numbers of oocytes retrieved, metaphase II oocytes, embryos and top-quality embryos developed than the groups with lower basal LH levels. Moreover, partial correlation analysis showed that the basal LH level was negatively correlated with the total hMG dose but positively correlated with the numbers of oocytes retrieved, metaphase II oocytes, embryos, and top-quality embryos. There were no significant differences in the rates of oocyte retrieval, fertilization, implantation, clinical pregnancy and miscarriage between the groups based on frozen embryo transfer (FET). We concluded that elevated basal LH level does not impair the final outcome of hMG + MPA-treated IVF/ICSI cycles in PCOS women.

Topics: Adult; Embryo Implantation; Embryo Transfer; Female; Fertilization in Vitro; Gonadotropins; Humans; Infertility, Female; Luteinizing Hormone; Medroxyprogesterone Acetate; Menotropins; Middle Aged; Oocyte Retrieval; Oocytes; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy; Retrospective Studies; Sperm Injections, Intracytoplasmic

To investigate the ability of anti-Mullerian hormone (AMH) to predict the step up of human menopausal gonadotropins (HMG) dose in women with polycystic ovarian syndrome (PCOS) undergoing IVF/ICSI cycles.. AMH was drawn before ovulation induction in 976 PCOS women scheduled for IVF/ICSI. After all cycles ended, a receiver operating characteristic (ROC) curve analysis was done to investigate the ability of AMH to predict step up of the HMG.. The area under the curve (AUC) was 0.820 95%CI (0.792-0.848), and a cutoff value of 4.6 ng/ml (sensitivity 74%, specificity 82%) for AMH was taken (p < 0.01). Cases were divided into two groups retrospectively; group (A) (AMH ≤4.6 ng/ml), and group (B) (AMH >4.6 ng/ml). No difference in the mean age (p = 0.147); BMI (p = 0.411), basal FSH (p = 0.221), and starting dose (p = 0.195); however, the dose at which the first response occurred was higher in group (B) (p < 0.01). The total dose and number of days were higher in group (B) (both p < 0.01) irrespective of the PCOS subtype or androgen levels. Severe OHSS was also higher in group (B) (p = 0.026).. PCOS with AMH >4.6 ng/ml are resistant to HMG stimulation, require dose step up during ART cycles, and are at higher risk for severe OHSS.

Topics: Adult; Anti-Mullerian Hormone; Female; Humans; Infertility, Female; Menotropins; Ovulation Induction; Polycystic Ovary Syndrome; Sperm Injections, Intracytoplasmic; Young Adult

The aim of this study was to explore the effect of clomiphene citrate (CC) on the cycle characteristics and outcomes of obese women with polycystic ovarian syndrome (PCOS) undergoing ovarian stimulation for in vitro fertilization (IVF).This is a retrospective cohort study, and it was conducted at the tertiary-care academic medical center.This study included 174 obese PCOS patients undergoing IVF.In the study group (n = 90), CC and human menopausal gonadotropin (HMG) were administered simultaneously beginning on cycle day 3, while in control group (n = 84) HMG was used only. Both of the 2 groups used medroxyprogesterone acetate (MPA) for preventing premature luteinizing hormone (LH) surges. Ovulation was cotriggered by a GnRH agonist and hCG when dominant follicles matured.The primary outcome measure was the number of oocytes retrieved. Secondary outcomes included the number of top-quality embryos, maturation rate, fertilization rate, cleavage rate, incidence of premature LH surge, and OHSS.The study group received obviously lower total HMG dose [1650 (975-4800) vs 2025 (1350-3300) IU, P = 2.038E-4] but similar HMG duration. While the antral follicle count (AFC) is higher in study group, the number of oocytes retrieved and top-quality embryos are remarkably less [5 (0-30) vs 13 (0-42), P = 6.333E-5; 2 (0-14) vs 3.5 (0-15), P = .003; respectively]. The mature oocyte rate is higher in study group (P = .036). No significant differences were detected in fertilization rate and cleavage rate between 2 groups.CC has a positive influence on cycle characteristics, but might be correlated with the impaired IVF outcomes (less oocytes retrieved and top quality embryos, lower oocyte retrieval rate) in obese PCOS patients undergoing IVF, when HMG and MPA are used simultaneously.

Topics: Academic Medical Centers; Adult; Clomiphene; Female; Fertility Agents, Female; Fertilization in Vitro; Humans; Infertility, Female; Medroxyprogesterone Acetate; Menotropins; Obesity; Oocytes; Ovulation Induction; Polycystic Ovary Syndrome; Retrospective Studies

Poor oocyte quality is a main concern for decreased reproductive outcomes in women with polycystic ovarian syndrome (PCOS) during controlled ovarian hyperstimulation (COH). A primary way to improve oocyte quality is to optimize the COH protocol. It was demonstrated that the viable embryo rate per oocyte retrieved in the Utrogestan and hMG protocol, a novel regimen based on frozen-thawed embryo transfer (FET), is statistically higher than that in the short protocol. Thus, a retrospective study was conducted to evaluate the endocrine characteristics and clinical outcomes in PCOS patients subjected to the Utrogestan and hMG protocol compared with those subjected to the short protocol.One hundred twenty three PCOS patients enrolled in the study group and were simultaneously administered Utrogestan and human menopausal gonadotropin (hMG) from cycle day 3 until the trigger day. When the dominant follicles matured, gonadotropin-releasing hormone agonist (GnRH-a) 0.1 mg was used as the trigger. A short protocol was applied in the control group including 77 PCOS women. Viable embryos were cryopreserved for later transfer in both groups. The primary outcome was the viable embryo rate per oocyte retrieved. The secondary outcomes included the number of oocytes retrieved, fertilization rate, and clinical pregnancy outcomes from FET cycles.The pituitary luteinizing hormone (LH) level was suppressed in most patients; however, the LH level in 13 women, whose basic LH level was more than 10 IU/L, surpassed 10 IU/L on menstruation cycle day (MC)9-11 and decreased subsequently. No significant between-group differences were observed in the number of oocytes retrieved (13.27 ± 7.46 vs 13.1 ± 7.98), number of viable embryos (5.57 ± 3.27 vs 5 ± 2.79), mature oocyte rate (90.14 ± 11.81% vs 93.02 ± 8.95%), and cleavage rate (97.69 ± 6.22% vs 95.89 ± 9.57%). The fertilization rate (76.11 ± 19.04% vs 69.34 ± 21.81%; P < 0.05), viable embryo rate per oocyte retrieved (39.85% vs 34.68%; P < 0.05), biochemical pregnancy rate (71.72% vs 56.67%; P < 0.05), clinical pregnancy rate (64.65% vs 51.65%; P < 0.05), and implantation rate (46.46% vs 31.35%; P < 0.05) in the study group were significant higher than those in the control group.This study shows that the Utrogestan and hMG protocol was feasible to improve the oocyte quality, possibly providing a new choice for PCOS patients undergoing IVF/ICSI treatments in combination with embryo cryopreservation.

Topics: Adult; Estrogen Replacement Therapy; Female; Fertility Agents, Female; Fertilization in Vitro; Humans; Infertility, Female; Luteinizing Hormone; Menotropins; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy; Progesterone; Retrospective Studies

Gonadotropin therapy and laparoscopic ovarian drilling (LOD) are treatment options for ovulation induction (OI) in clomiphene citrate (CC)-resistant polycystic ovary syndrome (PCOS) patients. The current evidence of the cost-effectiveness of both treatments is scarce, conflicting and performed from different health-economic perspectives.. A retrospective health-economic evaluation was performed from a societal perspective in which human menopausal gonadotropin (hMG) therapy (n = 43) was compared with LOD (n = 35), followed by OI with CC and/or hMG if spontaneous ovulation did not occur within 2 months. Data were collected until the patients were pregnant, with a time limit of 6 months after the onset of treatment. Outcomes were expressed as ongoing pregnancy rate and number of live-born children.. The ongoing pregnancy rate was 21/35 (60%) after LOD and 30/43 (69.8%) after hMG treatment (relative risk 0.85, 95% CI 0.61-1.19). The societal cost per patient, up to an ongoing pregnancy, was significantly higher after LOD versus hMG treatment (adjusted mean difference EUR 1,073, 95% CI 180-1,967).. This economic evaluation based on real-life data shows that the societal cost up to an ongoing pregnancy is less after hMG treatment when compared with LOD surgery in CC-resistant PCOS patients.

Topics: Adult; Anovulation; Clomiphene; Cost-Benefit Analysis; Female; Fertility Agents, Female; Humans; Infertility, Female; Laparoscopy; Menotropins; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy; Pregnancy Rate; Retrospective Studies; Treatment Failure; Young Adult

This study compares the cycle characteristics of clomiphene (CC) with CC+HMG (Human Menopausal Gonadotropin or Menotropins) in Polycystic Ovary Syndrome (PCOS) and non-PCOS infertile patients.. Patients were treated by CC + minimal HMg protocol. The cancellation rate, the mean number of different follicle sizes and endometrial thickness and pattern were compared.. The cancelled cycles due to non-responsiveness were significantly higher in CC compared to CC+ minimal HMg protocol. PCOS patients are significantly nonresponsive in CC cycle and hyperresponsive in CC+ minimal HMg cycles. The mean number of different sizes of follicles and the endometrial thickness were significantly higher in CC+ minimal HMg. PCOS patients were significantly different from non-PCOS regarding the number of mature follicle and endometrial thickness. The pregnancy rate was 11% (10.2% in non-PCOS and 12.2% in PCOS).. CC+ minimal HMg is a viable alternative to HMg /FSH only protocol in CC failure or resistant patients, and its efficacy can be mostly attributed to improvement of endometrial quality and increase in follicle number. Moreover, due to high cancellation of PCOS patients treated by this protocol, seemingly other alternatives should be found; perhaps sequential letrozole+HMg/FSH that have been shown to improve the ovarian response in this group of patients.

Topics: Adult; Case-Control Studies; Clomiphene; Drug Resistance; Endometrium; Female; Fertility Agents, Female; Humans; Infertility, Female; Menotropins; Ovarian Follicle; Polycystic Ovary Syndrome; Pregnancy; Pregnancy Rate; Prospective Studies; Treatment Failure; Treatment Outcome; Young Adult

Topics: Anovulation; Body Mass Index; Exercise; Feeding and Eating Disorders; Female; Gonadotropin-Releasing Hormone; Gonadotropins; Humans; Hypogonadism; Hypopituitarism; Hypothalamic Diseases; Infertility, Female; Menotropins; Ovulation Induction; Polycystic Ovary Syndrome; World Health Organization

Women with polycystic ovarian syndrome (PCOS) are known to have elevated circulating Anti-Müllerian hormone (AMH), which has been found to desensitize ovarian follicles to follicle stimulating hormone (FSH). The purpose of this study was to investigate the impact of high circulating AMH on ovarian responsiveness to ovulation induction with gonadotrophins in PCOS women.. This prospective observational pilot study was conducted in two collaborating Fertility Centres in the UK and Egypt. The study included 20 consecutive anovulatory women with PCOS who underwent 34 cycles of human menopausal gonadotrophin (hMG) ovarian stimulation using chronic low-dose step up protocol. Blood samples were collected for the measurement of serum AMH concentrations in the early follicular (day 2-3) phase in all cycles of hMG treatment. The serum levels of AMH were compared between cycles with good vs. poor response. The good response rates and the total dose and duration of hMG treatment were compared between cycles with high vs. low serum AMH concentrations.. Cycles with poor response (no or delayed ovulation requiring >20 days of hMG treatment) had significantly (p = .007) higher median{range} serum AMH concentration (6.5{3.2-13.4}ng/ml) compared to that (4.0{2.2-10.2}ng/ml) of cycles with good response (ovulation within 20 days of hMG treatment). ROC curve showed AMH to be a useful predictor of poor response to hMG stimulation (AUC, 0.772; P = 0.007). Using a cut-off level of 4.7 ng/ml, AMH had a sensitivity of 100% and specificity of 58% in predicting poor response. The good response rate was significantly (p < .001) greater in cycles with lower AMH (<4.7 ng/ml) compared to that in those with AMH > = 4.7 ng/ml (100% vs. 35%, respectively). All cycles with markedly raised serum AMH levels (> 10.2 ng/ml) were associated with poor response. Cycles with high AMH (> = 4.7 ng/ml) required significantly (p < .001) greater amounts (median {range}, 1087{450-1650}IU) and longer duration (20 {12-30}days) of hMG stimulation than cycles with lower AMH (525 {225-900}IU and 8{6-14}days).. PCOS women with markedly raised circulating AMH seem to be resistant to hMG ovulation induction and may require a higher starting dose.

Topics: Anti-Mullerian Hormone; Biomarkers; Female; Humans; Infertility, Female; Menotropins; Ovulation Induction; Pilot Projects; Polycystic Ovary Syndrome; Treatment Outcome

Topics: Cell Proliferation; Embryo Implantation; Endometrium; Estradiol; Female; Fertility Agents, Female; Fertilization in Vitro; Humans; Menotropins; Oocyte Retrieval; Polycystic Ovary Syndrome; Reproductive Techniques, Assisted; Treatment Outcome

To investigate the outcome of in vitro fertilization and embryo transfer (IVF-ET) in special infertile patients following modified super-long down-regulation protocol combined with human menopausal gonadotropin (HMG) stimulation.. Ninety-nine special patients (42 with endometriosis, 35 with PCOS, and 22 with insufficient down-regulation) who underwent modified super-long down-regulation protocol in 2008 were retrospectively analyzed. Gonadotropin releasing hormone analogues (GnRHa, 1.5 mg) was injected intramuscularly in mid-luteal phase twice and HMG was started 25 days later after the second GnRHa injection. Conventional IVF-ET was performed as routine procedure. The clinical outcomes were compared with those of 122 similar patients in the same period.. After modified super-long down-regulation, (1) in endometriosis patients, the average gonadotropin (Gn) used was (32.33 +/- 15.11) ampoules, duration of medication was (10.57 +/- 1.88) days, the progesterone (P) level on hCG day was (0.78 +/- 0.44) microg/L, and the clinical pregnancy rate (CPR) was 73.8%; (2) in PCOS patients, the average Gn used was (28.57 +/- 12.07) ampoules, the duration of medication was (11.71 +/- 2.07) days, the P level at hCG day was (0.65 +/- 0.39) microg/L, and the clinical pregnancy rate was 65.7%; (3) in insufficient down-regulation patients, the average Gn used was (26.22 +/- 12.07) ampoules, the duration of medication was (10.01 +/- 1.77) days, the P level at hCG day was (0.71 +/- 0.50) microg/L, and the clinical pregnancy rate was 72.7%. Compared with patients using regular down-regulation protocol, the clinical pregnancy rate was improved significantly and the cost decreased obviously. The clinical pregnancy rate significantly improved compared with that of routine long down-regulation groups.. Revised super-long protocol plus HMG is a cost-effective controlled ovary hyperstimulation (COH) regimen for infertile patients with endometriosis, PCOS and insufficient down-regulation.

Topics: Adult; Embryo Transfer; Endometriosis; Female; Fertility Agents, Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Humans; Infertility, Female; Menotropins; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy; Retrospective Studies; Treatment Outcome

Hormonal indices, phase pattern of estrous cycles, and histological structure of the ovaries were studied in female rats with polycystic ovaries caused by subcutaneous implantation of Silastic capsules with testosterone after consecutive treatment with non-steroid antiandrogen, flutamide (flutafarm), urinary FSH (menopur) and HCG (choragon). It was shown that while the plasma testosterone level was increased, administration of the drugs in subtherapeutical doses interrupted persistent diestrus, renewed estrous cycle, gonadal and uterine weights, induced appearance of postovulatory luteal bodies and restored fertility. Therefore, antiandrogen potentiation of pharmnnaco-dynamic effect of the gonadotropins with regard to their ability to ovulation induction was found out.

Topics: Androgen Antagonists; Androgen Receptor Antagonists; Animals; Anovulation; Chorionic Gonadotropin; Disease Models, Animal; Estrus; Female; Fertility Agents, Female; Flutamide; Menotropins; Ovulation; Polycystic Ovary Syndrome; Rats; Rats, Wistar; Receptors, Gonadotropin; Testosterone

To study effect of drug treatment in polycystic ovary syndrome patients with hyperprolactinemia.. We retrospectively studied 63 women with polycystic ovary syndrome and hyperprolactinemia from the Reproductive Medicine Center, Provincial Hospital between January 2005 and March 2007. According to the beginning time of bromocriptine, all women were divided into two groups. Group I was composed of 48 cases who received bromocriptine administration before induction of ovulation cycles, and the dose of bromocriptine was modulated depending on the level of serum prolactin. When serum prolactin was controlled at normal levels, we decreased the dosage of bromocriptine step by step (1.25 mg once), and then continued the treatment at maintenance dosage for no less than 3 weeks. After a baseline ultrasonographic examination on day 3, patients were treated with clomiphene citrate at a dosage of 100 mg (2 tablets/day) for 5 days of a normal cycle or progesterone-induced bleeding. On day 9, we monitored the growth conditions of follicles routinely with trans-vaginal ultrasound. If there was no dominant follicle, we added human menopausal hormone (hMG, 75 U/d) to the protocol. Human chorionic gonadotropin (hCG, 6000-10,000 IU) was given intramuscularly when the mean diameter of a follicle reached at least 18 mm. At the same time we instructed the patients to have sexual intercourses or carried out artificial inseminations before and after ovulation. Group II were 15 cases in which induction of ovulations were commenced almost simultaneously with beginning of bromocriptine. The same protocol was given to patients in group II. The procedures of ovulation induction and the outcomes of treatment were analyzed and compared.. Compared with group II , the days of using hMG in Group I was shorter by instructing the time of sexual intercourse. The difference was significant (P = 0.004). And there were similar results in the artificial insemination cycles (P = 0.009). The rate of pregnancy in group I (40%, 19/48) was higher than that in group II (27%, 4/15), but the difference was not obvious (P = 0.525 ).. Bromocriptine administration before the stimulated ovulation therapy can decrease the total dosage and treatment course of ovulating drugs. Induction of ovulations simultaneously with start of bromocriptine therapy can shorten the treatment time of infertility.

Topics: Adult; Bromocriptine; Chorionic Gonadotropin; Clomiphene; Drug Therapy, Combination; Female; Humans; Hyperprolactinemia; Infertility, Female; Menotropins; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy; Prolactin; Retrospective Studies; Treatment Outcome

This is a retrospective analysis of 89 patients who were undergoing controlled ovarian hyperstimulation for in vitro fertilization and embryo transfer in the Fertility Management Unit of the Department of Obstetrics, Gynaecology and Child Health, The University of the West Indies. Twenty-eight patients (Group A), who did not receive oral contraceptive pills prior to controlled ovarian hyperstimulation (COH) were compared with 61 patients in Group B treated with oral contraceptive pills for two months prior to undergoing COH assisted reproduction using the long protocol. The number of follicles, oocytes, estimated oestradiol levels on the day of administration of human chorionic gonadotrophin (hCG), pregnancy rates, miscarriage rates and the incidence of patients who developed ovarian hyperstimulation syndrome (OHSS) were the main outcome measures. The mean age and haematocrit were the same in each group. The number of follicles retrieved tended to be higher in Group A than in Group B (median 8 versus 6, p = 0.06) with significantly more oocytes being retrieved in Group A than Group B (p < 0.05). There were no statistically significant differences between the two groups in oestradiol levels, the proportion of patients with polycystic ovarian disease, the proportion of women who developed ovarian hyper-stimulation syndrome or pregnancy outcomes. There was no difference between the groups in measures of clinical severity of OHSS. In a logistic regression model the significant predictors of OHSS were haematocrit and oestradiol levels. There appeared to be no significant clinical benefit in administering oral contraceptive pills for two months to patients prior to COH.

Topics: Adult; Contraceptives, Oral, Hormonal; Embryo Transfer; Female; Fertility Agents, Female; Humans; Infertility, Female; Menotropins; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Polycystic Ovary Syndrome; Retrospective Studies; Treatment Outcome

We aimed to compare the effects of two different gonadotropins on steroid production in patients with polycystic ovary syndrome (PCOS). The study group comprised 20 infertile patients diagnosed with PCOS who were accepted into in vitro fertilization-embryo transfer and gamete intra-Fallopian transfer programs. Ten patients were consecutively allocated to a purified urinary follicle stimulating hormone (FSH) administration group while the other ten received human menopausal gonadotropin (hMG). All patients were pretreated with a gonadotropin releasing hormone-agonist. The patients were followed by daily vaginal ultrasonography until at least two follicles reached a diameter of 17 mm or an estradiol value of at least 100 pg/ml per follicle. To induce ovulation, human chorionic gonadotropin was given. On the 3rd day of menstruation, serum estradiol, luteinizing hormone (LH), FSH, total testosterone, androstenedione, dehydroepiandrosterone sulfate (DHEAS), insulin-like growth factor-I and insulin were measured. These same parameters were measured again on the day of follicle aspiration in both serum and follicular fluid. In both groups, the serum levels of estradiol and androstenedione were raised significantly, and on aspiration day the serum level of DHEAS was significantly raised in the FSH group but not in the hMG group. Our findings suggest that in PCOS patients exogenous hMG induces a different steroid synthesis pattern compared to pure FSH, hypothetically by reduction of the delta-5 steroid synthesis pathway in the adrenals and/or in the ovary.

Topics: Adult; Androstenedione; Chorionic Gonadotropin; Dehydroepiandrosterone Sulfate; Estradiol; Female; Fertilization in Vitro; Follicle Stimulating Hormone; Gamete Intrafallopian Transfer; Gonadotropin-Releasing Hormone; Humans; Infertility, Female; Insulin; Insulin-Like Growth Factor I; Menotropins; Ovulation Induction; Pilot Projects; Polycystic Ovary Syndrome

The goal of the treatment of infertility is to apply therapeutic techniques to patients in a safe manner and at the same time increase the chances for conceiving and delivering healthy babies: basic and clinical research is more and more finalized directed to these goals. The conference "Advances in Infertility Treatment" held in Fort Lauderdale, Florida on January 24-26, 2002 covered many clinical and research aspects of this important therapeutic area. Important discussed issues included the impact of age, lifestyle, and the genetic set-up of patients in the pathogenesis and development of infertility-causing disorders such as male reproductive dysfunction, polycystic ovary syndrome, and ovarian failure. New ovulation induction regimens that may optimize, reduce complications, and lower costs of ovarian stimulation procedures and of assisted reproduction in general were presented. This was the 5th Ferring Pharmaceuticals Conference in the area of reproductive medicine held in Florida.

Topics: Abortion, Spontaneous; Costs and Cost Analysis; Female; Florida; Humans; Infertility; Infertility, Female; Infertility, Male; Luteinizing Hormone; Male; Menotropins; Oocytes; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy; Preimplantation Diagnosis; Reproductive Techniques, Assisted; Sperm Injections, Intracytoplasmic

With the availability of laparoscopic ovarian cautery, there has been a resurgence in interest in the surgical treatment of clomiphene citrate-resistant polycystic ovary syndrome (PCOS). Comparison of ovulation and pregnancy rates has found no difference in success rates between ovarian cautery and gonadotropin ovulation induction for such women. We have therefore compared the cost of laparoscopic ovarian cautery with that of a typical cycle of gonadotropin ovulation induction, and also found that there is little difference. Because of the potential advantages of ovarian cautery, we recommend this surgery as the next line of treatment if clomiphene citrate fails to induce ovulation in PCOS patients, before gonadotropins are introduced.

Topics: Cautery; Chorionic Gonadotropin; Clomiphene; Cost-Benefit Analysis; Drug Costs; Drug Resistance; Female; Follicle Stimulating Hormone; Gonadotropins; Humans; Laparoscopy; Menotropins; Ovulation; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy; Recombinant Proteins

To study the benefits of a low-dose stimulation (LDS) protocol with purified urinary follicle-stimulating hormone in patients with polycystic ovaries who have presented previously with a very high ovarian response to a standard hMG stimulation.. Cohort study.. Fertility center in a university hospital.. Sixty-one patients involved in an IVF/ICSI program from January 1995 to December 1996.. The patients were first stimulated with a standard protocol using hMG and presented with a very high ovarian response. These patients were then stimulated a second time using a low-dose protocol. Cryopreserved embryos were transferred in later artificial or natural cycles until to December 1999.. Number of gonadotropin ampules; estradiol level on the day of ovulation induction; follicles, oocytes, and cryopreserved zygotes; fertilization, implantation, and pregnancy rates; and number of ovarian hyperstimulation syndromes (OHSS).. The number of ampules used, the estradiol level reached, and the number of oocytes obtained were significantly lower under the LDS than the standard protocol. High implantation (21.8%) and clinical pregnancy (38.4%) rates were obtained after LDS. The cumulated deliveries per cycle started and per patient were, respectively, 41.6% and 52.5%. Five patients suffered OHSS with the standard protocol, and none with the LDS.. The LDS protocol offers a safe and efficient treatment for patients who present with echographic polycystic ovaries and are at risk of an excessive ovarian response to standard IVF stimulation protocols.

Topics: Adult; Cohort Studies; Delivery, Obstetric; Dose-Response Relationship, Drug; Embryo Implantation; Estradiol; Female; Fertilization in Vitro; Follicle Stimulating Hormone; Humans; Menotropins; Oocytes; Ovarian Hyperstimulation Syndrome; Ovary; Polycystic Ovary Syndrome; Pregnancy; Pregnancy Rate; Risk Factors; Specimen Handling; Sperm Injections, Intracytoplasmic

To examine the stage-specific follicular response to recombinant human FSH (rhFSH), urinary FSH (uFSH), and hMG preparations.. In vitro follicle culture.. Small preantral and tertiary follicles isolated from adult normal BDF-1 mice and androgen-sterilized mice were cultured with rhFSH, uFSH, and hMG for 4 days.. Follicular diameter. Immunoreactive inhibin, E2, and progesterone concentrations in cultured medium.. The minimal effective dose of rhFSH, uFSH, and hMG for the follicular growth of small preantral follicles from normal mice was 10 mIU/mL, 1 mIU/mL, and 0.1 mIU/mL, respectively. For tertiary follicles from normal mice, the minimal effective dose of rhFSH, uFSH, and hMG was 10 mIU/mL, 10 mIU/mL, and 1 mIU/mL, respectively. The minimal effective dose of hMG for the follicular growth of small preantral follicles from androgen-sterilized mice was 0.01 mIU/mL, and that of rhFSH and uFSH on tertiary follicles from androgen-sterilized mice was 1 mIU/mL and 10 mIU/mL, respectively. No significant increase was found in the follicular diameter of the tertiary follicles from androgen-sterilized mice as a result of stimulation by hMG, but an hMG dose of >10 mIU/mL produced a significant increase in progesterone secretion.. Human menopausal gonadotropin preparation acts detrimentally on follicles from androgen-sterilized mice by increasing the sensitivity of small preantral follicles to FSH and by inducing the luteinization of tertiary follicles.

Topics: Age Factors; Androgens; Animals; Anovulation; Cells, Cultured; Estradiol; Female; Follicle Stimulating Hormone; Humans; Inhibins; Menotropins; Mice; Mice, Inbred Strains; Ovarian Follicle; Polycystic Ovary Syndrome; Progesterone; Recombinant Proteins

To assess serum leptin levels based on body habitus and ovarian morphology during controlled ovarian hyperstimulation.. Prospective analysis.. University IVF program.. Women undergoing IVF-ET were divided into two groups, obese ovulatory women (n = 6; mean (+/-SD) body mass index, 30.1 +/- 0.6 kg/m(2)) and lean ovulatory women (n = 20); mean (+/- SD) body mass index 22.0 +/- 0.2 kg/m(2)). Lean women were categorized further according to whether they had polycystic-appearing ovaries (n = 8) or normal-appearing ovaries (n = 12).. Controlled ovarian hyperstimulation and IVF.. Serum estradiol, testosterone, and leptin.. Mean (+/- SD) leptin levels were significantly higher before and after GnRH agonist down-regulation in obese women (41.7 +/- 5.2 pg/mL and 36.1 +/- 5.8 pg/mL, respectively) compared with lean women (8.4 +/- 1.0 pg/mL and 6.9 +/- 1.1 pg/mL, respectively). Mean (+/- SD) leptin levels increased significantly in both groups (54.5 +/- 5.1 pg/mL and 11.7 +/- 1.2 pg/mL, respectively), and the mean (+/-SD) percentage increase was similar (55% +/- 18% and 54.8% +/- 17%, respectively). Mean (+/-SD) leptin levels were similar in women with polycystic-appearing and normal-appearing ovaries before controlled ovarian hyperstimulation, but increased significantly in women with polycystic-appearing ovaries afterward (14.7 +/- 1.8 pg/mL and 9.3 +/- 1.0 pg/mL, respectively).. Significant increases in leptin levels occur during controlled ovarian hyperstimulation, suggesting that leptin plays a role in follicular growth and maturation. The exaggerated response in women with polycystic-appearing ovaries reflects either a greater number of recruited follicles or a predisposition of adipocytes to leptin production.

Topics: Adult; Body Weight; Case-Control Studies; Estradiol; Female; Gonadotropin-Releasing Hormone; Humans; Infertility, Female; Leptin; Menotropins; Obesity; Ovary; Ovulation Induction; Polycystic Ovary Syndrome; Prospective Studies; Testosterone

Topics: Clinical Trials as Topic; Female; Fertilization in Vitro; Follicle Stimulating Hormone; Humans; Menotropins; Meta-Analysis as Topic; Polycystic Ovary Syndrome; Pregnancy; Pregnancy Rate

To investigate the risk factors for failure of ovulation induction in polycystic ovary syndrome (PCOS) patients and establish congression and regression tree (CART) model.. Sex hormones were measured in 103 PCOS patients and 31 healthy women by radioimmunoassay, oral glucose tolerance test (OGTT) and insulin release test were done as well. Three ovulation induction protocols including clomiphene (CC)/chorionic gonadotrophin (hCG), CC/menotrophins (hMG)/hCG and gonadotrophin releasing hormone agonist(GnRH-a)/hMG/hCG were used for PCOS related infertility. Transvaginal ultrasonography was used for monitoring. The correlation between hormone levels and clinical outcomes was analyzed by CART method.. The ovulation rate in patients with 2-hour blood insulin level < or = 68.9 mIU/L during OGTT was 86.9%, which was significantly higher than those with > 68.9 mIU/L (61.9%, P < 0.05). In the model, the insulin and glucose level of 0 min, 60 min during OGTT acted obviously, but estradiol and basal T level did not, the protocol of ovulation induction was not able to enter the model.. Two hour insulin level during OGTT is the most important factor affecting the outcome of ovulation induction, while the others parameters of glucose and insulin level have useful action too.

Topics: Adult; Chorionic Gonadotropin; Clomiphene; Decision Trees; Drug Therapy, Combination; Female; Fertility Agents, Female; Gonadotropin-Releasing Hormone; Humans; Insulin; Menotropins; Ovulation Induction; Polycystic Ovary Syndrome; Treatment Outcome

Topics: Adult; Anticoagulants; Female; Fluid Therapy; Humans; Infertility, Female; Menotropins; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Polycystic Ovary Syndrome; Risk Factors; Ultrasonography; Venous Thrombosis

To investigate follicular effects of recombinant human follicle stimulating hormone (rhFSH) induction on women with polycystic ovary syndrome (PCOS), steroid content was compared in mature follicles obtained using a long luteinizing hormone-releasing hormone agonist plus rhFSH or human menopausal gonadotrophin (HMG) in PCOS women and controls participating in an in-vitro fertilization programme. Follicular fluids (144 samples) were collected at oocyte retrieval by individual selective aspiration. Oocyte maturity and fecundability were assessed. Plasma and intrafollicular 17beta-oestradiol, progesterone, testosterone concentrations were assayed individually. No significant difference was seen in oocyte maturity and fecundability between PCOS and controls following rhFSH, or between PCOS rhFSH and HMG group. 17beta-oestradiol, testosterone and progesterone concentrations were lower in PCOS follicular fluid following rhFSH than HMG but the difference was not significant. Progesterone concentration, 17beta-oestradiol/progesterone, 17beta-oestradiol/testosterone were significantly different between the two induction groups, for PCOS fertilized oocyte follicles (P = 0.01, P < 0.05 and P < 0.05 respectively). Steroidogenic enzymatic activity seems to be regulated in healthy follicular cells in PCOS as well as in normal patients upon ovarian induction. Following rhFSH, higher PCOS follicular progesterone concentrations leading to a theoretically increased fecundability could suggest that recombinant FSH is a better inducer which needs to be confirmed.

Topics: Adult; Estradiol; Female; Fertilization in Vitro; Follicle Stimulating Hormone; Follicular Fluid; Humans; Infertility, Female; Male; Menotropins; Oocytes; Ovarian Follicle; Ovulation Induction; Polycystic Ovary Syndrome; Progesterone; Recombinant Proteins; Testosterone

To investigate serum and follicular fluid (FF) insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding protein-3 (IGFBP-3) behavior in superstimulated cycles in patients with polycystic ovary syndrome (PCOS).. Controlled clinical study.. Department of Obstetrics and Gynecology, University of Naples.. Thirty-two patients with regular menses and tubal and/or male factor infertility and 21 patients with PCOS undergoing IVF.. The IVF program used leuprolide acetate suppression followed by sequential hMG in the subsequent cycle. After follicular development, hCG administration was followed 34-36 hours later by oocyte retrieval.. E2, GH, IGF-I, and IGFBP-3 assayed by RIA and immunoradiometric assay.. The controls and patients with PCOS showed similar increases in E2 and GH titers in response to FSH stimulation. Serum IGF-I did not change in either group and was equivalent in the FF. Patients with PCOS had a higher FF IGFBP-3 titer and did not show the decrease in serum IGFBP-3 levels of the control group after FSH stimulation.. The apparent failure of IGFBP-3 reduction in patients with PCOS alters IGF-I bioavailability. Increased sequestration of IGF-I affects ovarian steroidogenesis and may explain the poor response to gonadotropin stimulation.

Topics: Adult; Chorionic Gonadotropin; Estradiol; Female; Follicle Stimulating Hormone; Human Growth Hormone; Humans; Infertility, Female; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Leuprolide; Male; Menotropins; Polycystic Ovary Syndrome

To avoid a high cancellation rate and/or a high multiple pregnancy rate due to multifollicular development in gonadotrophin stimulated cycles, such cycles were converted in the same cycle to in vitro fertilization/embryo transfer (IVF/ET). The results from a four year period using this strategy are summarized.. Seventy-three anovulatory women (seven WHO group I, 66 WHO group II) were studied during this period. In a majority of the cycles a GnRH-analogue was used for down-regulation according to a long protocol, followed by stimulation with FSH and/or hMG.. Out of 154 WHO group II gonadotrophin stimulation cycles intended for ovulation induction, 25 cycles were converted to IVF. The pregnancy and delivery rates in the IVF-converted cycles were 50% and 41%, respectively, and 31% and 22% when gonadotrophin stimulation was followed by intercourse. The cancellation rate, including both ovulation induction and IVF cycles, was 15% and the multiple pregnancy rate was 30%, mainly twins. Lean women achieved better outcome than obese women. In WHO group I only 12 cycles were performed. One cycle was converted to IVF resulting in delivery and one cycle was cancelled. The pregnancy- and delivery rates were both 50% when gonadotrophin stimulation was followed by intercourse.. It is concluded that the option to convert a gonadotrophin stimulation cycle to IVF in the same cycle, in cases of multifollicular development, seemed to be a good alternative. The conversion results in a low cancellation rate and a low incidence of high order multiple pregnancies. Patients should be informed of this opportunity before entering ovulation stimulation.

Topics: Adult; Anovulation; Female; Fertilization in Vitro; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Menotropins; Ovarian Follicle; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy; Pregnancy, Multiple

To determine the efficiency and comparison of two different protocols, human menopausal gonadotropin (hMG) plus gonadotropin-releasing hormone analog (GnRH-a) and low-dose hMG to reduce multifollicular development in clomiphene-resistant polycystic ovary syndrome (PCOS) patients.. Prospective comparative and pilot study in 20 patients for 31 cycles. The first group (n = 10) was treated with buserelin acetate, 600 micrograms/d, for six weeks before ovulation induction with hMG in conventional doses for 14 cycles. The other group (n = 10) was treated only with low-dose hMG for 17 cycles. All cycles were compared in terms of the number of follicles per cycle, cycles human chorionic gonadotropin withheld, estradiol level on ovulation day, treatment duration and number of ampules used per cycle. In addition, the outcome of cycles and complications of multifollicular development, ovarian hyperstimulation syndrome (OHSS) and multiple pregnancy were determined.. As compared with the GnRH-a + hMG protocol, the low-dose hMG protocol yielded less multifollicular (57.1% vs. 17.6%) and more monofollicular (35.7% vs. 70.6%) development. Consequently, less OHSS (21.4% vs. 0%) and multiple pregnancy (10% vs. 0%) occurred in the low-dose group.. Low-dose hMG therapy has distinct advantages in eliminating multifollicular development and related complications in clomiphene citrate-resistant PCOS patients. The addition of GnRH-a to gonadotropins does not change the incidence of multifollicular development.

Topics: Adult; Anovulation; Clomiphene; Dose-Response Relationship, Drug; Drug Resistance; Female; Fertility Agents, Female; Gonadotropin-Releasing Hormone; Humans; Infertility; Menotropins; Ovarian Follicle; Ovulation Induction; Pilot Projects; Polycystic Ovary Syndrome; Prospective Studies

To examine the association between the midfollicular FSH-LH ratio and the number of follicles, and the multifollicular ovarian response to gonadotropin stimulation in patients with polycystic ovary syndrome (PCOS) with normal basal LH and FSH levels.. Eighteen patients who had an abandoned treatment cycle because of multifollicular ovarian response. For comparison, all other completed treatment cycles in the same group of patients were used.. The dose of hMG or FSH, daily effective dose, day 8 serum FSH and LH concentration, day 8 number of follicles > or = 8 mm, E2 and number of follicles on hCG day or day of cycle was abandoned.. In the abandoned cycles, day 8 serum LH concentrations were significantly lower and day 8 number of follicles and FSH-LH ratios were significantly higher compared with the completed cycles. A high predictive power (> 90%) for multifollicular response was established by using a set of two criteria: a FSH-LH ratio > or = 1.6 and the number follicles > or = 7 as the cutoff point.. When aiming for a monofollicular response in women with PCOS and normal basal FSH and LH levels, cycles with high midfollicular FSH-LH ratios (> or = 1.6) and a high number of follicles (> or = 7) are those prone to develop a multifollicular ovarian response.

Topics: Adult; Biomarkers; Chorionic Gonadotropin; Estradiol; Female; Follicle Stimulating Hormone; Humans; Luteinizing Hormone; Menotropins; Menstrual Cycle; Ovarian Follicle; Ovulation Induction; Polycystic Ovary Syndrome; Predictive Value of Tests; Reference Values; Retrospective Studies

To determine Müllerian inhibiting substance (MIS) levels in follicular fluid (FF) and sera of IVF patients.. Prospective study.. Fertility center.. Sixty-six patients: 20 with tubal factor infertility, 17 with polycystic ovary syndrome (PCOS), and 29 with endometriosis.. All patients underwent ovarian stimulation with hMG and/or FSH, as well as oocyte retrieval for IVF.. Follicular fluid and serum MIS levels and oocyte fertilization rates.. Levels of MIS in FF and sera of PCOS patients were significantly higher than those in tubal factor patients: 7.01 +/- 1.52 versus 1.65 +/- 0.23 ng/mL (mean +/- SE) and 2.97 +/- 0.52 versus 0.92 +/- 0.19 ng/mL, respectively. In endometriosis patients, follicular fluid and serum MIS levels were not significantly different from those in tubal factor patients. In PCOS patients, the percentage of immature oocytes retrieved (17.9% +/- 5.0%) was significantly higher compared with tubal factor (1.5% +/- 1.0%) and endometriosis (9.2% +/- 2.3%) patients. The percentage of oocytes fertilize was significantly lower in PCOS patients (30.2% +/- 5.3%) compared with tubal factor (62.2% +/- 5.5%) and endometriosis (37.5% +/- 5.7%) patients.. Women with PCOS had higher serum and follicular fluid MIS levels, a higher percentage of immature oocytes, and lower fertilization rates than women with endometriosis or pelvic adhesions.

Topics: Adult; Anti-Mullerian Hormone; Endometriosis; Fallopian Tube Diseases; Female; Fertilization in Vitro; Follicle Stimulating Hormone; Follicular Fluid; Glycoproteins; Growth Inhibitors; Humans; Infertility, Female; Menotropins; Ovulation Induction; Polycystic Ovary Syndrome; Prospective Studies; Testicular Hormones

To determine the efficacy of IV albumin in the prevention of severe ovarian hyperstimulation syndrome (OHSS).. Prospective study group with historical control.. University hospital-based IVF program.. Between 1993 and 1995, 42 consecutive patients undergoing IVF-ET or tubal ET who had serum E2 levels > or = 3,600 pg/mL (conversion factor to SI unit, 3.671) on the day of hCG administration and/or > or = 20 oocytes retrieved were considered at high risk for severe OHSS and were selected as the control group. From December 1995 to October 1996, IV albumin was given to 30 consecutive patients who fulfilled these criteria.. The treatment group received IV albumin after oocyte retrieval.. Occurrence of severe OHSS.. None of the 16 patients in the treatment group in nonconception cycles developed severe OHSS, compared with 5 (21.7%) of 23 in the control group. In conception cycles, 4 (28.6%) of 14 patients in the treatment group developed severe OHSS, compared with 9 (47.4%) of 19 in the control group. All 4 patients with multiple pregnancies in the treatment group developed severe OHSS, compared with 3 (60%) of 5 in the control group. None of the 10 patients with singleton pregnancies in the treatment group developed severe OHSS, compared with 6 (42.9%) of 14 in the control group.. Intravenous albumin prevents severe OHSS in high-risk patients who did not conceive or who carried singleton pregnancies, but not in the patients with high-order pregnancies.

Topics: Adult; Albumins; Chorionic Gonadotropin; Embryo Transfer; Estradiol; Female; Fertilization in Vitro; Humans; Menotropins; Ovarian Hyperstimulation Syndrome; Polycystic Ovary Syndrome; Pregnancy; Pregnancy, Multiple; Prospective Studies; Risk Factors

To evaluate the complications and outcome of pregnancy in women with polycystic ovary disease (PCOD).. The course and outcome of 47 singleton pregnancies in women with well-documented PCOD were compared with those in 100 healthy controls.. Women with PCOD had a significantly higher body mass index as compared to the control group (P < .05); however, the proportion of lean versus obese subjects in the two groups was similar. The incidence of an abnormal glucose challenge test, gestational diabetes mellitus and pregnancy-induced hypertension was significantly increased in pregnant women with PCOD (P < .05). When lean PCOD subjects were compared with lean control subjects, the difference in the incidence of the above complications was still significant (P < .05). The incidence of pregnancy complications was similar when obese PCOD subjects were compared with obese controls.. Women with PCOD were at increased risk of gestational diabetes and pregnancy-induced hypertension, and this risk appeared to be independent of body mass index.

Topics: Adult; Body Mass Index; Clomiphene; Dexamethasone; Diabetes, Gestational; Embryo Transfer; Female; Fertilization in Vitro; Glucose Tolerance Test; Humans; Hypertension; Infertility, Female; Menotropins; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy; Pregnancy Complications; Pregnancy Outcome

Using a retrospective analysis, we compared cumulative pregnancy rates, early pregnancy failure rates and multiple pregnancy rates in couples with polycystic ovarian syndrome (PCOS) (n = 148), hypogonadotrophic or eugonadotrophic hypogonadism (n = 91) and unexplained infertility (n = 117), who were treated in an ovulation induction clinic between January 1991 and December 1995. The women were treated with either human menopausal gonadotrophin (HMG) or purified follicle stimulating hormone (FSH). The cumulative pregnancy rate (derived from life-table analysis) after four ovulatory treatment cycles was 70% in the PCOS group, 74% in the hypogonadism group and 38% in the unexplained infertility group. The cumulative pregnancy rate in the unexplained infertility group was significantly lower than the other groups (P < 0.001) but there was no significant difference between PCOS and hypogonadism using the log rank test. The early pregnancy failure rate was 25% in the PCOS group, 27% in the hypogonadism group and 26% in the unexplained infertility group (chi(2) = 0.132, not significant). The multiple pregnancy rate was 20% in the PCOS group, 30% in the hypogonadism group and 17% in the unexplained infertility group (chi(2) = 2.105, not significant). Treatment of anovulatory infertility using HMG or FSH is effective irrespective of the cause. Couples with unexplained infertility are less successfully treated using HMG: correction of unexplained infertility may involve more than simple correction of possible subtle ovulatory defects.

Topics: Adult; Body Mass Index; Female; Fetal Death; Follicle Stimulating Hormone; Humans; Hypogonadism; Infertility, Female; Male; Menotropins; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy; Pregnancy Outcome; Pregnancy, Multiple; Retrospective Studies

In order to determine which factors influence the large variations in sensitivity to gonadotrophins witnessed in women with polycystic ovary syndrome (PCOS), a prospective study was conducted of the correlation between basal clinical and endocrinological features and gonadotrophin requirements of 20 women with clomiphene-resistant PCOS undergoing ovulation induction. Baseline evaluation of serum concentrations of luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone, fasting insulin, insulin-like growth factor-1 (IGF-1), IGF binding protein-1 (IGFBP-1) and sex hormone-binding globulin (SHBG) were performed before administering gonadotrophin-releasing hormone agonist (GnRHa). Two weeks later, human menopausal gonadotrophin (HMG) was given in a standard individualized protocol according to ovarian response, until human chorionic gonadotrophin (HCG) was given. Serum concentrations of insulin, IGF-1, and IGFBP-1 were unaffected by GnRHa. The BMI correlated positively with insulin and inversely with IGFBP-1 serum concentrations and insulin and IGFBP-1 were inversely correlated. The amount of HMG required correlated positively with BMI and insulin concentrations and inversely with IGFBP-1 in the whole group and these correlations were maintained in the sub-group of lean women. No correlation was observed between HMG requirements and IGF-1 or other hormones. Women with hyperinsulinaemia and low IGFBP-1 concentrations required significantly more HMG. Multiple regression analysis revealed that insulin concentration is the most significant determinant of HMG requirement even when dissociated from BMI. We concluded that requirements of HMG in PCOS is not merely determined by obesity but by a cardinal role of insulin concentrations which, when high, induce, hypothetically, a hyperandrogenic intrafollicular milieu.

Topics: Adult; Female; Fertility Agents, Female; Humans; Insulin; Insulin-Like Growth Factor Binding Protein 1; Insulin-Like Growth Factor I; Menotropins; Ovulation Induction; Polycystic Ovary Syndrome; Prospective Studies

Hyperreactio luteinalis is a non-neoplastic tumor-like ovarian lesion associated with pregnancy. Most patients are asymptomatic, with the ovarian enlargement being incidentally discovered at the time of cesarean section. It can simulate a neoplasm on clinical, gross and sometimes microscopic examination. We report a case of hyperreactio luteinalis in a patient, who was diagnosed as having polycystic ovary disease before conceiving a triplet pregnancy after three treatment cycles of human menopausal gonadotropin-human chorionic gonadotropin therapy, and discuss its pathogenesis.

Topics: Adult; Chorionic Gonadotropin; Diagnosis, Differential; Drug Therapy, Combination; Female; Fertility Agents, Female; Humans; Menotropins; Ovarian Cysts; Ovarian Neoplasms; Polycystic Ovary Syndrome; Pregnancy; Pregnancy Complications; Pregnancy, Multiple; Triplets

Severe ovarian hyperstimulation syndrome (OHSS) leads to changes in laboratory analyte concentrations. Whereas elevated aminotransferase activity is often observed, a cholestatic course with hyperbilirubinaemia and icterus seldom occurs. In this report, the case of a 33 year old patient with polycystic ovary syndrome (PCOS) is described who, after stimulation with human menopausal gonadotrophin (HMG), developed severe OHSS with haemoconcentration, ascites, hydrothorax, elevated aminotransferases, hyperbilirubinaemia and icterus. The patient did not become pregnant and the OHSS regressed, together with the normalization of laboratory and clinical parameters and disappearance of the icterus. During the course of an OHSS cholestasis with icterus may occur, which could be explained by a reactive cholestatic hepatosis as a reaction to the hormonal changes induced by the stimulation therapy.

Topics: Adult; Chorionic Gonadotropin; Estradiol; Female; Humans; Hyperbilirubinemia; Infertility, Female; Jaundice; Menotropins; Ovarian Follicle; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Polycystic Ovary Syndrome

A retrospective study of a series of pregnant patients with polycystic ovarian syndrome following in vitro fertilization-embryo transfer was conducted to assess the outcome after ovarian stimulation by different protocols. Forty-one pregnancies were evaluated in patients with polycystic ovarian syndrome who conceived during in vitro fertilization-embryo transfer using human menopausal gonadotropin alone (17 pregnancies), or combined with gonadotropin releasing hormone analog (24 pregnancies). The demographic data of in vitro fertilization-embryo transfer cycles and pregnancy outcome were compared with the use of Student's t-test, the Mann-Whitney U test and Fisher's exact test, where appropriate. Among the pregnancies that were initiated following treatment, the protocol of the combination of the two was not associated with a higher rate of deliveries. The rate of first-trimester abortions was not statistically different between the two groups. These results suggest that the combined use of gonadotropin releasing hormone agonist and human menopausal gonadotropin in an in vitro fertilization program may not have beneficial effects on pregnancy outcome in patients with polycystic ovarian syndrome.

Topics: Adult; Drug Combinations; Embryo Transfer; Estradiol; Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Humans; Luteinizing Hormone; Menotropins; Ovary; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy; Pregnancy Outcome; Progesterone; Retrospective Studies; Statistics as Topic; Triptorelin Pamoate

To examine the influence of polycystic ovarian disease (PCOD) on the levels of total renin in plasma and follicular fluid (FF) after stimulation with hMG.. Comparative study of the plasma and FF concentrations of total renin in women with and without PCOD after stimulation with hMG.. In vitro fertilization-embryo transfer program at the Department of Obstetrics and Gynecology, the University Central Hospital of Turku, Finland.. Thirty-six women undergoing IVF-ET for infertility with (n = 10) or without (n = 26) ultrasonographically diagnosed PCOD. Of the latter group, 15 women had tubal infertility, and the rest suffered from an anovulatory infertility and reacted with PCO-like ovarian response to stimulation.. The concentrations of total renin in plasma and FF, serum E2, and protein in FF.. The concentrations of plasma total renin after the gonadotropin stimulation were significantly higher in the PCOD and PCO-like groups when compared with the tubal group. The concentration of total renin in FF and the ratio of total renin per protein in FF were higher in the PCOD and PCO-like groups than in the tubal group, but the differences did not reach statistical significance. Positive correlations were found between the plasma total renin and serum E2 concentrations in the PCO-like and in the tubal group and between plasma total renin concentrations and the number of mature follicles in all groups. Follicular fluid total renin did not correlate with FF protein in any group. All findings were independent of the total hMG dosage used and the body mass index of the patients.. In the present study the concentrations of total renin in plasma were enhanced markedly after gonadotropin stimulation in women with PCOD compared with women having tubal infertility. The pattern of the hormonal secretions revealed a group of infertile patients reacting biochemically like women with PCOD.

Topics: Adult; Embryo Transfer; Estradiol; Fallopian Tube Diseases; Female; Fertilization in Vitro; Follicular Fluid; Humans; Infertility, Female; Menotropins; Ovulation Induction; Polycystic Ovary Syndrome; Renin; Ultrasonography

One of the main endocrinological disturbances in patients with polycystic ovarian syndrome (PCOS) is the increased baseline concentrations of luteinizing hormone (LH) and consequently a high LH:follicle-stimulating hormone (FSH) ratio. The aim of this study was to assess the relationship between the baseline LH:FSH ratio with the stimulation response and the miscarriage risk in PCOS women stimulated for assisted reproduction techniques (ART) with and without gonadotrophin-releasing hormone analogue (GnRHa). Two groups of PCOS patients were analysed retrospectively. Group A (n = 20, 20 cycles) consisted of women stimulated with human menopausal gonadotrophin (HMG), and group B (n = 128, 162 cycles) comprised women stimulated with buserelin-long/HMG. LH and FSH concentrations were measured during the early follicular phase (days 4-6) in a preceding spontaneous or progestin-induced cycle. The following parameters were assessed: number of follicles developed, number of oocytes obtained and percentage of mature oocytes, as well as number of abortions and live births. In group A, the baseline LH:FSH ratio was correlated inversely with the number of follicles developed (P < 0.05), the number of oocytes obtained (P < 0.05) and the percentage of mature oocytes (P < 0.05). In group B, no correlation was found between the LH:FSH ratio and the number of follicles and oocytes, because their numbers were relatively constant irrespective of the baseline LH:FSH ratio, but a significant inverse correlation was noted with the percentage of mature oocytes (P < 0.001). However, a comparison of the slopes of the curve indicated a better correlation between the LH:FSH ratio and the percentage of mature oocytes in group A than in group B (P < 0.05). These findings were also confirmed when patients were subdivided according to the LH:FSH ratio (< 3 or > or = 3). Furthermore, in women who miscarried, the mean LH:FSH ratio was significantly higher than in women having a live birth. In conclusion, in PCOS patients stimulated with HMG, a high basal LH:FSH ratio appears to have an adverse effect on the number of follicles and oocytes, as well as on oocyte maturity. On the other hand, the administration of GnRHa in the long protocol seems to reverse this detrimental effect on follicle and oocyte development. Furthermore, a higher LH:FSH ratio seems to predict a greater possibility for miscarriage, despite the use of GnRHa.

Topics: Abortion, Spontaneous; Buserelin; Female; Follicle Stimulating Hormone; Follicular Phase; Humans; Infertility, Female; Luteinizing Hormone; Menotropins; Ovarian Follicle; Polycystic Ovary Syndrome; Pregnancy; Prognosis; Reproductive Techniques; Retrospective Studies

This study was aimed at assessing the outcome of in-vitro fertilization (IVF) and embryo transfer in patients with polycystic ovarian syndrome (PCOS). The results of IVF and embryo transfer in PCOS patients (PCOS group, 78 cycles of 26 patients) were compared with those of a control group (423 cycles in 202 patients without male factor; age and ovarian stimulation protocol were matched). Although the pregnancy rate per transfer was not different in the two groups of patients (25 versus 34%, PCOS versus control group), the PCOS group had a significantly lower pregnancy rate per follicle aspiration (19 versus 31%, P < 0.05). A notable result was a significantly higher incidence of embryo transfer cancellations in the PCOS group (22 versus 8%, P < 0.01), which resulted from unpredictable failure of either oocyte recovery or fertilization. The incidence of unexplained complete failure of fertilization was significantly higher in the PCOS group (18 versus 5%, P < 0.01). These results may reflect a reduced quality of the oocytes in the PCOS group, and there was a subgroup of PCOS patients who repeatedly produced poor results of treatment. Although the ovarian stimulation regimen best suited to PCOS patients remains to be determined, special care should be taken during ovarian stimulation, especially when the PCOS patients had experienced unexplained failure of oocyte recovery or fertilization in the previous treatment cycle(s).

Topics: Adult; Embryo Transfer; Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Hormones; Humans; Menotropins; Polycystic Ovary Syndrome; Pregnancy; Pregnancy Rate; Retrospective Studies; Treatment Outcome

Changes in serum immunoreactive (IR)-inhibin were measured by RIA in two studies, in order to elucidate, firstly whether the pattern of IR-inhibin secretion is similar to that of estradiol (E2), and secondly, whether inhibin suppresses endogenous FSH release. Study 1: Purified urinary FSH (pFSH) or human menopausal gonadotropin (hMG) were daily injected intramuscularly into women with hypogonadotropic amenorrhea at 12 to 14 week intervals. PFSH and hMG stimulated IR-inhibin release in a similar fashion in the ovulatory cycles, but the increase in estradiol (E2) during pFSH administration was delayed and lower than that during the hMG cycles. This suggests that E2 and IR-inhibin are secreted independently from the granulosa cells. Study 2: Ovulation induction was performed in 18 cycles of 9 women with polycystic ovarian disease (PCOD) by the step-down administration of pFSH. The serum FSH concentration in cycles with premature LH release increased even after the dose of pFSH was reduced, and were significantly higher than those of cycles without premature LH release. It was also found that the serum IR-inhibin concentration in cycles with the premature LH release was 2 to 4 times as high as in cycles without premature LH release. This suggests that IR-inhibin does not suppress endogenous FSH release associated with premature LH release.

Topics: Adult; Amenorrhea; Chorionic Gonadotropin; Estradiol; Female; Follicle Stimulating Hormone; Humans; Infertility, Female; Inhibins; Luteinizing Hormone; Menotropins; Ovulation Induction; Polycystic Ovary Syndrome

Topics: Clomiphene; Contraceptives, Oral; Drug Therapy, Combination; Female; Glucocorticoids; Gonadotropin-Releasing Hormone; Humans; Infertility, Female; Menotropins; Menstruation Disturbances; Polycystic Ovary Syndrome; Spironolactone

An analysis was performed on the cumulative conception rates, cumulative live birth rates and adverse effects of ovulation induction in patients with anovulatory infertility attending a single unit over an 11-year period. A total of 200 patients were included, 103 with clomiphene-resistant polycystic ovary syndrome (PCOS), 77 with hypogonadotrophic hypogonadism (HH) and 20 with weight-related amenorrhoea (WRA). Ovulation induction was performed using a number of protocols in which pulsatile luteinizing hormone-releasing hormone was administered s.c. or i.v. and gonadotrophins (human menopausal gonadotrophins or follicle-stimulating hormone) were administered i.m. The cumulative conception and live birth rates in the first course of therapy and after 12 cycles of treatment were, respectively, 73.2 and 62.4% in PCOS patients, 82.1 and 65.4% in the HH group and 95.0 and 85.3% in the WRA group. The miscarriage rates for all courses of treatment were 15.5% in PCOS patients, 22.9% in HH patients and 32.3% in WRA patients which resulted in cumulative live birth rates that were not significantly different. The median number of cycles and ovulations to achieve a pregnancy was 2 in all groups. The multiple pregnancy rate was significantly greater in women with PCOS (17.9%) than in women with HH (3.6%, P = 0.0052, 95% CI 5.12-23.36%) but not WRA (3.2%, P = 0.07, 95% CI 4.35-24.92%). The rate of multiple pregnancy fell after the introduction of monitoring by transvaginal ultrasound. Correction of anovulatory infertility by appropriately selected ovulation induction regimens results in cumulative conception and live birth rates indistinguishable from normal.

Topics: Amenorrhea; Anovulation; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Hypogonadism; Infertility, Female; Menotropins; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy; Pregnancy Outcome; Pregnancy, Multiple

To evaluate the role of GnRH administration instead of hCG for triggering follicular maturation in patients with polycystic ovaries (PCO) undergoing hMG ovulation induction when the late follicular 17-beta-E2 levels are > 1,600 pg/mL (> 6,000 pmol/L).. Prospective study.. Infertility outpatient clinic of Rambam Medical Center (general hospital), Haifa, Israel.. High serum E2 concentrations from 1,600 to > 3,600 pg/mL (2,800 +/- 68, mean +/- SD [6,000 to > 13,000 pmol/L, 10,279 +/- 2,500]) were experienced in 44 hMG cycles. The number of preovulatory follicles visualized by transvaginal sonography was between 8 and 25. An IV injection of 200 micrograms GnRH was administered for triggering final follicular maturation and ovulation, instead of 10,000 IU IM hCG, usually injected for this purpose, when the E2 levels are < or = 1,600 pg/mL (6,000 pmol/L). Serum E2 and P levels were monitored in the luteal phase. In cycles where E2 decreased to < or = 1,360 pg/mL (5,000 pmol/L), 2,500 IU hCG was administered once or twice at 3-day intervals for luteal support.. Pregnancy and abortion rates and the rate of ovarian hyperstimulation syndrome (OHSS).. Ten pregnancies were generated by the hMG and GnRH co-treatment in 32 patients (31.2%), in 44 cycles (23%). Two pregnancies aborted (20%), and eight generated eight healthy neonates. Ovarian hyperstimulation syndrome occurred in two cycles of patients who were both pregnant. All but two of these PCO patients also have undergone 69 hMG and hCG cycles. Only 7 patients conceived (23%) 10 times (10/69, 14.5%); 5 of these pregnancies (50%) were multiple gestations (3 twins, 1 sextuplet, and 1 heptuplet gestation). The pregnancy wastage rate was 30% (3/10).. The use of native GnRH to trigger ovulation in PCO patients with late follicular E2 levels > 1,600 pg/mL (6,000 pmol/L) appears to be comparable with prior hMG and hCG cycles in terms of pregnancy rate, pregnancy wastage, risk of multiple gestation, and incidence of severe ovarian hyperstimulation. Unlike hMG and GnRH-agonist, which is associated with luteal phase dysfunction, hMG and GnRH offers a preferable alternative due to the ability of hCG luteal support and rescue, providing the E2 levels are not dangerously increased.

Topics: Estradiol; Female; Gonadotropin-Releasing Hormone; Humans; Medical Records; Menotropins; Osmolar Concentration; Ovarian Follicle; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy; Pregnancy Outcome; Pregnancy, Multiple; Prospective Studies

The luteal phase was studied in 12 polycystic ovary syndrome (PCOS) patients following ovulation induction using exogenous gonadotrophins combined with a gonadotrophin-releasing hormone agonist (GnRH-a). Human menopausal gonadotrophin (HMG) was preceded by 3 weeks of treatment with GnRH-a (buserelin; 1200 micrograms/day intra-nasally) and administered in a step-down dose regimen starting with 225 IU/day i.m. GnRH-a was withheld the day before administration of human chorionic gonadotrophin (HCG; 10,000 IU i.m.). Blood sampling and ultrasound monitoring was performed every 2-3 days until menses. The luteal phase was significantly shorter in PCOS patients as compared to eight regularly cycling controls: 8.8 (3.3-11.4) days [median(range)] versus 12.8 (8.9-15.9) days (P = 0.01). Median peak values for progesterone did not show significant differences comparing both groups: 52.3 (17.1-510.3) nmol/l versus 43.0 (31.2-71.1) nmol/l, respectively (P = 0.8). The interval between the day of the progesterone peak and return to baseline was significantly shorter in the PCOS patients than in controls: 2.5 (0.3-4.9) days versus 4.2 (3.9-10.5) days (P < 0.005). Luteinizing hormone (LH) concentrations during the luteal phase as reflected by area under the curve were significantly lower in PCOS as compared to controls: 4.4 (1.6-21.0) IU/l x days and 49.0 (27.8-79.6) IU/l x days, respectively (P < 0.001). In conclusion, patients with PCOS may suffer from insufficient luteal phases after ovulation induction using HMG/HCG in combination with a GnRH-a. The corpus luteum apparently lacks the support of endogenous LH and may be stimulated only by the pre-ovulatory injection of HCG.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Buserelin; Chorionic Gonadotropin; Drug Therapy, Combination; Female; Follicle Stimulating Hormone; Gonadotropins; Humans; Luteal Phase; Luteinizing Hormone; Menotropins; Ovulation Induction; Polycystic Ovary Syndrome; Reference Values

We conducted a prospective study of blood levels of follicle stimulating hormone (FSH) and luteinizing hormone (LH) following daily intramuscular injection of human menopausal gonadotropin (hMG) containing equal proportions of FSH and LH. Blood samples were collected on alternate days and the resulting changes in the blood levels of the ovarian hormone estradiol were also monitored. Twenty-eight consecutive patients with polycystic ovary syndrome who were between the ages of 25 and 35 years and attending our infertility clinic for ovulation induction therapy and assisted pregnancy were studied. Polycystic ovary syndrome was diagnosed on laparoscopy and as evidenced by high serum LH which was three times greater than FSH in the follicular phase of the menstrual cycle. A male factor for infertility was excluded. Twenty-five out of 28 women (89.3%) receiving hMG responded to therapy by a rise in serum estradiol level (> 1200 pmol/l on day 9). Of the 25 women who responded to hMG, four had live single babies (16%). All four women showed a cumulative rise in mean serum FSH with treatment when measured by standard radioimmunoassay, reaching statistical significance on day 5 (p < 0.05). The remaining 21 who failed to become pregnant showed variable changes in mean serum FSH with a sharp rise on day 3 (p < 0.02) and a significant fall on day 7 (p < 0.02). However, mean serum LH measured by standard radioimmunoassay in all women remained unchanged throughout the period of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Estradiol; Female; Follicle Stimulating Hormone; Humans; Infertility, Female; Luteinizing Hormone; Menotropins; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy; Prospective Studies

To assess the risk of miscarriage after in-vitro fertilization (IVF) with respect to age, cause of infertility, ovarian morphology and treatment regimen, a retrospective analysis was performed of the first 1060 pregnancies conceived between June 1984 and July 1990 as a result of 7623 IVF cycles. Superovulation induction was achieved with human menopausal gonadotrophin (HMG) and/or purified follicle stimulating hormone (FSH) together with either clomiphene citrate or the gonadotrophin hormone-releasing hormone (GnRH) agonist buserelin, the latter either as a short 'flare' regimen or as a 'long' regimen to induce pituitary desensitization. There were 282 spontaneous abortions (26.6%) and 54 ectopic pregnancies (5.1%). The mean age of women with ongoing pregnancies was 32.2 (SD 3.9) years compared with 33.2 (SD 4.1) years in those who miscarried, which were significantly different (P = 0.008). There was no relation between the miscarriage rate and the indication for IVF. The miscarriage rate was 23.6% in women with normal ovaries compared with 35.8% in those with polycystic ovaries [P = 0.0038, 95% confidence interval (CI) 4.68-23.10%]. There was no difference in the miscarriage rate between treatment with HMG or FSH. Women whose ovaries were normal on ultrasound were just as likely to miscarry if they were treated with clomiphene or with the long buserelin protocol. Those with polycystic ovaries, however, had a significant reduction in the rate of miscarriage when treated with the long buserelin protocol, 20.3% (15/74), compared with clomiphene citrate, 47.2% (51/108) (P = 0.0003, 95% CI 13.82-40.09%).

Topics: Abortion, Spontaneous; Adult; Buserelin; Clomiphene; Female; Fertilization in Vitro; Follicle Stimulating Hormone; Humans; Luteinizing Hormone; Menotropins; Pituitary Gland; Polycystic Ovary Syndrome; Pregnancy; Prevalence; Reference Values; Retrospective Studies

To compare the effect of treatment with gonadotropin-releasing hormone agonist (GnRH-a) and human menopausal gonadotropins (hMG) with that of gonadotropins only, on the cumulative livebirth rate and miscarriage rate of pregnancies achieved in women with polycystic ovarian syndrome (PCOS).. Retrospective analysis of the outcome of 97 pregnancies according to the treatment protocol, with or without GnRH-a. Calculation of miscarriage rate and cumulative livebirth rate by life-table analysis.. Infertility clinic and in vitro fertilization (IVF) unit.. Women with polycystic ovaries (n = 239) who were clomiphene citrate failures and received either GnRH-a/hMG (n = 110) or gonadotropins only (n = 129) for ovulation induction (n = 138) or superovulation for IVF (n = 101).. For ovulation induction, hMG was given in a step-up, individually adjusted dose scheme. For IVF, three ampules of pure follicle-stimulating hormone were given for 3 days followed by three ampules per day hMG and then individual dose adjustment. Gonadotropin-releasing hormone agonist (Decapeptyl, D-Trp6, microcapsules, 3.75 mg) was given in a single dose 2 weeks before gonadotropin treatment.. The rate of early miscarriages (< 12 weeks) per pregnancies achieved was analyzed, and the cumulative livebirth rate for each treatment group was calculated by life-table analysis.. Miscarriage rates after treatment in ovulation induction with (16.7%) and without GnRH-a (39.4%) and in IVF with (18.2%) and without GnRH-a (38.5%) were almost identical and were therefore analyzed together. Of pregnancies achieved with GnRH-a, 17.6% miscarried compared with 39.1% of those achieved with gonadotropins alone. Cumulative livebirth rate after four cycles for GnRH-a was 64% compared with 26% for gonadotropins only.. Cotreatment with GnRH-a/hMG for anovulatory women with PCOS reduces the miscarriage rate and improves the livebirth rate compared with treatment with gonadotropins alone.

Topics: Abortion, Spontaneous; Adult; Female; Fertilization in Vitro; Humans; Luteinizing Hormone; Menotropins; Polycystic Ovary Syndrome; Pregnancy; Pregnancy Complications; Retrospective Studies; Triptorelin Pamoate

To examine the relationship of baseline and preovulatory serum E2, P, and LH levels and age with pregnancy outcome in polycystic ovarian syndrome (PCOS) patients undergoing hMG ovulation induction.. Retrospective analysis of all available data over 2 years.. Tertiary referral ovulation induction clinic.. Forty-four anovulatory PCOS patients with 25 ovulatory nonconception and 50 conception cycles after hMG ovulation induction.. Ovulation (midluteal serum P > 25 nmol/L [7.86 ng/mL]); pregnancy (serum beta-hCG > 30 mIU/mL 16 days after ovulating injection); pregnancy outcome: pregnancy termination < 20 weeks' or > or = 20 weeks' amenorrhea.. Of the endocrine parameters considered, none was significantly different in nonconceptive and conceptive ovulatory cycles. Miscarriage was associated with low basal serum E2: median value for pregnancies ending < 20 weeks, 105 pmol/L (28.6 pg/mL) and for > or = 20 weeks 150 pmol/L (40.9 pg/mL). It was also significantly associated with age. For patients > 29.5 years of age, (29.5 years, population mean age) a baseline E2 < or = 140 pmol/L (38.2 pg/mL) had sensitivity 92%, specificity 54%, positive predictive value 65%, and negative predictive value 87% for the prediction of miscarriage. The nature of the previous cycle, the day of the cycle on which therapy commenced, and a past history of miscarriage were not related either to pregnancy outcome or to basal serum E2.

Topics: Abortion, Spontaneous; Adult; Estradiol; Female; Follicular Phase; Humans; Luteinizing Hormone; Maternal Age; Menotropins; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy; Retrospective Studies

Among 30 patients with polycystic ovary syndrome, treated with low-dose gonadotrophins, 75 cycles were analysed in order to characterize overstimulated cycles that were at increased risk of developing ovarian hyperstimulation. Optimal response (one or two follicles > or = 14 mm diameter) was observed in 59 cycles (79%). The remaining 16 cycles (21%) exhibited an overstimulated response characterized either by growing more than two follicles or having an oestradiol level > 850 pg/ml (2 SD above the mean observed in optimal cycles). Six of the latter were handled prospectively when oestradiol levels were found to be too high according to the size of the leading follicle. This stage was termed as developing overstimulation and its identification was based on objective criteria obtained from the optimal group. Following the withholding of gonadotrophin, the follicles continued to grow; however, the final oestradiol level was lower compared with six other matched overstimulated cycles. Overall, 14 patients conceived (47%) of whom three (21%) had multiple pregnancies. Mild or moderate ovarian hyperstimulation syndrome occurred in three cases; all of which involved overstimulated cycles. Low-dose gonadotrophin treatment is associated with a substantial degree of overstimulated response. All cycles should be monitored carefully in order to recognize the overstimulated response, which deserves cautious management.

Topics: Dose-Response Relationship, Drug; Estradiol; Female; Humans; Menotropins; Monitoring, Physiologic; Ovarian Hyperstimulation Syndrome; Polycystic Ovary Syndrome; Prospective Studies; Retrospective Studies; Risk Factors

We studied 23 women with polycystic ovarian syndrome (PCOS), resistant to clomiphene citrate, who had a previous history of multifollicular ovarian development on gonadotrophin stimulation. Each woman had one cycle of gonadotrophin-stimulating hormone agonist/human menopausal gonadotrophin (GnRHa/HMG) stimulation and then one cycle of low-dose follicle stimulating hormone (FSH) stimulation. All GnRHa/HMG cycles were multifollicular. On the low-dose FSH protocol, 10 cycles were unifollicular, while two to three follicles were observed in nine cycles, and four cycles were multifollicular. The ovarian hyperstimulation syndrome ensued in one of the FSH cycles versus 13 of the GnRHa/HMG cycles. Despite decreasing luteinizing hormone (LH) levels and increasing FSH levels, androgen levels increased during stimulation on both protocols. There was one pregnancy in the GnRHa/HMG cycles versus six pregnancies following the FSH cycles. In conclusion, low-dose FSH administration seems a safe stimulation regimen with a satisfactory conception rate even in PCOS women with a previous record of multifollicular ovarian development.

Topics: Estradiol; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Infertility, Female; Luteinizing Hormone; Menotropins; Ovarian Hyperstimulation Syndrome; Polycystic Ovary Syndrome; Pregnancy; Progesterone

Ten patients with polycystic ovary disease (PCOD) had ovulation induction after pituitary suppression by gonadotropin releasing hormone agonist (GnRHa) with GnRHa plus pure follicle-stimulating hormone (FSH) or plus human menopausal gonadotropin (hMG). Duration of the stimulation period and gonadotropin doses were superimposable. A multifollicular response was observed in both treatments. Bioassay and radioimmunoassay of luteinizing hormone, androstanedione and testosterone plasma levels were higher in hMG cycles compared to FSH-treated cycles. No differences was found in FSH and estradiol (E2) plasma concentrations, whereas in hMG-treated cycles the E2/number of follicles and E2/ovarian volume ratios were greater than in the FSH-treated cycles. Clinical results in terms of percentages of ovulation and pregnancies were the same in the two protocols. We conclude that the presence of luteinizing hormone in induction of ovulation in patients with PCOD does not seem to influence follicular recruitment and development, but it may have a role in the enhancement of steroid production.

Topics: Adult; Analysis of Variance; Androstenedione; Anovulation; Biological Assay; Buserelin; Estradiol; Female; Follicle Stimulating Hormone; Humans; Luteinizing Hormone; Menotropins; Ovary; Ovulation Induction; Pituitary Gland; Polycystic Ovary Syndrome; Radioimmunoassay; Testosterone

In view of the association of hyperinsulinemia with elevated luteinizing hormone (LH) levels and hyperandrogenism in polycystic ovary syndrome (PCOS), the effect of octreotide was investigated in women with PCOS. Twelve amenorrheic women were treated with 100 micrograms octreotide twice a day for 7 days; 13 infertile women unresponsive to clomiphene citrate were treated either with octreotide (100 micrograms twice a day from day 1 of the menstrual cycle until corpus luteum formation) in addition to human menopausal gonadotropins (HMG) or with HMG alone. Octreotide significantly reduced the 4-hour integrated LH concentrations. LH pulse amplitude and nadir concentrations, and LH, testosterone, androstenedione, and estradiol responses to a gonadotropin-releasing hormone (GnRH) analogue in amenorrheic PCOS women. Octreotide treatment also resulted in a more "appropriate" hormonal milieu at the time of human chorionic gonadotropin (HCG) injection in the infertile women, with LH and testosterone levels being reduced while follicle-stimulating hormone (FSH) levels increased. Orderly follicular growth occurred, with one or two mature follicles being present at the time of HCG injection in cycles in which octreotide was given together with HMG. There were no cases of hyperstimulation, even in women who had previously hyperstimulated after HMG alone. Octreotide thus inhibits LH and androgen secretion and may improve ovulatory performance in infertile women with PCOS.

Topics: Adolescent; Adult; Amenorrhea; Chorionic Gonadotropin; Female; Follicle Stimulating Hormone; Follicular Phase; Gonadal Steroid Hormones; Humans; Infertility, Female; Injections, Subcutaneous; Luteinizing Hormone; Menotropins; Octreotide; Polycystic Ovary Syndrome

Whereas the dose of hMG is significantly correlated with both BMI and BW, commencing the more obese patient on higher hMG doses is not justified in view of the cancellation of cycles from over-responsiveness in the more obese patients started on higher hMG dosage regimens. If the more obese patient is slow to respond, however, a greater degree of clinical freedom may be exercised to increase the dose. The ultimate outcome of the cycle is not related to BMI, BW, or the dose of hMG used.

Topics: Aging; Body Mass Index; Body Weight; Female; Humans; Menotropins; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy

To assess the effect of moderate obesity on the outcome of induction of ovulation with low dose gonadotrophin in women with polycystic ovary syndrome (PCOS).. Retrospective analysis of women with PCOS treated consecutively. An analysis of the impact of obesity on outcome of pregnancy using data from the North West Thames Regional (NWTR) obstetric database was included for comparison.. Induction of ovulation clinic at the Samaritan Hospital for Women (St. Mary's Hospital Group).. 100 women with clomiphene-resistant anovulation associated with PCOS. 75 were of normal weight (BMI 19-24.9 kg/m2, lean group) and 25 were moderately overweight (BMI 25-27.9 kg/m2, obese group).. Induction of ovulation using low doses of gonadotrophins with small, stepwise increments in dosage as required.. Rates of ovulation, pregnancy and miscarriage; daily and total doses of gonadotrophin required for induction of ovulation.. The proportion of ovulatory cycles was significantly greater in the lean group (77%) compared with the obese group (57%) (chi 2 9.8, P less than 0.001). Obese women required larger doses of gonadotrophin to achieve ovulation (P less than 0.001). The proportion of women who achieved at least one pregnancy was similar in the two groups (39% vs 48%) but miscarriage was more frequent in the obese group (60% vs 27%; P less than 0.05). This difference was independent of the baseline and/or mid-follicular luteinizing hormone (LH) concentration either before or during treatment. Analysis of data from the North West Thames Health Region obstetric database confirmed an increased risk of miscarriage in moderately obese women which was independent of maternal age.. Moderate obesity in women with PCOS, treated with low dose gonadotrophin, is associated with an increased risk of miscarriage. This is reflected in the results of analysis of the effect of obesity on outcome of pregnancy in the general population. It is therefore important to encourage weight reduction in obese women with PCOS before considering therapy to induce ovulation.

Topics: Abortion, Spontaneous; Adult; Drug Administration Schedule; Female; Follicle Stimulating Hormone; Gonadotropins; Humans; Maternal Age; Menotropins; Obesity; Odds Ratio; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy; Pregnancy Complications

Data presented in this study indicate that ovulation can be induced in patients with PCOS using a GnRH analogue combined with hMG in a decreasing dose regimen. Based on the observed decline in functional, medium sized follicles in the late follicular phase, it may be speculated that the risk of ovarian hyperstimulation during gonadotropin induction of ovulation in patients with PCOS can be reduced.

Topics: Adult; Buserelin; Drug Administration Schedule; Female; Follicle Stimulating Hormone; Humans; Infertility, Female; Menotropins; Ovarian Follicle; Ovulation Induction; Polycystic Ovary Syndrome; Random Allocation; Ultrasonography

In an attempt to avoid cancellation, 40 cycles which were biochemically overstimulated with exogenous gonadotrophins (oestradiol level inadvertently exceeding 5400 pmol/l) in 32 patients with polycystic ovarian syndrome, classified as Group II according to the World Health Organization, were managed by a controlled drift period. This involved a schedule where further human menopausal gonadotrophin (HMG) injections were withheld but monitoring continued with daily assays of serum oestradiol and frequent follicular ultrasound examinations. The mean oestradiol level at the start of the drift period was 9249 +/- 3465 (SD) pmol/l and dropped by 64.3 +/- 25.3% to 2945 +/- 1817 pmol/l at the end of 2.8 +/- 1.5 days of drift interval (range 1-8 days) at which time human chorionic gonadotrophin was administered. There was a significant increase in the size of the lead follicle and number of follicles greater than 14 mm in diameter during the drift period. The clinical pregnancy rate per cycle was 25% (10/40). The multiple pregnancy rate was 50% (5/10), and 2.5% (1/40) of the cycles were complicated by severe ovarian hyperstimulation syndrome (OHSS). These data indicate that cycles inadvertently overstimulated with gonadotrophin can be managed with a controlled drift period as an alternative to cancellation, yielding favourable pregnancy rates. The multiple pregnancy rate was 50%, twins in all instances and the rate of severe OHSS was 2.5%, which were within the range reported in the literature for HMG-stimulated cycles.

Topics: Chorionic Gonadotropin; Drug Administration Schedule; Estradiol; Female; Humans; Menotropins; Ovarian Follicle; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy; Pregnancy Outcome; Ultrasonography

Women with anovulation due to polycystic ovary syndrome are likely to develop multiple follicles during gonadotrophin therapy and therefore have a high risk of multiple pregnancy. We have developed a low-dose regimen for use in these women; 100 women with clomiphene-resistant polycystic ovary syndrome were treated. Ninety-five of the women ovulated at least once, 72% of the 401 cycles induced were ovulatory and the majority (73%) of these were uni-ovulatory. The overall cumulative conception rate was 55% at 6 months with only two multiple pregnancies. The rate of early pregnancy loss was 32%, which is similar to that reported by other groups. The prevalence of complications was low with no cases of severe hyperstimulation and less than 5% of cycles were abandoned because of development of multiple follicles. Analysis of baseline and mid-follicular luteinizing hormone levels showed that a raised baseline and/or mid-follicular luteinizing hormone level was associated with a poor response to treatment, i.e. anovulation, ovulation but no conception, or early pregnancy loss. There were no successful pregnancies in the women whose luteinizing hormone levels were persistently raised during ovulatory cycles. Low-dose gonadotrophin therapy is a safe and effective method of inducing ovulation; it is associated with a high incidence of single follicular development and a very low multiple pregnancy rate.

Topics: Clomiphene; Drug Resistance; Female; Follicle Stimulating Hormone; Humans; Luteinizing Hormone; Menotropins; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy; Pregnancy Outcome

Topics: Drug Administration Schedule; Female; Humans; Menotropins; Ovarian Follicle; Ovulation Induction; Polycystic Ovary Syndrome; Pulsatile Flow

In order to improve the ovarian response to exogenous gonadotropins and to reduce the risk of the ovarian hyperstimulation syndrome and of multiple pregnancies, human menopausal gonadotropin (hMG) was administered by continuous pulsatile subcutaneous (s.c.) infusion via a portable pump. The effectiveness of pulsatile hMG treatment was first demonstrated in a control group comprising 7 females with regular ovulatory cycles, who underwent gonadotropin ovarian superovulation and subsequent IVF/GIFT procedures for tubal or male factor. All pulsatile s.c. hMG cycles were ovulatory and one clinical pregnancy was achieved. In this group, ovarian response was similar following intramuscular (i.m.) and pulsatile s.c. hMG therapy, with a marked reduction of preovulatory serum levels of oestradiol in the pulsatile s.c. hMG cycles. In a prospective study, 11 patients with overt polycystic ovary syndrome (PCO) who failed to ovulate in response to clomiphene, received i.m. hMG ovarian superovulation treatment in 19 cycles and pulsatile s.c. hMG in 21 cycles. Following i.m. hMG treatment, only 10 cycles were ovulatory; 7 cycles had to be cancelled for impending ovarian hyperstimulation syndrome. Following pulsatile s.c. hMG treatment, 15 cycles were ovulatory, only 3 treatment cycles had to be disrupted for multifollicular ovarian response. Both modes of treatment were similar in terms of requirement of hMG ampoules, number of preovulatory follicles, preovulatory serum levels of oestradiol and duration of the preovulatory oestradiol rise. The total duration of hMG treatment was significantly increased following pulsatile s.c. hMG. It is concluded, that in overt PCO syndrome, continuous pulsatile s.c. administration of hMG is an effective method to induce follicular maturation and to achieve ovulations.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Dose-Response Relationship, Drug; Drug Administration Schedule; Estradiol; Female; Fertilization in Vitro; Gamete Intrafallopian Transfer; Humans; Infertility, Female; Infusion Pumps; Menotropins; Polycystic Ovary Syndrome; Pulsatile Flow

The aim of human menopausal gonadotropin treatment (hMG), to simulate normal follicular development by injecting FSH and LH and induce follicular rupture with hCG, is rarely met. Multiple follicular development occurs because hypothalamic-pituitary feedback is bypassed. This, exacerbated by the long half-life of hCG, causes the principal complications of hMG therapy--multiple pregnancy and hyperstimulation. The initial use of hMG in pituitary deficiency has been widened to include failure to respond to clomiphene, polycystic ovaries, 'unexplained infertility' and in vitro fertilization. Reported pregnancy rates, incidence of hyperstimulation and of multiple pregnancy vary widely. We reviewed the results of hMG therapy from 1977 to 1989 in 260 consecutive women with clomiphene-resistant infertility. Conception and live birth rates after six treatment cycles were 45.7% and 43.3%, respectively and were influenced by the cause of infertility, age, weight and sperm parameters. The miscarriage rate was 18.6% and multiple pregnancy rate 19.3%. The conception rate fell during the 12-year period in all groups except those with regular anovulatory cycles. Over this period, age, weight and male subfertility increased in patients referred to us. hMG is an effective and safe treatment for women with clomiphene-resistant infertility and patent tubes.

Topics: Adult; Age Factors; Estradiol; Female; Fertilization; Humans; Hypogonadism; Infertility, Female; Menotropins; Obesity; Ovarian Follicle; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy; Progesterone

To attempt the monitoring of ovulation induction solely with ultrasound (US).. Using serial US measurements to monitor ovulation induction using human menopausal gonadotropin and human chorionic gonadotropin (hCG), in comparison with estradiol (E2) concentrations that became available at the end of each cycle.. Specialist Reproductive Endocrine Unit.. Twenty hypogonadotropic and 29 ultrasonically diagnosed polycystic ovary patients.. Follicular growth, uterine measurements, endometrial thickness, and serum E2 concentrations.. Follicular growth, uterine measurements, and endometrial thickness correlated strongly with E2 concentrations (P less than 0.0001). The endometrium on the day of hCG administration was significantly thicker (P less than 0.01) in the conception (n = 27) compared with the nonconception cycles (n = 87), whereas no significant difference were observed in serum E2 concentrations. No pregnancy was observed when hCG had been administered when the endometrial thickness was less than or equal to 7 mm. Midluteal endometrial thickness of greater than or equal to 11 mm was found to be a good prognostic factor for detecting early pregnancy (P less than 0.008).. Serial US examinations used alone have proven to be safe and highly efficient. It also has a unique ability to detect pregnancy in the midluteal phase.

Topics: Adult; Anovulation; Endometrium; Estradiol; Female; Humans; Hypogonadism; Luteal Phase; Menotropins; Monitoring, Physiologic; Ovulation Induction; Polycystic Ovary Syndrome; Prospective Studies; Ultrasonography; Uterus

Seven patients with polycystic ovarian disease (PCO) and having polyfollicular development following ovulation induction by human menopausal gonadotrophin underwent selective follicular reduction by transvaginal ultrasound-guided aspiration of all follicles greater than or equal to 10 mm in diameter leaving two or three preovulatory mature follicles. Twenty-four and 48 h after injection of human chorionic gonadotrophin, the couples had intercourse. Five patients achieved pregnancy in 15 treatment cycles, four in their first cycle after 14 previous unsuccessful stimulation cycles. Four have delivered healthy children: three singletons and one set of twins. One patient spontaneously aborted twins in week 22 of pregnancy. No major complications were encountered. Selective follicular reduction seems to be a possible approach to the treatment of PCO patients having polyfollicular development following ovulation induction.

Topics: Adult; Chorionic Gonadotropin; Female; Humans; Menotropins; Ovarian Follicle; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy; Ultrasonography

Infertile women with oligomenorrhoea and elevated LH concentrations (presumed polycystic ovary disease, PCO) were treated with exogenous gonadotrophins, HMG and HCG, for induction of follicular growth and ovulation, respectively. This was effected in the absence or presence of a gonadotrophin releasing hormone analogue (GnRH-A) to suppress basal LH and the positive feedback surge of LH. Analyses of the duration of HMG therapy required to attain the degree of stimulation for HCG to be administered showed no difference between those with and without LH suppression. Analyses of the ultrasound estimations of rates of follicle growth and continued recruitment during the course of HMG also failed to show any effect of LH suppression. These data show that the high sensitivity of these patients to HMG is not related to the circulating LH concentrations.

Topics: Buserelin; Chorionic Gonadotropin; Depression, Chemical; Female; Humans; Luteinizing Hormone; Menotropins; Ovarian Follicle; Ovary; Polycystic Ovary Syndrome

Two hundred ten treatment cycles of follicle-stimulating hormone (FSH) or human menopausal gonadotropin (hMG) were completed in 49 patients with clomiphene citrate-resistant polycystic ovarian syndrome. The results from 68 cycles of daily intramuscular (IM) FSH and 41 cycles of IM hMG were compared. The ovulation rate, maximum serum estradiol (E2) levels achieved, and pregnancy rate were similar in both groups, but FSH resulted in significantly fewer follicles developing and hyperstimulation. The 68 cycles of daily IM FSH were further compared with the outcome of administering the FSH as an alternate-day IM injection in 70 cycles, and by subcutaneous pulsatile injection in 31 cycles. There were no differences in any of the parameters measured between daily and alternate-day FSH. Pulsatile FSH required a greater total dose over a longer period of time to achieve stimulation. It also produced fewer follicles, a lower maximum serum E2 level, and the lowest incidence of hyperstimulation. Twenty pregnancies resulted, of which 6 aborted in the first trimester; there was 1 set of twins and 13 singleton pregnancies. The cumulative pregnancy rate after 6 treatment cycles was 62%.

Topics: Clomiphene; Drug Administration Schedule; Drug Resistance; Female; Follicle Stimulating Hormone; Humans; Injections, Intramuscular; Life Tables; Menotropins; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy; Pregnancy Outcome

Stimulation with human menopausal gonadotropin (hMG) or follicle-stimulating hormone (FSH) was compared in 34 patients with polycystic ovarian syndrome after pituitary gonadotrope suppression with buserelin acetate. No differences were seen in the hormone parameters observed. Also, the duration of the stimulation period and the dose of gonadotropin used were the same. In both groups a multifollicular response was seen. Oocyte retrieval and in vitro fertilization resulted in identical ratios of mature to total oocytes and cleavage rates. Nine pregnancies occurred, four in the hMG group and five in the FSH group. Of the nine pregnancies, two were the result of transfer of frozen-thawed embryos in estradiol and progesterone substituted cycles.

Topics: Adult; Buserelin; Embryo Transfer; Female; Fertilization in Vitro; Follicle Stimulating Hormone; Gonadal Steroid Hormones; Humans; Menotropins; Ovarian Diseases; Pituitary Gland; Polycystic Ovary Syndrome; Pregnancy

Nineteen women were treated with the gonadotropin-releasing hormone (GnRH) agonist buserelin in order to suppress the pituitary prior to gonadotropin treatment. Eight women were oligomenorrheic, 6 had polycystic ovarian disease (PCOD) and 5 women had normal cycles. Buserelin was administered for 3 weeks before ovarian stimulation, and the pituitary down-regulation was proven by provocative tests. Ovarian stimulation was then achieved by human menopausal gonadotropin (hMG) 2 ampules a day. Several abnormal responses to the combined buserelin/hMG treatment were noted in some patients. This included a sudden decrease in E2 level without LH surge (2 patients), induced follicular growth with buserelin instead of ovarian suppression (2 patients) and ovarian hyperstimulation syndrome in 3 patients with PCOD. From this we conclude that although pituitary suppression can easily be achieved by GnRH analog administration, this does not ensure the prevention of unwanted responses. It is possible that the common denominator for these abnormal responses is that they are ovarian in origin, hence they occur in spite of pituitary down-regulation. Close monitoring of the suppression and stimulation stages will detect most cases of such failures. Furthermore it is possible that not all patients are suitable for the combined treatment of gonadotropin and GnRH agonist.

Topics: Adult; Buserelin; Down-Regulation; Drug Therapy, Combination; Estradiol; Female; Follicle Stimulating Hormone; Humans; Luteinizing Hormone; Menotropins; Oligomenorrhea; Ovary; Ovulation Induction; Pituitary Gland; Polycystic Ovary Syndrome

Twenty-eight hyperandrogenemic women suffering from infertility owing to chronic anovulation were treated with hMG. Only 7 patients exhibited the typical polycystic ovarian appearance of multiple subcortical cysts, however, a wide range (6-15 cm3) of ovarian volume was observed. The LH/FSH ratio was consistently lower than 2.5 and circulating androgens of both ovarian and adrenal origin were elevated. The 4 days dexamethasone suppression test showed more than 80% suppression of dehydroepiandrosterone-sulphate and a variable (40-60%) reduction of testosterone and androstenedione levels. Two different patterns of follicular development were observed in response to hMG. Sixteen patients exhibited polycystic ovarian reaction, whereas 12 women had a follicular growth pattern similar to that seen in hMG-stimulated normo-ovulatory subjects. Patients with polycystic ovarian reaction showed a significantly increased androstenedione response to hMG when compared with the other group. Moreover, the non-stimulated ovarian volume was found to be markedly greater than in subjects without polycystic reaction. Thus, ovarian stimulation of patients with mixed hyperandrogenemia may elucidate the presence of borderline polycystic ovaries; furthermore the increased accumulation of androstenedione may suggest an inherent ovarian failure.

Topics: Adult; Androgens; Androstenedione; Anovulation; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Dexamethasone; Estradiol; Female; Follicle Stimulating Hormone; Humans; Infertility, Female; Luteinizing Hormone; Menotropins; Ovary; Polycystic Ovary Syndrome; Testosterone

The pulsatile subcutaneous administration of human menopausal gonadotropin (hMG) or follicle-stimulating hormone (FSH) was used for induction of ovulation in 26 patients with hypothalamic/pituitary amenorrhea or polycystic ovary syndrome (PCO). Ovulation was observed in 116 (90.6%) of 128 treatment cycles, and 15 (16 treatment cycles) of 26 patients became pregnant. All 14 fetuses, excluding two pregnancies interrupted spontaneously at weeks 6 and 9, were singleton conceptions. Ovarian hyperstimulation was observed in 15.6% of treatment cycles. Five patients with PCO who failed to conceive on the hMG regimen also received pulsatile FSH administration. Although ovulation rates in PCO patients did not differ significantly between the hMG (88.1%) and FSH (88.2%) regimens, a significant reduction in the average dose of FSH (P less than 0.05) was observed with pulsatile FSH administration. Furthermore, the number of patients who conceived during the FSH regimen was significantly greater than that found with hMG treatment. The present data demonstrate that pulsatile subcutaneous administration of hMG or FSH is effective in induction of successful ovulation and establishment of singleton pregnancy in patients with various types of anovulatory infertility.

Topics: Adult; Amenorrhea; Drug Administration Schedule; Female; Hormones; Humans; Infertility, Female; Injections, Subcutaneous; Menotropins; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy; Pregnancy, Multiple; Radioimmunoassay

In the private clinical setting the use of Pergonal or Metrodin is a safe and efficient method of inducing ovulation; however, the known risks of those agents must be kept in mind at all times. By adhering to the guidelines listed here and administering Pergonal and then human chorionic gonadotropin in the prescribed manner, an ovulation rate of greater than 90% should be achieved. A six-month course of therapy with Pergonal should yield a pregnancy rate of 60-70%, provided that the fallopian tubes are normal, the sperm count is adequate and cervical mucus function is intact. Patients who do not become pregnant in six to nine months should be referred to tertiary centers for other procedures, such as in vitro fertilization and/or gamete intrafallopian transfer.

Topics: Chorionic Gonadotropin; Female; Follicle Stimulating Hormone; Humans; Infertility, Female; Male; Menotropins; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy; Private Practice

Topics: Androstenedione; Estradiol; Female; Follicle Stimulating Hormone; Humans; Luteinizing Hormone; Menotropins; Ovulation Induction; Polycystic Ovary Syndrome; Testosterone

Continuous exposure to GnRH eliminates the pituitary as a source of gonadotropins and may have direct suppressive effects on the ovary. A woman with PCO syndrome received leuprolide acetate (1 mg/d SC) for 4 weeks before and simultaneously with hMG stimulation. Human chorionic gonadotropin (5,000 IU) was administered IM on the 8th day of hMG therapy. There were 10 follicles greater than 15 mm and a polycystic appearance to the ovaries with 25 follicles measuring less than 10 mm. The serum E2 concentration was 2,280 pg/mL. She developed severe ovarian hyperstimulation and required hospitalization for 12 days for fluid management. A viable intrauterine pregnancy was present. Four weeks of pretreatment with leuprolide did not prevent hyperstimulation in the presence of an intrauterine pregnancy.

Topics: Adult; Anovulation; Chorionic Gonadotropin; Female; Gonadotropin-Releasing Hormone; Hormones; Humans; Leuprolide; Menotropins; Ovary; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy; Stimulation, Chemical

More than 60% of patients with polycystic ovary disease (PCO) cannot conceive after repeated ovulation inductions with Clomifene citrate although there is ovulation or more frequently follicle luteinization. Because of hyperstimulation, therapy with hMG has been superseded by low doses of purified FSH with variable results according to authors. It has been even claimed that there was no benefit to replace hMG with FSH. However, on the basis of the PCO physico-pathology, namely LH hypersecretion and androgen hyperproduction, it would be rational to associate the desensitization of the pituitary with LH-RH agonist and the ovary stimulation with variable doses of hMG or purified FSH. In the series where such therapy associating LH-RH agonists with purified FSH was applied, the results concerning suppression of LH and androgen secretion, and the occurrence of pregnancy were interesting. However, the risk of hyperstimulation still occurred. Thus, the first part concerns the critical review of these results while, in the second part, our experience in in vitro fecundation will be reported.

Topics: Androgens; Female; Follicle Stimulating Hormone; Humans; Luteinizing Hormone; Menotropins; Polycystic Ovary Syndrome

A standard FSH/hMG stimulation protocol applied to all patients does not yield optimum results. In the Norfolk program it has been found that the determination of FSH/LH ratio on day 3 of the menstrual cycle provides a predictive signal of the likelihood of a good or bad response to a standard protocol. If the FSH is high in relation to LH, the patient will likely be a low responder and/or approaching the menopause. A regime of high-dose pure FSH seems to improve the number of eggs in this group and therefore the pregnancy rate. On the other hand, if the FSH/LH ratio is very low, that is, the patient has a high LH, the patient is generally a high responder and produces many eggs, but in some instances the quality of eggs is suspect, and the pregnancy rate is low in a particular subset of high responders. The use of GnRHa and/or minimal stimulation with FSH or hMG seems to improve the pregnancy rate.

Topics: Female; Fertilization in Vitro; Follicle Stimulating Hormone; Humans; Luteinizing Hormone; Menotropins; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy

The study was designed to examine (1) the effects of the luteinizing hormone releasing hormone (GnRH) agonist, buserelin, on pituitary and ovarian hormone secretion, and (2) the effect that pituitary-ovarian suppression with a GnRH agonist has on subsequent ovulation induction with exogenous gonadotrophins (hMG), in polycystic ovary syndrome (PCOS). Two protocols were studied where buserelin was administered intranasally to all patients in a dose of 200 micrograms, six times daily. Ten patients received buserelin until an oestrogen withdrawal bleed occurred while a further 12 patients received buserelin for 4 weeks, before hMG was co-administered. Nine of the above subjects also underwent conventional ovulation induction with hMG. Blood samples were taken daily for radioimmunoassay of LH (LH-RIA), FSH, sex steroids and inhibin and for immunoradiometric assay of LH (LH-IRMA). Following buserelin administration there was an initial rise in LH-RIA, FSH, oestradiol (E2) and inhibin (P less than 0.01). Fourteen days were needed for LH-RIA to return to the normal range, with both protocols resulting in a fall in LH-RIA and FSH (P less than 0.01) before hMG was co-administered. Twenty-eight days of buserelin administration were needed to suppress E2 into the castrate range. Inhibin and both E2 and FSH were closely correlated throughout buserelin administration (P less than 0.01). There was failure to respond to an intravenous bolus of 100 micrograms of GnRH from 7 days of buserelin administration onwards, despite the serum LH-RIA still being raised at 7 days. Serum samples assayed for LH by RIA using WHO Matched Reagents and by IRMA were closely correlated (r = 0.96, P less than 0.01). There was no difference in the proportion of ovulations (52% vs 66%) or pregnancies (1 vs 1) in the GnRH agonist or control group. Similar amounts of hMG were needed in both groups and there was multiple follicular development (greater than 3 follicles greater than 15 mm diameter; 41% vs 38%) following hMG administration. There was a close correlation between E2 and inhibin levels (P less than 0.01).(ABSTRACT TRUNCATED AT 400 WORDS)

Topics: Administration, Intranasal; Adult; Buserelin; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Gonadotropins; Humans; Inhibins; Injections, Intramuscular; Luteinizing Hormone; Menotropins; Ovary; Ovulation; Pituitary Gland; Polycystic Ovary Syndrome; Radioimmunoassay; Steroids

The treatment course of a 31-year-old infertility patient due to PCO disease is presented. Because the patient failed to conceive after various treatment cycles with CC, she was subjected to a combined GnRHa/hMG/hCG therapy. After plasma E2 levels had reached 2400 pg/ml, three leading follicles, with diameters of 20 to 24 mm, were detected. Induction of ovulation was achieved by 10,000 IU hCG. The patient conceived and developed ovarian hyperstimulation. At 8 weeks of gestation, seven cystic structures were detected within the uterine cavity, five containing single embryos, and two with twin embryos. All nine embryos were vital, as evidenced by their heart beats. Embryo reduction was achieved by transabdominal puncture on three occasions. The three surviving fetuses were carried to the 34th week of gestation. After delivery by cesarean section, three healthy babies developed normally. This communication illustrates the complications that can be associated with ovulation induction in PCO disease: ovarian hyperstimulation, polyovulation, multiple conceptions, and their clinical management.

Topics: Adult; Chorionic Gonadotropin; Female; Gonadotropin-Releasing Hormone; Humans; Infertility, Female; Menotropins; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy; Pregnancy, Multiple; Triptorelin Pamoate

The purpose of this study is to investigate the ovulatory effect of the combined therapy with bromocriptine (Brc), clomiphene (Cl) and HMG. We investigated 25 patients with polycystic ovary syndrome (PCOS) who had anovulatory normoprolactinemia and failed to respond to Cl therapy alone. The results were as follows: 1) The ovulation rate with Method I(Brc/Cl) was 64.0% (16/25) in 25 cases, and 59.8% in 122 cycles. 2) Resting levels of serum dehydroepiandrosterone sulfate in the effective group with Method I were significantly lower than those in the non-effective group. 3) With Method I, serum prolactin (PRL), LH and testosterone were significantly decreased, while estradiol and progesterone concentrations were significantly increased in the effective group. However, there were no significant changes in the hormone levels except PRL in the non-effective group. 4) Out of the 9 nonrespondent Method I cases, 5 additional cases ovulated with both Method II(Brc/Cl+ a small dose of HMG) and Method III(Brc/Cl+ an increased dose of HMG-HCG). The total ovulatory rate was 84.0% (21/25) in 25 cases and 59.4% (85/143) in 143 cycles. 5) The total pregnancy rate was 43.8% (7/16). Six cases were normal pregnancies, one case was a twin pregnancy and there was no case of abortion. Our results suggested that the combined therapy with Brc, Cl and HMG had almost the same therapeutic effect as the HMG-HCG therapy in severe cases of PCOS.

Topics: Adolescent; Adult; Bromocriptine; Clomiphene; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Drug Therapy, Combination; Estradiol; Female; Humans; Menotropins; Polycystic Ovary Syndrome; Prolactin; Testosterone

A patient with PCO and primary infertility had undergone numerous failed attempts of ovulation induction. She then was treated with GnRHa leuprolide 500 micrograms subcutaneously daily for 4 weeks, later combined with hMG 225 IU IM daily for 8 days and hCG 5000 IU IM. Six oocytes were retrieved for IVF, four fertilized and two were replaced. Twin pregnancy was established and delivered at term. Hyperstimulation syndrome was managed conservatively.

Topics: Adult; Chorionic Gonadotropin; Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Hormones; Humans; Infertility, Female; Leuprolide; Menotropins; Ovulation Induction; Polycystic Ovary Syndrome

We studied the value of vaginal progesterone (P4) in suppressing serum LH concentrations and restoring normal luteal phase serum LH concentrations before administration of exogenous gonadotropins in anovulatory women with the polycystic ovarian syndrome (PCOS). P4 (50 mg every 12 h) was administered by vaginal suppository to 9 women (18 cycles) for 14 days before ovulation induction with human menopausal gonadotropin (hMG) and hCG. Serum LH, FSH, estradiol, P4, and PRL levels were measured daily. A biphasic effect on LH secretion occurred during P4 administration. Peak serum LH levels occurred on day 5 (125% of basal levels; P less than 0.05) of vaginal P4 suppository use, followed by a progressive fall (P less than 0.05) to 79% of basal levels, but serum LH levels were still higher than those in normal women despite achieving physiological luteal phase P4 concentrations. Ovulation occurred in 56% of cycles after P4 and hMG/hCG treatment and in 65% of control cycles after hMG/hCG alone. In 7 women, serum LH was measured at 10-min intervals for 6 h before and after vaginal P4 administration for 10 days. LH pulse frequency decreased from 7.4 +/- 1.1 to 4.4 +/- 1.2 pulses/6 h (P less than 0.01), and LH pulse amplitude increased from 3.8 +/- 1.8 to 6.1 +/- 2.9 IU/L (P less than 0.01) after P4 administration. We conclude that vaginal P4 (50 mg every 12 h) 1) produces serum P4 concentrations within the normal range for the luteal phase of the menstrual cycle; 2) elevates serum LH, but not FSH, within 5 days; 3) decreases LH pulse frequency and increases LH pulse amplitude after 10 days, but does not normalize serum LH values; and 5) fails to improve the results of subsequent ovulation induction with exogenous gonadotropins in patients with PCOS.

Topics: Administration, Intravaginal; Adult; Chorionic Gonadotropin; Drug Administration Schedule; Female; Follicle Stimulating Hormone; Humans; Luteinizing Hormone; Menotropins; Ovulation Induction; Polycystic Ovary Syndrome; Progesterone; Prolactin

Ten women of polycystic ovarian-type (PCO-type) anovulation, having a decreased ratio of FSH to LH and androgen excess, resistant to the previous clomiphene, bromocriptine and/or daily im injections of human menopausal gonadotropine (hMG), were treated with continuous sc infusion of 150 IU/day hMG. The treatment was initiated on cycle day 2-5 and continued until the dominant follicle reached 20 mm or more in diameter, when an im bolus of 10,000 IU human chorionic gonadotropin was given. The treatment elevated the geometric mean of pretreatment serum FSH (8.6 mIU/ml) to 15.9 mIU/ml (p less than 0.001), while serum LH decreased from 29.4 mIU/ml to 20.7 mIU/ml (p less than 0.01). This resulted in a highly significant increase in the FSH/LH ratio from 0.29 to 0.77 (p less than 0.0001). Follicle enlargement was demonstrated in 13 of the 14 treatment cycles, 12 of which were ovulatory. Pregnancy ensued in 4 cases, 1 of which was a quadruplet pregnancy. Continuous infusion of hMG was indicated as an effective way of inducing ovulation in PCO-type anovulation resistant to conventional methods of ovulation induction.

Topics: Adult; Androgens; Anovulation; Female; Follicle Stimulating Hormone; Humans; Infusions, Parenteral; Luteinizing Hormone; Menotropins; Ovulation Induction; Polycystic Ovary Syndrome

The ovarian function of infertile women with normal menstrual rhythm was investigated by daily plasma hormone (estradiol, progesterone, luteinizing hormone, and follicle-stimulating hormone) analyses throughout the menstrual cycle, and patients were diagnosed as showing a subnormal profile of progesterone in the early luteal phase or as showing no abnormality. Women with oligomenorrhea and elevated luteinizing hormone levels were diagnosed as having polycystic ovary syndrome primarily on the basis of endocrinology. All patients were treated with a gonadotropin-releasing hormone analog to suppress endogenous luteinizing hormone and follicle-stimulating hormone so that ovulation induction with exogenous gonadotropins could be undertaken as in patients with hypogonadotropic hypogonadism. Interference in the process of ovulation by endogenous luteinizing hormone fluctuations was eliminated and pregnancies were achieved. The pregnancy rate in the group with polycystic ovary syndrome was 77% per treatment course (six cycles) while that in the group with subnormal progesterone profiles was 61.5%. Patients showing no abnormality achieved no pregnancy, demonstrating the redundancy of interference with normal ovarian function.

Topics: Adult; Buserelin; Chorionic Gonadotropin; Drug Therapy, Combination; Female; Humans; Infertility, Female; Luteal Phase; Luteinizing Hormone; Menotropins; Menstrual Cycle; Oligomenorrhea; Ovulation Induction; Polycystic Ovary Syndrome; Progesterone

Selective oocyte retrieval is a new approach to ovarian hyperstimulation (OHS) that prevents side effects of OHS and multiple pregnancies by puncturing most of the ovarian follicles 35 hours after hCG administration as in an IVF program. The remaining intact follicles can still result in a singleton or twin pregnancy. In three patients who presented a multiple follicular development, this technique resulted in two pregnancies; moreover, the retrieved oocytes were fertilized and the embryos frozen.

Topics: Female; Fertilization in Vitro; Follicle Stimulating Hormone; Humans; Menotropins; Oocytes; Ovulation; Polycystic Ovary Syndrome; Superovulation

A combined regimen based on exogenous gonadotropins followed by pulsatile gonadotropin-releasing hormone was attempted in order to induce ovulation in a group of patients with polycystic ovarian disease. The women were selected on the basis of previous unsuccessful treatment with clomiphene citrate, gonadotropin and pulsatile gonadotropin-releasing hormone used separately. At our first attempt at application of this new approach, in all patients follicular growth was recorded and ovulation was induced with exogenous chorionic gonadotropin, without hyperstimulation. Two clinical pregnancies were established. Retrospective hormonal evaluation showed the presence of two premature luteinizations. Pulsatile gonadotropin-releasing hormone administration following follicular recruitment with exogenous gonadotropin may therefore be considered an effective therapy for polycystic ovarian patients resistant to conventional treatment.

Topics: Adult; Drug Administration Schedule; Estradiol; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Luteinizing Hormone; Menotropins; Menstrual Cycle; Ovulation Induction; Polycystic Ovary Syndrome; Progesterone

Eight clomiphene citrate (150 mg/day for 5 days)-resistant anovulatory women with polycystic ovary were included in this study. A luteinizing hormone-releasing hormone (LH-RH) analog, D-Trp-6-LH-RH, 100 micrograms subcutaneous-per day, induced a hypogonadotropic state within varying periods but at most within 3 weeks, after an initial flare-up effect characterized by slight increase in ovarian size in four patients and in the other four by cysts that disappeared rapidly. On the 28th day or 15 to 20 days after menstruation for subsequent cycles, during maintenance of D-Trp-6-LH-RH therapy, a usual gonadotropin regimen was carried out in 33 cycles. Human menopausal gonadotropins obtained follicular maturation in all cycles. However, there was never the growth of a single dominant follicle but always of several follicles. Human chorionic gonadotropin then induced ovulation in 31 cycles (94%). Luteal phase was normal in 28 and inadequate in 3 of the 31 ovulatory cycles. Hyperstimulation, generally mild to moderate but rather severe in 2 cycles, was constant. Five pregnancies were obtained. The overall pregnancy rate was 15% per cycle and 17.8% per normoovulatory cycle. This study showed that an associated treatment with an LH-RH analog enables gonadotropins to achieve ovulation regularly with an encouraging number of pregnancies but at a risk of hyperstimulation.

Topics: Adult; Chorionic Gonadotropin; Clomiphene; Drug Resistance; Female; Gonadotropin-Releasing Hormone; Humans; Infertility, Female; Luteinizing Hormone; Menotropins; Ovarian Follicle; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy; Triptorelin Pamoate

Various treatments have been applied to polycystic ovarian (PCO) type of anovulation. However, none of them was definitive in terms of the efficacy and side effects. Six anovulatory women of PCO type were treated with pulsatile gonadotropin-releasing hormone (GnRH) of various pulse intervals and continuous human menopausal gonadotropin (hMG). The efficacy and rationale of the treatments were discussed. The subjects were diagnosed PCO by GnRH test and/or laparoscopy. They did not ovulate with clomiphene, clomiphene-hCG and hMG-hCG therapies. Their pretreatment serum FSH and LH levels and FSH/LH ratios were 6.9 +/- 1.2 mIU/ml, 15.7 +/- 5.1 mIU/ml, and 0.54 +/- 0.19 (Mean +/- SD), respectively. The treatment consisted of 3 protocols: 1) pulsatile GnRH (5-10 micrograms/pulse) of 90 min interval, 2) pulsatile GnRH (5-10 micrograms/pulse) of 120 min interval and 3) continuous hMG (150 IU/day) through subcutaneous route. Follicular growth was monitored sonographically and an intramuscular bolus of 10,000 IU hCG was given when the dominant follicle reached 20 mm in diameter. During both GnRH treatments serum FSH levels and FSH/LH ratios did not elevate substantially. Serum LH, E2 and PRL levels elevated acutely and transiently during the initial phase of GnRH treatments. Follicular growth was observed in a small fraction of the cases, but none of them ovulated. In contrast, continuous hMG treatment induced significant elevation in serum FSH levels (8.2 +/- 1.7 mIU/ml; p less than 0.01) and FSH/LH ratios (1.73 +/- 0.57; p less than 0.001). Transient hyperprolactinemia was accompanied with the preovulatory E2 rise. All the cases ovulated and 3 singleton pregnancies followed. These findings draw conclusions as follows. Pulsatile GnRH administration may desensitize the pituitary presumably due to increased GnRH pulse frequency as a consequence of two independent pulse generators, intrinsic and exogeneous. It may induce transient hyperprolactinemia through a paracrine system between gonadotrophs and lactotrophs. As a due course pulsatile GnRH therapy is questionable for ovulation induction in cases with functioning hypothalamic-pituitary axis. The fact that continuous hMG effectively induced follicle maturation with elevated FSH/LH ratios suggested that FSH dominance might be a prerequisite for folliculogenesis. The fluctuating nature of gonadotropins might not be mandatory for folliculogenesis.

Topics: Adult; Drug Administration Schedule; Female; Follicle Stimulating Hormone; Humans; Luteinizing Hormone; Menotropins; Ovulation Induction; Pituitary Hormone-Releasing Hormones; Polycystic Ovary Syndrome

Topics: Adult; Buserelin; Chorionic Gonadotropin; Drug Therapy, Combination; Estradiol; Female; Follicle Stimulating Hormone; Humans; Infertility, Female; Luteinizing Hormone; Menotropins; Polycystic Ovary Syndrome

A preparation of HMG purified to contain only FSH (FSH 75 IU/LH less than 1 IU) was used in 26 patients who had anovulatory sterility because of sclero-polycystic ovaries. It was a selected population in that all the patients had proved to be resistant to Clomiphene Citrate and at risk with HMG therapy. Purified urinary FSH was used and monitored as classical HMG treatment. 44 treatment cycles resulted in 33 ovulatory cycles (75%) and 6 pregnancies (13.6% per cycle). The number of cases of hyperstimulation (13.6%) was low when it is compared to situations at risk when HCG was administered in 2/3 of the treatment cycles. The results obtained in a population with a bad prognosis can be considered to be very encouraging and gives purified urinary FSH a specific place in our therapeutic armamentarium.

Topics: Adult; Anovulation; Female; Follicle Stimulating Hormone; Humans; Infertility, Female; Menotropins; Polycystic Ovary Syndrome

Topics: Adult; Androgens; Estrogens; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Luteinizing Hormone; Menotropins; Ovulation Induction; Pituitary Gland; Polycystic Ovary Syndrome

The pulsatile subcutaneous administration of hMG (hMG therapy) and treatment with a combination of luteinizing hormone releasing hormone analogue (Buserelin) and hMG (combined therapy) were used to induce ovulation in 9 patients with polycystic ovary syndrome (PCO). Ovulation was observed in all twelve treatment cycles in the combined therapy, and two cases (delivery at term, and abortion) of pregnancy were confirmed. In the hMG therapy, ovulation occurred in 22 cycles of 26 treatment cycles. Ovarian hyperstimulation occurred in one cycle in the combined therapy and in 5 cycles (3 ovulated patients) in the 26 hMG therapy. The total dose per cycle of hMG required to induce ovulation in the combined therapy (1,700 +/- 203IU) was significantly lower than in the hMG therapy (2,344 +/- 223IU). In response to Buserelin administration, LH and FSH increased transiently and then declined to the normal range observed in the early follicular phase. The reduced LH level was sustained throughout the hMG administration. The concentration of FSH increased in response to hMG administration, resulting in a change in the LH/FSH ratio. The LH/FSH ratio in the combined therapy was significantly lower than in the hMG therapy. The present data demonstrated that pulsatile subcutaneous administration of hMG associated with Buserelin was effective in inducing ovulation in patients with PCO with a low incidence of serious side effects.

Topics: Administration, Intranasal; Adult; Drug Therapy, Combination; Female; Gonadotropin-Releasing Hormone; Humans; Injections, Subcutaneous; Menotropins; Ovulation Induction; Polycystic Ovary Syndrome

Topics: Buserelin; Female; Humans; Infertility, Female; Menotropins; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy

To evaluate the endocrine profiles during induction of ovulation with pulsatile and continuous administration of hMG (Pergonal), 3 patients with polycystic ovarian disease (PCO) and 4 patients with hypothalamic amenorrhea were selected as the subjects. The total dose of hMG per day was 150 IU in each patient. hMG pulse was administered intravenously via a portable infusion pump every 90 min in 4 patients including 3 PCO cases (9.375 IU/pulse) and every 18 min in one patient (1.875 IU/pulse). The remaining 2 patients received continuous subcutaneous infusion of hMG (150 IU/day). Following hMG treatment, 8,000 to 10,000 IU of hCG was used to induce ovulation. All 7 patients ovulated and 4 of them conceived. Pregnancy resulted in 2 patients following pulsatile (every 90 min) administration and in 2 patients after continuous infusion. The duration of hMG treatment needed to induce ovulation was similar among the three modes of administration and within the range of 7 to 10 days. A sustained elevation of circulating FSH levels was observed in all patients and serum estradiol increased more than 3,000 pg/ml in 6 of 7 patients during the course of treatment. Mean (+/- SE) midluteal progesterone level was 107.1 +/- 20.9 ng/ml. Moderate to severe ovarian hyperstimulation occurred in all patients. These results indicate that both pulsatile and continuous administration of hMG are similarly effective in inducing ovulation. They also appear to indicate that the hMG-induced follicular development is profoundly affected by the maintenance of high levels of FSH in the circulation rather than by the mode of administering hMG, whether pulsatile or continuous.

Topics: Amenorrhea; Estradiol; Female; Follicle Stimulating Hormone; Humans; Luteinizing Hormone; Menotropins; Ovulation Induction; Polycystic Ovary Syndrome; Progesterone

Pulsatile administration of human menopausal gonadotropin (hMG) via the subcutaneous route was evaluated in 15 patients with various ovulatory disorders. Administration of hMG was started at a dose of 4.6875 IU (75 IU/day) or 9.375 IU (150 IU/day) per pulse every 90 minutes. Ovulation was observed in 26 (92.9%) of 28 treatment cycles, and two singleton pregnancies were confirmed. Ovarian hyperstimulation was observed in 1 to 26 ovulatory cycles; however, no other side effects were observed during treatment. A regimen of 75 IU/day resulted in a significant increase (P less than 0.0001) of the total dose and prolongation of the treatment period for induction of ovulation, as compared with that of 150 IU/day. Shortened luteal phases occurred in ovulatory cycles induced by pulsatile subcutaneous treatment. Human chorionic gonadotropin administration given every other day until the midluteal phase significantly prolonged the duration of the luteal phase (P less than 0.05). This treatment in patients with the polycystic ovary syndrome was followed by a normalization of luteinizing hormone/follicle-stimulating hormone ratio and resulted in a successful induction of ovulation in 8 to 10 cycles. The present data demonstrated that pulsatile subcutaneous administration of hMG was effective in inducing follicular maturation and ovulation in patients with various types of anovulatory infertility.

Topics: Adult; Amenorrhea; Anovulation; Drug Administration Schedule; Female; Gonadal Steroid Hormones; Gonadotropin-Releasing Hormone; Gonadotropins, Pituitary; Humans; Hypothalamic Diseases; Infertility, Female; Injections, Subcutaneous; Luteal Phase; Menotropins; Ovulation Induction; Polycystic Ovary Syndrome

A 31-year-old woman is described with PCOD associated with endometrial hyperplasia and well-differentiated adenocarcinoma. Conservative treatment with ovulation induction was pursued for a total of 3 1/2 years. After CC treatment failed to achieve conception, treatment with menotropins resulted in a twin pregnancy that aborted spontaneously and a singleton term pregnancy. Hysterectomy was performed 4 1/2 years after the initial diagnosis of well-differentiated endometrial adenocarcinoma was made. Histologic examination of the endometrium showed no progression of the disease. Ovulation induction of patients with polycystic ovaries and well-differentiated and noninvasive endometrial adenocarcinoma may be justified in properly selected cases.

Topics: Adenocarcinoma; Adult; Endometrial Hyperplasia; Female; Humans; Infertility, Female; Menotropins; Ovulation Induction; Polycystic Ovary Syndrome; Uterine Neoplasms

Topics: Buserelin; Chorionic Gonadotropin; Drug Therapy, Combination; Estradiol; Female; Humans; Infertility, Female; Luteinizing Hormone; Menotropins; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy; Progesterone

The incongruity between oestrogen elevation and immature follicles is one of the problems encountered during the induction of ovulation with gonadotrophins. This phenomenon is particularly pertinent in women with polycystic ovarian disease. Our work presents a regimen of treatment that was found helpful in overcoming this problem. It is based on a close ultrasonic assessment of the follicular growth, which also serves as the sole means for the decision of human chorionic gonadotrophin (HCG) administration (mature follicle range is 19-25 mm). Accordingly, the human menopausal gonadotrophin doses were individually adjusted and, if necessary, omitted in an effort to avoid excessive oestrogen elevation at the time of HCG administration. The resultant plateau or decline of oestrogen levels in our series do not interfere with ovulation. Seventeen conceptions occurred after 53 treatment cycles in 19 women.

Topics: Adult; Chorionic Gonadotropin; Estradiol; Female; Humans; Menotropins; Ovarian Follicle; Ovulation Induction; Polycystic Ovary Syndrome

The endocrine effects of induction of ovulation with menotropins were studied in 43 patients: 11 with hypothalamic amenorrhea and 32 with the polycystic ovary syndrome. Patients with polycystic ovary syndrome had higher base-line values of serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), 17 beta-estradiol, dehydroepiandrosterone sulfate, testosterone, and a higher testosterone-free index than those with hypothalamic amenorrhea. During treatment with menotropins, patients with polycystic ovary syndrome had higher values of serum LH, prolactin, dehydroepiandrosterone sulfate, testosterone, percent free testosterone, testosterone-free index, and body weight than those with hypothalamic amenorrhea; serum FSH, dose of menotropins per kilogram body weight, and total follicular volume were higher in patients with hypothalamic amenorrhea than in those with polycystic ovary syndrome. Multiple linear regression after log transformation demonstrated that the testosterone-free index was predicted statistically by total ovarian volume and dehydroepiandrosterone sulfate and that serum 17 beta-estradiol was predicted statistically by total ovarian volume and testosterone-free index. Adding dexamethasone to menotropins in six patients with polycystic ovary syndrome produced significant decreases in 17 beta-estradiol, dehydroepiandrosterone sulfate, testosterone, and testosterone-free index. Higher concentrations of endogenous serum LH and dehydroepiandrosterone sulfate in patients with polycystic ovary syndrome in comparison with those with hypothalamic amenorrhea were associated with higher concentrations of serum testosterone, a lower total follicular volume, and an effective response to menotropins at a lower serum FSH and a lower dose of menotropins per kilogram body weight. These data suggest that serum dehydroepiandrosterone sulfate may be a precursor for ovarian steroidogenesis.

Topics: Adrenal Glands; Amenorrhea; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Dexamethasone; Estradiol; Female; Follicle Stimulating Hormone; Humans; Luteinizing Hormone; Menotropins; Ovary; Ovulation Induction; Polycystic Ovary Syndrome; Prolactin; Testosterone

Topics: Adult; Female; Follicle Stimulating Hormone; Humans; Menotropins; Ovulation Induction; Polycystic Ovary Syndrome

Topics: Adult; Female; Gonadotropin-Releasing Hormone; Humans; Luteinizing Hormone; Menotropins; Polycystic Ovary Syndrome

In patients with polycystic ovarian disease (PCOD) ovulation was induced with a combination of human menopausal gonadotropin (hMG) and human chorionic gonadotropin (hCG) or with urinary follicle-stimulating hormone (uFSH; Metrodin, Serono Laboratories, Inc., Randolph, MA) alone. hMG/hCG and uFSH resulted in comparable rates of ovulation and conception in patients with PCOD. The incidence of hyperstimulation and the potential for multiple births appeared lower with uFSH. The fact that endogenous ovulation did not occur in hMG patients who had hCG withheld or in 3 of the 11 uFSH patients who had preovulatory levels of estradiol and follicles greater than 15 mm may imply that these similarly derived gonadotropins in some instances block endogenous ovulation.

Topics: Androstenedione; Chorionic Gonadotropin; Estradiol; Estrone; Female; Follicle Stimulating Hormone; Humans; Luteinizing Hormone; Menotropins; Menstrual Cycle; Ovulation Induction; Polycystic Ovary Syndrome; Testosterone

Human urinary FSH (HU-FSH) was administered during 25 treatment cycles to 21 infertile women with polycystic ovary syndrome (PCO) who had failed to conceive in response to clomiphene citrate. HCG was also given in 23 of the cycles. Twenty-two (88%) ovulations occurred, and eight (38.1%) conceptions resulted, two (25%) of which terminated in abortion and six (75.0%) in normal deliveries. No multiple pregnancies occurred. Ten instances (40%) of mild-moderate hyperstimulation also resulted. A spontaneous LH surge was observed in 12 treatment cycles. Ultrasound scanning revealed multiple ovarian follicles developing at various rates. We conclude that HU-FSH is an effective form of treatment for women with PCO. However, the response to exogenous FSH is unpredictable and depends on the stage of development and the number of follicles present prior to stimulation.

Topics: Chorionic Gonadotropin; Female; Gonadal Steroid Hormones; Humans; Infertility, Female; Menotropins; Ovary; Ovulation; Polycystic Ovary Syndrome; Prolactin; Ultrasonography

A high incidence of premature labor, incompetent cervix and fetal wastage occurs in multiple gestations which follow treatment with human menopausal gonadotropins (HMG). In order to determine the effect of treatment with HMG on hormone secretion in human pregnancy, progesterone (PROG), 17 beta-estradiol (E2), estriol (E3) and human chorionic gonadotropin (hCG) were determined by radioimmunoassay in 341 serum specimens from 229 normal singleton pregnancies and in 79 serum specimens from 20 pregnancies following induction of ovulation with HMG in women with either hypothalamic amenorrhea (HA) or the polycystic ovary syndrome (PCO). Fitting equations were found for the log transformed normal values and the residuals were obtained by subtraction of the predicted normal values from the log transformed values observed in the HMG pregnancies. In pregnancies which followed treatment with HMG, PROG and E2 were initially elevated above normal. As pregnancy progressed, the deviation from normal became proportionately less. PROG (P less than 0.025) was lower and E2 (P less than 0.025) and E3 (P less than 0.05) were higher in PCO pregnancies than in HA pregnancies. Multiple gestation produced increases in PROG (P less than 0.005), E2 (P less than 0.005) and E3 (P less than 0.001) in comparison to singleton pregnancies.

Topics: Amenorrhea; Chorionic Gonadotropin; Estradiol; Estriol; Female; Humans; Menotropins; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy; Pregnancy, Multiple; Progesterone; Statistics as Topic; Time Factors

Ovarian hyperstimulation syndrome occurred after induction of ovulation with menotropins (follicle-stimulating hormone and luteinizing hormone) and implantation of an intrauterine pregnancy. Serial determinations of aldosterone, deoxycorticosterone, 17 beta-estradiol, progesterone, human chorionic gonadotropin, urinary and plasma electrolytes, and fluid balance were obtained. Plasma renin activity, aldosterone, deoxycorticosterone, and antidiuretic hormone rose markedly. Hydration for four days improved urinary output but also accelerated sodium and fluid retention. Subsequent restriction of salt and water stabilized the patient. Spontaneous abortion was followed by prompt diuresis without a change in therapy. Regression analysis of the authors' data, the clinical observations, and other data in the literature suggest that the ovarian hyperstimulation syndrome is produced by excessive secretion of an unknown hormone that regulates peritoneal fluid during the normal menstrual cycle, and that elevations of plasma renin, aldosterone, and antidiuretic hormone are secondary.

Topics: Adult; Aldosterone; Anovulation; Chorionic Gonadotropin; Desoxycorticosterone; Electrolytes; Female; Humans; Menotropins; Ovarian Follicle; Ovary; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy; Progesterone; Ultrasonography; Water-Electrolyte Balance

A long-acting agonist of gonadotropin-releasing hormone (GnRH-a, 100 micrograms/day) was administered daily for 14 days in four patients with polycystic ovarian disease (PCOD) and eight ovulatory women (OW) to determine acute hormone responses. Initiation of GnRH-a treatment in OW on day 5 of their menstrual cycles (OW-day 5) stimulated a greater acute rise of serum follicle-stimulating hormone (FSH) than that seen in OW beginning treatment on day 2 (OW-day 2) or PCOD patients. FSH levels fell to baseline values with repeated injections, whereas luteinizing hormone levels remained elevated in all patients. An acute rise and progressive fall of estradiol (E2) was found in all groups. The OW-day 5 group demonstrated a secondary increase, which by day 14 was clearly greater than that found in the other groups. This secondary increase of E2 in the OW-day 5 group was associated with lower abdominal pain, whereas OW-day 2 and PCOD patients were asymptomatic. For comparison, human menopausal gonadotropin (150 IU/day for 3 days) stimulated a significantly greater increase of E2 in OW-day 5 than in PCOD patients. These studies indicate that daily GnRH-a administration induced variable effects on ovarian function, which depended on when it was begun during the menstrual cycle and whether it was given to ovulatory or PCOD subjects. In addition, abdominal discomfort associated with GnRH-a use in regularly OW can be avoided by commencing agonist administration earlier in their menstrual cycles.

Topics: Abdomen; Estradiol; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Hormones; Humans; Luteinizing Hormone; Menotropins; Menstrual Cycle; Ovary; Ovulation; Pain; Polycystic Ovary Syndrome; Time Factors

Five infertile patients with polycystic ovarian disease were treated to induce ovulation with pure human urinary follicle-stimulating hormone and human menopausal gonadotropin consisting of follicle-stimulating hormone and luteinizing hormone in 1:1 ratio. No substantial differences were seen between the two types of treatment regarding plasma values of follicle-stimulating hormone, prolactin, testosterone, dihydrotestosterone, progesterone, and 17-hydroxyprogesterone. Estrone, estradiol, and androstenedione values were higher during human urinary follicle-stimulating hormone treatments. Luteinizing hormone levels dropped in both treatments, but the fall was greater during human urinary follicle-stimulating hormone. No real differences were observed concerning number of ovulations, length of treatments, and follicle-stimulating hormone amounts administered; no hyperstimulations were observed. These data do not confirm the observation that more controlled responses of the ovaries can be elicited when low luteinizing hormone gonadotropin preparations are used.

Topics: Androgens; Drug Evaluation; Estradiol; Estrone; Female; Humans; Luteinizing Hormone; Menotropins; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy; Ultrasonography

Statistical evaluation of 133 cycles of induction of ovulation using generalized linear models demonstrated that the occurrence and severity of ovarian hyperstimulation was influenced by the serum 17 beta-estradiol (E2) concentration (P less than 0.001), conception (P less than 0.001), and the endocrinologic diagnosis, polycystic ovary syndrome (PCO) or hypothalamic amenorrhea (HA) (P less than 0.01). When menotropins were administered between 5:00 P.M. and 8:00 P.M. and blood was drawn at 8:00 A.M., an upper limit for serum E2 in patients with HA of 2417 pg/ml or an upper limit for patients with PCO of 3778 pg/ml gave an approximate 5% risk of severe ovarian hyperstimulation in conception cycles and a 1.3% risk of severe hyperstimulation in nonconception cycles. Comparison of our E2 radioimmunoassay involving extraction and chromatography to the Pantex immunodirect Estradiol 125I kit (Pantex, Santa Monica, CA) demonstrated no detectable systematic error, allowing the use of these limits with either assay. The ovulating injection of human chorionic gonadotropin was given at 5:00 P.M. to 8:00 P.M. on the evening of blood drawing as soon as the first follicle reached an average diameter of 14 mm or greater. The ultrasound parameters allow the chance of pregnancy to be optimized and the chance of multiple gestation to be minimized. Serum E2 monitoring indicates when the risk of ovarian hyperstimulation is too great for human chorionic gonadotropin to be given.

Topics: Amenorrhea; Chorionic Gonadotropin; Chromatography; Estradiol; Female; Humans; Hypothalamic Diseases; Infertility, Female; Iodine Radioisotopes; Menotropins; Models, Biological; Ovary; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy; Radioimmunoassay; Time Factors

A comparison of peripheral patterns of androstenedione (A), 17 beta-estradiol (E2) and progesterone (P) is reported in ten infertile women during HMG-HCG induction of ovulation, in order to assess the site of ovarian secretion of plasma A and the possible influence on conception. Evidence for both the follicular and luteal secretion of plasma A is suggested, in addition to the stromal and adrenal contributions, since a highly significant (p less than 0.001) correlation between A and E2 plasma levels was shown during the treatment. In three cycles of conception, plasma A showed a periovulatory peak and drop, followed by a luteal increase, all of which are characteristic of E2.

Topics: Adult; Amenorrhea; Androstenedione; Animals; Anovulation; Chorionic Gonadotropin; Estradiol; Female; Humans; Menotropins; Ovulation Induction; Polycystic Ovary Syndrome; Progesterone; Rabbits

Correlation coefficients for dehydroepiandrosterone sulfate (DHEAS) were determined in women on menotropin. DHEAS was significantly correlated with testosterone free index (TFI), 0.78**; percentage free testosterone (%FT), 0.66**; androstenedione (delta 4A), 0.66*; luteinizing hormone (LH), 0.55**; LH/follicle-stimulating hormone (FSH) ratio, 0.55**; 17-OH-progesterone (17-P), 0.55**; testosterone (T), 0.53**; weight (WT), 0.40**, urinary estriol glucuronide (E3G), 0.33*; and free cortisol index (FFI), 0.32*, with 43 df but not with prolactin (PRL), 0.25. Normal male DHEAS (3.5 +/- 1.2, 25) (microgram/ml; mean +/- standard deviation, n) was higher than normal female DHEAS (2.4 +/- 1.1, 27), P less than 0.01 and DHEAS in women on oral contraceptives (1.9 +/- 1.1, 17) was slightly lower than in normal females, P greater than 0.2. In the combined population (male, female, and females on oral contraceptives) DHEAS was correlated with TFI (0.56**), T (0.54**), %FT (0.52**), delta 4A (0.40**), and age (-0.40**) with 66 df and 17-P (0.30*) with 54 df. TFI appears to be one determinant of plasma DHEAS, **P less than 0.01. *P less than 0.05.

Topics: Amenorrhea; Dehydroepiandrosterone; Female; Humans; Infertility, Female; Luteal Phase; Menotropins; Polycystic Ovary Syndrome; Testosterone

Twenty-four women with ovulatory infertility as a result of surgically or biochemically documented polycystic ovary syndrome (PCO) who had failed to conceive during clomiphene citrate therapy underwent a closely supervised menotropin treatment to induce ovulation. Evidence of ovulation was obtained in all patients treated, and major side effects were limited. Fourteen women conceived after an average of 2.4 treatment cycles; twin pregnancies occurred in 36% and spontaneous abortions occurred in 21%. Initial treatment cycles tended to be less successful than the subsequent treatment cycles. Serum 17 beta-estradiol (E2) levels were significantly augmented in the last 3 days before administration of chorionic gonadotropins (hCG) in treatment cycles resulting in conception compared to E2 levels in those cycles which resulted in ovulation only. A second hCG administration to trigger ovulation had to be given in 27% of the treatment cycles and seemed to be an indication of a less promising treatment cycle. Treatment cycles resulting in twin gestations did not differ from those resulting in singleton gestations; specifically, the E2 response was not increased. In summary, under a closely monitored regimen, menotropin therapy can be used in women with nonovulatory infertility as a result of PCO with considerable effectiveness and relative safety once clomiphene citrate treatment has failed.

Topics: Abortion, Spontaneous; Adult; Chorionic Gonadotropin; Estradiol; Female; Fertilization; Humans; Infertility, Female; Menotropins; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy; Pregnancy, Multiple; Twins

Menotropins (human menopausal gonadotropin [hMG]) are used to induce follicular maturation and ovulation in anovulatory infertile women. To determine how hMG stimulation affected ovarian androgen production during such therapy, plasma androstenedione (A) and testosterone (T) levels were measured at the beginning and end of hMG therapy in 5 patients with anovulatory hypogonadotropism (group 1) and 15 patients with anovulatory polycystic ovary syndrome (group 2). Mean pretreatment levels of plasma estradiol (E2), T, and A were significantly higher in group 2 compared with group 1. Stimulation with hMG caused E2 levels to reach the same maximum value in both groups. Testosterone levels increased from 0.2 +/- 0.03 ng/ml (mean /+- SE) to 0.4 %/- 0.038 ng/ml for group 1 patients, and from 0.53 +/- 0.06 ng/ml to 0.8 +/- 0.1 ng/ml for group 2 patients. Androstenedione levels increased from 1.5 +/- 0.47 ng/ml to 2.1 +/- 0.4 ng/ml and from 4.37 +/- 0.77 ng/ml to 5.8 +/- 1.1 ng/ml in groups 1 and 2, respectively. The influence of hMG on plasma androgen levels was studied in women who received several treatment cycles before they became pregnant. In these women plasma androgen levels reached the same values in all cycles, including the final cycle in which the patient became pregnant. The data indicate that patients treated with hMG become pregnant despite marked gonadal androgen production. These observations suggest that hMG therapy promotes steroidogenesis in both the granulosa and theca cells of the follicle.

Topics: Androstenedione; Anovulation; Estradiol; Female; Fertilization; Humans; Menotropins; Ovary; Polycystic Ovary Syndrome; Pregnancy; Stimulation, Chemical; Testosterone

During the years 1974 to 1977, a total of 77 treatment cycles of human menopausal gonadotropin (hMG)-human chorionic gonadotropin (hCG) were administered to 41 infertile patients with polycystic ovarian disease who failed to conceive on clomiphene. Twenty-seven patients (65.9%) conceived, two of them twice, making twenty-nine pregnancies. The abortion rate was 24.1% and the multiple pregnancy rate was 36.3%. Of the 77 treatment cycles, 7.8% were complicated by mild hyperstimulation and 3.9% by severe hyperstimulation. In six treatment cycles (7.8%), ovulation occurred spontaneously prior to the hCG injection. hMG-hCG is an additional safe and effective, nonsurgical treatment for women with polycystic ovarian disease who have failed to respond to clomiphene therapy. The reaction to exogenous gonadotropins is unpredictable and probably depends on the stage of follicular development prior to the stimulation. Therefore, daily estrogen determinations from the 1st day of treatment are mandatory in order to avoid hyperstimulation and/or multiple births.

Topics: Adult; Body Temperature; Chorionic Gonadotropin; Clomiphene; Estradiol; Female; Humans; Hypertrophy; Infertility, Female; Menotropins; Ovary; Ovulation; Polycystic Ovary Syndrome; Pregnancy; Pregnancy, Multiple

Topics: Adult; Chorionic Gonadotropin; Dose-Response Relationship, Drug; Estrogens; Female; Follicle Stimulating Hormone; Humans; Infertility, Female; Insemination, Artificial, Homologous; Luteinizing Hormone; Menotropins; Menstruation; Polycystic Ovary Syndrome; Pregnancy

Urinary excretion of oestrogens in response to stimulation with a standardized dose of gonadotrophin has been used previously in the differential diagnosis of oligomenorrhoea/amenorrhoea. Patients with polycystic ovarian disease were said to have a characteristic excessive response. In the present study, some patients with laparoscopically proven polycystic ovaries did not show such an excessive response, while others with laparoscopically normal ovaries did. A high LH/FSH ratio correlated well with the laparoscopic finding of polycystic ovaries. It is concluded that where there are adequate facilities for diagnostic laparoscopy and determination of plasma gonadotrophins, there is no further place for the routine use of the standardized gonadotropin stimulation test in the evaluation of suspected polycystic ovarian disease.

Topics: Adult; Estrogens; Female; Follicle Stimulating Hormone; Humans; Luteinizing Hormone; Menotropins; Polycystic Ovary Syndrome; Prolactin; Testosterone

Gonadotropin and steroid hormone levels in both peripheral and ovarian venous blood were measured in samples obtained from 20 Japanese patients with polycystic ovary syndrome (PCOs) and 10 normal women in early follicular phase (normal women) by radioimmunoassay. The change in the amount of steroid hormone following intravenous human menopausal gonadotropin (HMG) or dexamethasone administration was investigated. The mean concentration in patients with PCOs was significantly higher than the concentrations found in normal women for LH (p less than 0.001), but not for FSH in peripheral blood. Significantly elevated ovarian venous steroid hormone levels in PCOs were found for 17 alpha-hydroxypregnenolone (p less than 0.05), progesterone (p less than 0.05), 17 alpha-hydroxyprogesterone (p less than 0.01), 4 delta-androstenedione (p less 0.01), testosterone (p less than 0.01), estrone (p less than 0.01) and estradiol (p less than 0.05), but not for dehydroepiandrosterone-sulfate (DHEAS). The ovarian dehydroepiandrosterone (DHEA) level was slightly elevated in PCOs. The concentration of ovarian 4 delta-androstenedione in PCOs reached twelve times as much as that in normal women. After the administration of HMG, all of the ovarian venus steroid hormone levels were elevated slightly and without significance in the short observation time for 10 min. The DHEAS level was suppressed while the ovarian DHEA level remained high in PCOs following dexamethasone administration. These findings seem to indicate there is no adrenal involvement and no adrenal-like component in the ovary of PCOs, and no evidence of 3 beta-hydroxysteroid dehydrogenase and/or aromatase deficiency in this study. The increase in the steroid hormone secretion in PCOs is explained by the increase in ovarian production in polycystic enlarged ovaries.

Topics: Adult; Dexamethasone; Female; Follicle Stimulating Hormone; Hormones; Humans; Luteinizing Hormone; Menotropins; Ovary; Polycystic Ovary Syndrome; Radioimmunoassay

Ultrasonic monitoring of ovarian follicles and estimation of serum estradiol were carried out in 12 patients with clomiphene therapy, in 5 patients with gonadotropin therapy, and in 7 normal controls. The average diameter of preovulatory follicles in normal controls was 12,8 mm; in ovulation induction groups it was 2 to 4 mm greater. The level of serum estradiol was also higher in ovulation induction groups than in normal controls. The combined use of these two methods is recommended: ultrasonic monitoring to minimize the risk of multiple pregnancies and estrogen level monitoring to minimize the risk of hyperstimulation. Ultrasound is also safe and practical in following the size of hyperstimulated ovaries.

Topics: Clomiphene; Female; Humans; Menotropins; Ovulation Induction; Ovum; Polycystic Ovary Syndrome; Pregnancy; Ultrasonics

Seventy seven cases of micropolycystic ovaries were reviewed. All of the patients underwent either coelioscopy or wedge resection of the ovaries. It was thus possible to classify the patients into two groups on the basis of the size of the ovaries (MPCO-A, large ovaries, more than twice the normal size; MPCO-B, ovaries only slightly increased in size or normal). There were differences from a clinical, laboratory and therapeutic standpoint. In MPCO-A, spaniomenorrhea predominated, clinical hyperandrogenism was often absent and 17 ketosteroids lower. Response to hypothalamic gonadotrophic hormone liberation factor was explosive in luteotrophic hormone, but at 120 minutes levels were lower in MPCO-A than in MPCO-B. Wedge resection failed completely in 23% of cases of MPCO-A and in 66% of cases of MPCO-B. This study confirmed current concepts of the heterogeneity of MPCO syndrome.

Topics: 17-Ketosteroids; Female; Gonadotropin-Releasing Hormone; Humans; Luteinizing Hormone; Menotropins; Polycystic Ovary Syndrome; Testosterone

Ten infertile patients with polycystic ovarian disease were treated with 18 cycles of "pure" human pituitary follicle-stimulating hormone (HP-FSH) and 10 cycles of human menopausal gonadotropin (HMG) consisting of FSH and luteinizing hormone (LH) in a 1:1 ratio. Human chorionic gonadotropin was used to trigger ovulation when optimal follicular development was achieved as judged by urinary estrogen determinations. Of the 18 cycles utilizing HP-FSH, 14 were presumptively ovulatory, 2 were conceptual, and in 5 cycles ovarian enlargement was noted. Of the 10 HMG cycles, none was ovulatory, no conceptions resulted, and 6 instances of hyperstimulation were noted. Pretreatment serum LH levels were significantly higher than normal follicular phase values. These observations suggest that endogenous LH levels in patients with polycystic ovaries are quite adequate for follicular development so that the administration of exogenous LH is unwarranted. Furthermore, the data suggest that HP-FSH or low-LH-containing HMG may prove to be an additional safe and effective nonsurgical treatment modality for patients who are anovulatory because of polycystic ovaries.

Topics: Adult; Estrogens; Female; Follicle Stimulating Hormone; Humans; Infertility, Female; Menotropins; Ovulation Induction; Polycystic Ovary Syndrome

Topics: Adult; Chorionic Gonadotropin; Clomiphene; Cortisone; Drug Therapy, Combination; Female; Humans; Menotropins; Ovary; Polycystic Ovary Syndrome

Ovulation has been induced by clomiphene citrate and human gonadotropins in infertile women. Clomiphene should be the first choice in anovulatory women with active ovaries as indicated by basic levels of estrogens in blood or urine, in women with post-pill amenorrhea even if their ovaries are quiescent and in women with functional abnormalities of the hypothalamus or pituitary. Human gonadotrophins should be used as a second alternative when clomiphene fails. It should also be used as a first choice in women with primary amenorrhea and quiescent ovaries and in women with gross anatomical changes in the pituitary or hypothalamus. If no result is obtained after two courses of gonadotropic therapy, further treatment should be reconsidered and the infertile couple reinvestigated.

Topics: Adult; Amenorrhea; Anovulation; Clomiphene; Female; Follicle Stimulating Hormone; Gonadotropins, Pituitary; Humans; Infertility, Female; Menotropins; Polycystic Ovary Syndrome; Pregnancy

Serum testosterone levels were monitored in female subjects who received therapy with human gonadotropins of urinary origin (menotropins) and human chorionic gonadotropin (hCG). Serum testosterone levels were not elevated in those subjects who did not experience side effects with therapy (Group A); among the other 7 subjects (Group B) with either moderate or severe ovarian hyperstimulation, serum testoterone levels rose distinctly (range 1.4 minus 9.0 ng/ml). Total menotropin dosage and serum estradiol-17beta levels were higher in Group B than in Group A. Ovarian hyperstimulation and elevation of serum testosterone were not restricted to patients with the syndrome of polycystic ovaries.

Topics: Chorionic Gonadotropin; Estradiol; Female; Follicle Stimulating Hormone; Humans; Luteinizing Hormone; Menotropins; Ovarian Diseases; Ovary; Polycystic Ovary Syndrome; Progesterone; Testosterone

We report the results obtained with a standard system of gonadotrophin therapy. Seventy-seven consecutive patients were given 322 treatment cycles. Thirty-seven patients (48 per cent) conceived, six of them on two occasions, making 43 pregnancies of which 31.6 per cent were multiple. Five per cent of all treatment cycles were complicated by mild, and 0.62 per cent by severe hyperstimulation. The factors involved in achieving a satisfactory pregnancy rate whilst avoiding complications are discussed. Most complications occurred during the first cycle in which the rise in oestrogen excretion suggested follicular development and human chorionic gonadotrophin (HCG) was given (the "first effective" treatment cycle). In such cycles the risk of hyperstimulation rose sharply when the day 6 urinary total estrogen level was above 150 mug. per 24 hours and the multiple pregnancy rate was increased by a large dose of HCG.

Topics: Abortion, Spontaneous; Adult; Amenorrhea; Chorionic Gonadotropin; Congenital Abnormalities; Estrogens; Female; Follicle Stimulating Hormone; Hernia, Umbilical; Humans; Infertility, Female; Luteinizing Hormone; Meningocele; Menotropins; Menstruation Disturbances; Pierre Robin Syndrome; Polycystic Ovary Syndrome; Pregnancy; Pregnancy, Multiple

Eight hMG-hCG therapy cycles in 6 anovulatory infertile patients are presented. Daily plasma estrogen monitoring during the therapy contributed to success in inducing ovulation in all 6, 3 of whom established pregnancies and delivered healthy babies. The duration of hMG therapy required varies among individuals. Duration and dosage can be determined on the basis of daily plasma estrogen levels. Administration hCG is recommended to trigger ovulation when these levels reach 300 to 600 pg/ml. Although success in ovulation induction and pregnancy is achievable, multiple ovulation and multiple pregnancy cannot be predicted or prevented.

Topics: Adult; Amenorrhea; Chorionic Gonadotropin; Clomiphene; Estrogens; Female; Follicle Stimulating Hormone; Humans; Hypogonadism; Infertility, Female; Luteinizing Hormone; Menotropins; Ovulation; Ovulation Detection; Polycystic Ovary Syndrome; Pregnancy; Pregnancy, Multiple; Progesterone

Topics: Adult; Amenorrhea; Chorionic Gonadotropin; Clomiphene; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Infertility, Female; Injections, Intramuscular; Luteinizing Hormone; Menotropins; Ovulation; Pituitary Gland; Polycystic Ovary Syndrome; Pregnancy

Topics: Amenorrhea; Clomiphene; Female; Humans; Lactation Disorders; Menotropins; Ovary; Ovulation; Polycystic Ovary Syndrome; Pregnancy

Topics: Adult; Amenorrhea; Body Temperature; Clomiphene; Contraceptives, Oral; Female; Fertilization; Follicle Stimulating Hormone; Hirsutism; Humans; Hypothalamus; Infertility, Female; Lactation Disorders; Luteinizing Hormone; Menotropins; Ovulation; Polycystic Ovary Syndrome; Pregnancy; Prognosis; Radioimmunoassay

Topics: Amenorrhea; Female; Fertilization; Humans; Infertility, Female; Menotropins; Ovulation; Polycystic Ovary Syndrome; Pregnancy; Pregnancy, Multiple; Retrospective Studies

Topics: Adolescent; Adult; Amenorrhea; Body Temperature; Dose-Response Relationship, Drug; Drug Interactions; Female; Follicle Stimulating Hormone; Gonadotropins, Pituitary; Humans; Hypopituitarism; Luteinizing Hormone; Menotropins; Ovarian Follicle; Ovulation; Polycystic Ovary Syndrome