menotropins and Ovarian-Hyperstimulation-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

To determine the relative efficacy of recombinant FSH (rFSH) and urinary FSH (uFSH) for ovarian stimulation in assisted reproductive techniques (ART).. Systematic review and meta-analysis of randomized, controlled trials comparing rFSH and uFSH.. Infertility centers providing treatment with ART.. Patients undergoing IVF with or without ICSI.. Controlled ovarian stimulation using uFSH or rFSH (follitropin alpha or follitropin beta).. Primary: rate of clinical pregnancy per cycle. Secondary: rates of spontaneous abortion, multiple pregnancy, and severe ovarian hyperstimulation syndrome (OHSS); total gonadotropin dose; serum E(2) level and number of follicles at hCG administration; number of oocytes retrieved.. Eighteen trials were included in the meta-analysis. Subgroup analyses demonstrated higher pregnancy rates with both follitropins compared with uFSH. However, statistical significance was reached only in the follitropin alpha versus uFSH comparison in IVF cycles, with an additional pregnancy for every 19 patients treated. Fewer units of rFSH than uFSH achieved the same E(2) level and oocyte yield. No differences were found between treatments in rates of spontaneous abortion, OHSS, and multiple gestation.. rFSH produced higher pregnancy rates per cycle than uFSH when follitropin alpha was used in IVF, and the total gonadotropin dose required was lower.

Topics: Abortion, Spontaneous; Estradiol; Female; Fertilization in Vitro; Follicle Stimulating Hormone; Humans; Menotropins; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pregnancy; Pregnancy, Multiple; Randomized Controlled Trials as Topic; Recombinant Proteins; Reproductive Techniques, Assisted; Sperm Injections, Intracytoplasmic; Treatment Outcome

We report a case of activated protein C (APC) resistance and deep calf vein thrombosis under controlled ovarian stimulation for in vitro fertilization. The thrombosis occurred before administration of human chorionic gonadotrophin for ovulation induction on the 8th day of hMG (human menopausal gonadotrophin). The patient was stimulated according to the long luteal protocol. Cases of arterial and venous thrombosis as a result of ovarian stimulations are reviewed.

Topics: Activated Protein C Resistance; Adult; Factor V; Female; Genetic Carrier Screening; Humans; Infertility, Female; Menotropins; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Point Mutation; Risk Factors; Thrombophlebitis

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

Thromboembolism as a complication of hormonal ovarian stimulation in the context of artificial reproductive techniques is rare and seems to occur when OHS is present. Although accompanied by high serum estrogen concentrations, hCG seems to play a central role in the development of OHS, which has been observed in women with 17,18-desmolase deficiency who have low estrogen levels after induction of ovulation with hGC. Although there is some evidence that hormonal ovarian stimulation with HMG, leading to elevated estrogen levels, and ovulation induction with hCG in preparation for in vitro fertilization are associated with a state of hypercoagulability, the exact role of estrogens, hCG and the physicochemical changes (fluid shift into third spaces) involved in OHS remain to be elucidated.

Topics: Chorionic Gonadotropin; Female; Gonadal Steroid Hormones; Humans; Menotropins; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Reproductive Techniques; Thromboembolism; Thrombophilia

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

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

Topics: Female; Humans; Menotropins; Ovarian Hyperstimulation Syndrome; Pregnancy; Pregnancy Outcome; Risk Factors

Although the use of luteinizing hormone-releasing hormone (LHRH) agonists and human menopausal gonadotropin (hMG) for ovarian stimulation in assisted reproduction has gained widespread popularity, a number of major issues regarding their use remain unresolved. Some of these issues are examined in the light of recent developments. The routine use of LHRH agonists produces significantly higher pregnancy and livebirth rates compared with conventional methods of ovarian stimulation. A number of prospective, randomized studies have shown that the long protocol of LHRH agonist administration is superior to the short and ultrashort protocols, and it appears that early follicular phase initiation of the long protocol may be particularly beneficial. Another major advantage of the long protocol of LHRH agonist administration is that, with its use, precise timing of human chorionic gonadotropin (hCG) administration is not important. It would, therefore, appear that the routine use of LHRH agonists has both medical as well as practical advantages.

Topics: Abortion, Spontaneous; Clinical Protocols; Drug Administration Schedule; Drug Therapy, Combination; Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Menotropins; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pregnancy; Pregnancy Outcome; Prospective Studies; Randomized Controlled Trials as Topic; Time Factors

The use of purified FSH versus classical hMG for normo-ovulatory women superovulation in an IVF programme could reduce the spontaneous LH surges incidence and/or increase the numbers of retrieved oocytes and transfers. In poor responders the advantage of high FSH doses is very discussed. Because of possible adverse effects of LH excess, high responders remain theoretically the best indication. Nevertheless only few prospective studies showed a significant reduction of multiple pregnancies and hyperstimulations by pure FSH. Most effective seems to be using low gonadotropins doses.

Topics: Adult; Clinical Trials as Topic; Female; Fertilization in Vitro; Follicle Stimulating Hormone; Humans; Infertility, Female; Luteinizing Hormone; Menotropins; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pregnancy; Pregnancy, Multiple; Prospective Studies

Induction of ovulation has its own risks. Since this treatment is elective the physician should be convinced that it is really indicated for the specific patient. Multiple pregnancies still occur in 4 to 15% in in vivo treatment and in 15 to 20% in assisted reproduction. Abortions occur in 20% of the pregnancies achieved. These numbers demonstrate the complexity of induction of ovulation. In recent years the average age of the treated patient has increased, but it is too early to see whether this influences the frequency of complications. The physician should be aware of the possible complications and should remain in contact with the patients at risk after completion of the treatment. The patient should be well informed about the possible complications before starting treatment. At the end of the treatment she should be able to recognize any clinical warning signs of OHSS and inform her physician, in order to be treated appropriately. Further studies of the pathogenesis of OHSS in the future will hopefully lead to more specific treatments or even prevention of this phenomenon. The increasing experience in selective fetal reduction seems to be a practical solution to high rank multifetal gestation, preventing extreme prematurity and its sequelae.

Topics: Female; Fertilization in Vitro; Follicular Cyst; Gonadotropin-Releasing Hormone; Humans; Menotropins; Ovarian Cysts; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pregnancy; Pregnancy, Multiple; Risk Factors

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

Ovulation is the result of a perfectly balanced and coordinated function of endocrine, paracrine, and autocrine systems. Any disruption in the delicately coordinated interaction between the integrated components of the hypothalamic-pituitary-ovarian axis may lead to ovulatory dysfunction, a multifactorial entity. The widening scope of knowledge regarding physiology of the reproductive processes as well as rapid development of new diagnostic methods and therapeutic procedures necessitates the continued reassessment and identification of factors leading to ovulatory dysfunction and the design of safe therapy for this condition. The combined use of serial ultrasonography and estradiol measurements should be the standard method of ovulation induction monitoring. The identification of high-risk groups prior to the initiation of ovulation induction regimens must also be taken into consideration if we want to improve pregnancy rate and reduce the incidence of hyperstimulation to a minimal level.

Topics: Abnormalities, Drug-Induced; Chorionic Gonadotropin; Female; Humans; Infertility, Female; Menotropins; Ovarian Hyperstimulation Syndrome; Ovulation; Ovulation Induction

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

To evaluate the efficacy and safety of highly purified human menotropin (HP-hMG) and recombinant follicle-stimulating hormone (rFSH) for controlled ovarian stimulation in a population of patients predicted to be high responders.. Randomized, open-label, assessor-blinded, parallel-group, noninferiority trial.. Fertility centers.. A total of 620 women with serum antimüllerian hormone (AMH) ≥5 ng/mL.. Controlled ovarian stimulation with HP-hMG or rFSH in a GnRH antagonist assisted reproductive technology (ART) cycle. Fresh transfer of a single blastocyst was performed unless ovarian response was excessive, in which all embryos were cryopreserved. Subjects could undergo subsequent frozen blastocyst transfer within 6 months of randomization.. Ongoing pregnancy rate (OPR) after fresh transfer (primary endpoint), as well as cumulative live birth, ovarian hyperstimulation syndrome (OHSS), and pregnancy loss rates.. OPR/cycle start after fresh transfer was 35.5% with HP-hMG and 30.7% with rFSH (difference: 4.7%, 95% CI -2.7%, 12.1%); noninferiority was established. Compared to rFSH, HP-hMG was associated with significantly lower OHSS (21.4% vs. 9.7% respectively; difference: -11.7%, 95% CI -17.3%, -6.1%) and cumulative early pregnancy loss rates (25.5% vs. 14.5% respectively; difference: -11.0%, 95% CI -18.8%, -3.14%). Despite 43 more transfers in the rFSH group, cumulative live birth rates were similar with HP-hMG and rFSH at 50.6% and 51.5% respectively (difference: -0.8%, 95% CI -8.7%, 7.1%).. In high responders, HP-hMG provided comparable efficacy to rFSH with fewer adverse events, including pregnancy loss, suggesting its optimized risk/benefit profile in this population.. NCT02554279 (clinicaltrials.gov).

Topics: Abortion, Spontaneous; Adult; Anti-Mullerian Hormone; Biomarkers; Female; Fertility; Fertility Agents, Female; Follicle Stimulating Hormone, Human; Humans; Infertility; Live Birth; Male; Menotropins; Ovarian Hyperstimulation Syndrome; Ovary; Ovulation; Ovulation Induction; Pregnancy; Pregnancy Rate; Prospective Studies; Recombinant Proteins; Single Embryo Transfer; Sperm Injections, Intracytoplasmic; Treatment Outcome; United States; Young Adult

Women with high-AMH levels have an increased risk of ovarian hyperstimulation syndrome (OHSS). Studies have suggested that highly purified menotropin (HP-hMG) Menopur® reduces the risk. We, therefore, studied use of low-dose (112.5 IU/day) HP-hMG in ovulatory and anovulatory patients with high AMH (>32 pmol/L). The primary endpoint was the distribution of patients with appropriate, excessive, and inadequate response (5-14, ≥15, and ≤4 oocytes). Another endpoint was frequency of OHSS. Totally 115 women were included and 78 (67.8%) had an appropriate, 8 (7.0%) an excessive, and 29 (25.2%) an inadequate response. The number of oocytes was independent on AMH levels and ovulatory status but declined significantly with increasing bodyweight (R

Topics: Adult; Anovulation; Anti-Mullerian Hormone; Dose-Response Relationship, Drug; Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Menotropins; Ovarian Hyperstimulation Syndrome; Ovulation; Ovulation Induction; Pregnancy; Pregnancy Rate

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

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

The aim was to compare ovarian response and clinical outcome of potential high-responders after stimulation with highly purified menotropin (HP-hMG) or recombinant follicle-stimulating hormone (rFSH) for in vitro fertilisation/intracytoplasmic sperm injection. Retrospective analysis was performed on data collected in two randomized controlled trials, one conducted following a long GnRH agonist protocol and the other with an antagonist protocol. Potential high-responders (n = 155 and n = 188 in the agonist and antagonist protocol, respectively) were defined as having an initial anti-Müllerian hormone (AMH) value >75th percentile (5.2 ng/ml). In both protocols, HP-hMG stimulation in women in the high AMH category was associated with a significantly lower occurrence of high response (≥15 oocytes retrieved) than rFSH stimulation; 33% versus 51% (p = 0.025) and 31% versus 49% (p = 0.015) in the long agonist and antagonist protocol, respectively. In the potential high-responder women, trends for improved live birth rate were observed with HP-hMG compared with rFSH (long agonist protocol: 33% versus 20%, p = 0.074; antagonist protocol: 34% versus 23%, p = 0.075; overall population: 34% versus 22%, p = 0.012). In conclusion, the type of gonadotropin used for ovarian stimulation influences high-response rates and potentially clinical outcome in women identified as potential high-responders.

Topics: Adult; Anti-Mullerian Hormone; Biomarkers; Embryo Transfer; Female; Fertility Agents, Female; Fertilization in Vitro; Follicle Stimulating Hormone, Human; Gonadotropin-Releasing Hormone; Humans; Infertility, Female; Live Birth; Menotropins; Ovarian Hyperstimulation Syndrome; Ovary; Ovulation Induction; Pregnancy; Recombinant Proteins; Retrospective Studies; Risk; Sperm Injections, Intracytoplasmic; Up-Regulation

In this prospective, follow-up study of 102 high-risk oocyte donors in their luteal phase, we found a complete absence of ovarian hyperstimulation syndrome (no signs of hemoconcentration or ascites) after the donors were triggered with a gonadotropin releasing-hormone (GnRH) agonist. Due to its powerful preventive effect, the GnRH antagonist protocol combined with a GnRH agonist trigger should preferentially be used in egg donors; in conjunction with an effective luteal support or embryo cryopreservation, the protocol could also be applied to high-risk in vitro fertilization patients.

Topics: Adolescent; Adult; Female; Follicle Stimulating Hormone; Follow-Up Studies; Gonadotropin-Releasing Hormone; Humans; Luteal Phase; Menotropins; Oocyte Donation; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Recombinant Proteins; Risk Factors; Time Factors; Tissue Donors; Young Adult

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

To help inform healthcare treatment practices and funding decisions, an economic evaluation was conducted to compare the two leading gonadotrophins used for IVF in Belgium. Based on the results of a recently published meta-analysis, a simulated decision tree model was constructed with four states: (i) fresh cycle, (ii) cryopreserved cycle, (iii) live birth and (iv) treatment withdrawal. Gonadotrophin costs were based on highly purified human menopausal gonadotrophin (HP-HMG; Menopur) and recombinant FSH (rFSH) alpha (Gonal-F). After one fresh and one cryopreserved cycle the average treatment cost with HP-HMG was lower than with rFSH (HP-HMG euro3635; rFSH euro4103). The average cost saving per person started on HP-HMG when compared with rFSH was euro468. Additionally, the average costs per live birth of HP-HMG and rFSH were found to be significantly different: HP-HMG euro9996; rFSH euro13,009 (P < 0.0001). HP-HMG remained cost-saving even after key parameters in the model were varied in the probabilistic sensitivity analysis. Treatment with HP-HMG was found to be the dominant treatment strategy in IVF because of improved live birth rates and lower costs. Within a fixed healthcare budget, the cost-savings achieved using HP-HMG would allow for the delivery of additional IVF cycles.

Topics: Cost-Benefit Analysis; Cryopreservation; Economics, Medical; Female; Follicle Stimulating Hormone; Humans; Live Birth; Menotropins; Ovarian Hyperstimulation Syndrome; Pregnancy; Probability; Recombinant Proteins; Reproductive Techniques, Assisted; Sensitivity and Specificity; Treatment Outcome

This pilot study was conducted to compare the results of intrauterine insemination (IUI) under ovarian stimulation with either letrozole (Femara) or human menopausal gonadotrophin (HMG). A randomized controlled trial was conducted. Eighty women aged 20-35 years with unexplained infertility of at least 2 years' duration were randomized according to a computer-generated randomization list into the letrozole group and the HMG group. Letrozole was administered at 5 mg/day from day 3 to day 7 of the IUI cycle. HMG injections were started on day 3 at a dose of 75 IU for women under 30 years old and 150 IU for women over 30 years old and monitored periodically by vaginal ultrasound and oestradiol concentrations. The variables selected for analysis were clinical pregnancy rate, endometrial thickness, length of follicular phase and number of preovulatory follicles. No statistically significant difference in clinical pregnancy rates per cycle was found for patients in the letrozole or HMG group (18.4 versus 15.7%). Cost was significantly higher in the HMG stimulation cases (P < 0.001) and no injections were required in the letrozole group. In conclusion, letrozole offers a new treatment regimen in ovarian stimulation regimens for IUI that is cost effective, simple and convenient for the patients.

Topics: Adult; Aromatase Inhibitors; Endometrium; Female; Follicular Phase; Humans; Infertility, Female; Insemination, Artificial, Homologous; Letrozole; Luteinization; Male; Menotropins; Nitriles; Ovarian Hyperstimulation Syndrome; Pilot Projects; Pregnancy; Pregnancy Rate; Triazoles

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

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

This prospective, double-blind, randomized, multicentre study compared the efficacy and safety of recombinant human follicle stimulating hormone (r-hFSH; Gonal-F((R))) versus highly purified urinary FSH (u-hFSH HP; Metrodin((R)) HP) in women undergoing ovarian stimulation for in-vitro fertilization, including intracytoplasmic sperm injection. A total of 278 patients began a long gonadotrophin-releasing hormone agonist protocol, then 139 received r-hFSH and 139 u-hFSH HP, 150 IU/day administered s.c., for the first 6 days of treatment. On day 7, the dose was adjusted, if necessary, according to ovarian response. Human chorionic gonadotrophin (HCG, 10 000 IU, s.c.) was administered once there was more than one follicle 18 mm in diameter and two others >/=16 mm. Oocyte retrieval was performed 36-38 h after HCG injection: 128 patients (92%) receiving r-hFSH and 113 (81%) receiving u-hFSH HP had at least one oocyte retrieved. Among patients receiving r-hFSH, there was a significantly higher mean (+/- SD) number of oocytes retrieved (11.0 +/- 5.9 versus 8.8 +/- 4.8 with u-hFSH HP; P = 0. 002) and mean number of embryos obtained (5.1 +/- 3.7 versus 3.5 +/- 2.9 with u-hFSH HP; P = 0.0001). With r-hFSH, significantly fewer FSH treatment days (11.7 +/- 1.9 versus 14.5 +/- 3.3) and 75 IU ampoules (27.6 +/- 10.2 versus 40.7 +/- 13.6) were required than with u-hFSH HP (P = 0.0001). Embryo replacement on day 2-3 after oocyte retrieval resulted in 36 liveborn children in the Gonal-F((R)) group and 33 in the Metrodin HP((R)) group (not significant). There were seven cases (5.0%) of ovarian hyperstimulation syndrome in the r-hFSH group and three (2.2%), in the u-hFSH HP group (not significant). It is concluded that r-hFSH is more effective than u-hFSH in inducing multiple follicular development.

Topics: Adolescent; Adult; Double-Blind Method; Embryo, Mammalian; Female; Fertilization in Vitro; Follicle Stimulating Hormone; Follicle Stimulating Hormone, Human; Humans; Luteinizing Hormone; Menotropins; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pregnancy; Pregnancy Rate; Recombinant Proteins; Sperm Injections, Intracytoplasmic

A total of 346 women with normal ovulatory function was stimulated with human menopausal gonadotrophins (HMG) to attain ovarian stimulation for IVF or intracytoplasmic sperm injection (ICSI). Stimulation with HMG started on cycle day 2 or 3. After 6 days of stimulation, Cetrorelix in its minimum effective multiple dose of 0. 25 mg/day, was administered daily until induction of ovulation. In total, 333 patients (96.2%) reached the day of HCG administration, and 324 (93.6%) underwent oocyte retrieval. A mean of 25.2 ampoules of HMG was applied for a mean of 10.4 days. Cetrorelix was administered for a mean time lapse of 5.7 days. The mean normal fertilization rate was 60% in the IVF group and 59% in the ICSI group. Seventy pregnancies were attained, reflecting an ongoing clinical pregnancy rate of 24% per transfer. The ongoing clinical implantation rate was 11.4%. Only three cases of raised luteinizing hormone (LH) (>/=10 IU/l) with increased progesterone secretion (>/=1 ng/ml) were observed after initiation of Cetrorelix administration, reflecting an incidence of premature luteinization of 0.9%. The abortion rate was 17%. The incidence of severe ovarian hyperstimulation syndrome (World Health Organization grade III) was as low as 0.6%.

Topics: Dose-Response Relationship, Drug; Embryo, Mammalian; Female; Fertilization in Vitro; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Luteinizing Hormone; Menotropins; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pregnancy; Pregnancy Rate; Prospective Studies

Topics: Adult; Chorionic Gonadotropin; Estradiol; Female; Fertilization; Fertilization in Vitro; Humans; Maternal Age; Menotropins; Menstruation; Ovarian Hyperstimulation Syndrome; Ovary; Ovulation Induction; Pregnancy Rate; Risk Factors; Sperm Injections, Intracytoplasmic

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

Thirty women undergoing in-vitro fertilization or intracytoplasmic sperm injection considered to be at high risk of ovarian hyperstimulation syndrome (OHSS) were randomly allocated to have early unilateral follicular aspiration (EUFA) (group 1) or coasting (group 2) when the serum oestradiol concentration was >6000 pg/ml and there were more than 15 follicles each of >/=18 mm diameter in each ovary. EUFA was performed in group 1 at 10-12 h after the human chorionic gonadotrophin (HCG) trigger injection and human menopausal gonadotrophin (HMG) were withheld for 4.9 +/- 1.6 days until serum oestradiol concentrations fell below 3000 pg/ml when HCG was administered. The mean total dose and duration of administration of HMG were similar in groups 1 and 2 (48.3 +/- 17.4 and 50.2 +/- 16.5 ampoules; 13.7 +/- 2.2 and 14.1 +/- 3.2 days respectively). The mean serum oestradiol concentrations (9911 pg/ml versus 10 055 pg/ml) and number of follicles (43.3 versus 41.4) seen in both ovaries on the day of HCG administration in group 1 and on the day coasting was commenced in group 2 were also similar. After coasting, the mean serum oestradiol concentration on the day of HCG administration in group 2 was lower than in group 1 (1410 pg/ml versus 9911 pg/ml; P < 0.001). The mean serum progesterone concentrations on the day of HCG administration in both groups were similar, and fell in all women in group 2. The mean number of oocytes retrieved and percentage of oocytes retrieved per follicle punctured was significantly higher in group 1 (15.4 +/- 2.1 versus 9.6 +/- 3.2, P < 0.001; 91.4 +/- 4.4% versus 28.3 +/- 3.7%, P < 0.001 respectively). The fertilization and embryo cleavage rates were similar in both groups. Clinical pregnancy was diagnosed in 6/15 (40%) patients in group 1 and in 5/15 (33%) patients in group 2, while four women in group 1 and three in group 2 developed severe OHSS.

Topics: Adult; Chorionic Gonadotropin; Embryo Transfer; Estradiol; Female; Fertilization in Vitro; Humans; Menotropins; Ovarian Follicle; Ovarian Hyperstimulation Syndrome; Pregnancy; Prospective Studies; Risk Factors; Suction; Time Factors

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

In vitro fertilization had been previously suggested by us as a means of "rescue" for patients with imminent ovarian hyperstimulation syndrome (OHSS) during treatment with human menopausal gonadotropin (hMG). We evaluated the pregnancy rate of rescued IVF cycles.. During the years 1994-1995, women treated with hMG and at risk of developing OHSS were referred to our IVF unit. Their estradiol level was above 1500 pg/ml, and eight or more follicles were observed by ultrasonography in all the patients. These high responders were offered the option to undergo ovum aspiration. We report the pregnancy rate in this group of patients.. Thirty-nine women were referred to our unit for rescue IVF. Two were uneligible due to high progesterone concentrations. Thirty-seven women underwent ovum pickup and 32 had embryo transfer. The clinical pregnancy rate was 40% (13/32). Only two women had clinical OHSS.. We suggest that rescue IVF may be considered in hMG cycles of high responders with imminent OHSS. Rescue IVF offers a high rate of conception, avoids high-order multiple pregnancy, and appears not to increase the risk of OHSS in these women.

Topics: Embryo Transfer; Female; Fertility Agents, Female; Fertilization in Vitro; Humans; Menotropins; Ovarian Hyperstimulation Syndrome; Pregnancy; Pregnancy Rate; Ultrasonography

To describe endometrial wavelike activity, endometrial thickness, and texture in controlled ovarian hyperstimulation (COH) cycles.. Prospective observational ultrasound study.. University hospital-based infertility clinic.. Thirty-five COH cycles in 19 women with unexplained infertility.. Transvaginal ultrasound examination was performed throughout COH cycles. Intrauterine insemination was performed after hCG administration.. Endometrial wavelike activity, wave frequency, wave velocity, endometrial thickness, and endometrial texture.. Endometrial wavelike activity increased from menstruation to ovulation and decreased in the luteal phase. On day hCG+2, endometrial wave-like activity was observed in all cycles. Waves from cervix to fundus prevailed in the periovulatory phase. Endometrial wavelike activity was related significantly to endometrial thickness at the start of ovarian stimulation and in the luteal phase. Endometrial thickness increased throughout the cycle. Endometrial texture showed periovulatory a triple-line aspect.. In COH cycles, endometrial wavelike activity is more pronounced than in spontaneous cycles. The number of follicles and endometrial wavelike activity were not correlated significantly. This is the first prospective study to provide longitudinal observational evidence that endometrial thickness increases throughout the COH cycle and that a triple line pattern develops.

Topics: Adult; Endometrium; Female; Humans; Infertility, Female; Menotropins; Ovarian Follicle; Ovarian Hyperstimulation Syndrome; Prospective Studies; Ultrasonography

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

Unilateral ovarian follicular aspiration 6-8 h prior to trigger administration of human chorionic gonadotrophin (HCG) was performed or not in 31 women at serious risk of ovarian hyperstimulation syndrome (OHSS) after ovarian stimulation for in-vitro fertilization (IVF)-embryo transfer or intracytoplasmic sperm injection (ICSI) in this prospective randomized study. Unilateral follicular aspiration was performed in 16 women (group 1) matched for age, indication for fertility treatment, and the amount and duration of gonadotrophin exposure with 15 women not receiving aspiration treatment (group 2). There was a statistically significantly (P < 0.001) lower mean number of oocytes obtained from group 1 women (14.9 +/- 1.8 vs 22.6 +/- 2.4). The fertilization (53.2 +/- 2.6 vs 65.5 +/- 1.35%) and embryonic cleavage (91.3 +/- 2.1 vs 90.2 +/- 1.75%) rates were similar in both groups. OHSS occurred in women from both groups (group 1: 25% vs group 2: 33.3%) being severe OHSS in two women from group 1 and one from group 2. We conclude that unilateral ovarian early follicular aspiration prior to HCG trigger administration does not reduce the occurrence of severe OHSS in women at risk.

Topics: Adult; Chorionic Gonadotropin; Estradiol; Female; Fertilization in Vitro; Humans; Menotropins; Ovarian Follicle; Ovarian Hyperstimulation Syndrome; Pregnancy; Prospective Studies; Suction

To compare the low-dose recombinant FSH and hMG protocols in treatment of patients with history of severe ovarian hyperstimulation syndrome (OHSS).. A prospective study on 22 patients with history of severe OHSS. Group A (n = 14) was treated with low-dose recombinant FSH 40 cycles and group B (n = 8) was treated with low-dose hMG in 26 cycles.. The Egyptian IVF-ET Center, Cairo, Egypt.. Twenty-two patients with a history of severe OHSS.. Ovulation induction.. Estradiol, number of follicles, number of hMG ampules, pregnancy rate (PR), and the development of OHSS.. The cancellation rate, mean E2 level on day of hCG, mean number of days of stimulation, and the mean number of ampules per cycle were 10%, 523 +/- 166 pg/mL (conversion factor to SI unit, 3.671), 17.8 +/- 5.4, and 19 +/- 6.5 in group A and 19.2%, 554 +/- 152 pg/mL, 14.6 +/- 2.5, and 16.1 +/- 3.6 in group B, respectively. Treatment resulted in eight pregnancies (20% per cycle) and two abortions (25%) in group A. In group B, four pregnancies resulted (15.4% per cycle) and two patients aborted (50%). No cases of OHSS developed in both groups. There were no significant differences in all parameters between the two groups.. Recombinant FSH low-dose protocol proved to be as effective as low-dose hMG in producing reasonable ovulation and PRS in polycystic ovary syndrome patients with a history of severe OHSS and the protocol was safe concerning the risk of development of OHSS.

Topics: Abortion, Spontaneous; Egypt; Embryo Transfer; Estradiol; Female; Fertilization in Vitro; Follicle Stimulating Hormone; Humans; Menotropins; Ovarian Hyperstimulation Syndrome; Pregnancy; Prospective Studies; Recombinant Proteins; Risk Factors

The purpose of the present study was (i) to assess the value of using a low dose of hMG (75 IU/day) to achieve ovarian stimulation in women who have previously shown an exaggerated response to a standard dose of 150 IU human menopausal gonadotropin/day in a desensitization (group I) or flare-up (group II) protocol and (ii) to determine whether the choice of GnRH-a regimen in a subsequent cycle, namely, a desensitization or flare-up protocol, influenced the effectiveness of the low dose of hMG.. In group I, 75% (12/16) and 57% (8/14) of the subsequent desensitization and flare-up protocols, respectively, were cancelled because of inadequate ovarian response. Similarly, the cancellation rates in group II were 10 of 10 and 7 of 11 (64%), respectively. The total cancellation rate (groups I and II together) with the desensitization protocol was higher than that using the flare-up protocol (P < 0.05).. The simple use of a reduced dose of hMG (75 IU/day) for subsequent in vitro fertilization in women to minimize the risk of the development of ovarian hyperstimulation is of limited benefit since a large proportion then shows an inadequate response. This is particularly pronounced with a subsequent desensitization protocol which does not utilize endogenous gonadotropins to initiate follicular development.

Topics: Adult; Buserelin; Dose-Response Relationship, Drug; Embryo Transfer; Estradiol; Female; Fertilization in Vitro; Gonadotropins; Humans; Leuprolide; Menotropins; Menstrual Cycle; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pregnancy; Pregnancy Outcome; Radioimmunoassay; Risk Factors

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 investigate the feasibility of IVF treatment with minimal monitoring during ovarian hyperstimulation.. Retrospective analysis and prospective study with real-time control group.. Transport IVF program with transport clinic and satellite clinics.. One hundred consecutive IVF cycles monitored at a transport clinic and 100 concurrent consecutive cycles monitored at satellite clinics, using the same stimulation-monitoring protocol and resulting in oocyte aspiration, are compared retrospectively for the number of ultrasound (US) measurements carried out during monitoring and for results of IVF treatment. No patient selection took place. After introduction of a minimal monitoring protocol at a transport clinic, a prospective study was started comparing 100 minimal monitoring cycles at a transport clinic with 100 concurrent conventional monitoring cycles at satellite clinics, all resulting in oocyte aspiration. Patients entered the retrospective or prospective study only once. In all cases the same laboratory facility was used. Monitoring of ovarian hyperstimulation was done with US measurements only. Cycles were canceled for impending ovarian hyperstimulation syndrome (OHSS) when > 35 follicles were seen to develop during hyperstimulation.. Retrospective analysis shows no difference for the average number of US measurements at transport and satellite clinics (2.8 +/- 0.9 and 3.0 +/- 1.0; mean +/- SD). No differences were found in the number of ongoing pregnancies obtained in the two groups: 22 and 18, respectively. One case of severe OHSS occurred in the satellite clinic group. Introduction of minimal monitoring at the transport clinic gives a significant reduction of the average number of US measurements at the transport clinic compared with satellite clinics, where conventional monitoring continued to be used (1.5 +/- 0.8 versus 2.8 +/- 0.9). Ongoing pregnancies at transport and satellite clinics numbered 33 and 26, respectively. In both groups one patient developed severe OHSS. Sixty-two percent of cycles at the transport clinic were monitored with one US measurement only. No cancellations for impending OHSS occurred during the study period.. A large group of patients need only one US measurement during monitoring of ovarian hyperstimulation. Minimal monitoring gives a useful further simplification of the clinical phase of IVF treatment, without adverse effects on treatment outcome and incidence of OHSS.

Topics: Ambulatory Care Facilities; Female; Fertilization in Vitro; Humans; Menotropins; Ovarian Hyperstimulation Syndrome; Ovary; Ovulation Induction; Pregnancy; Prospective Studies; Retrospective Studies; Ultrasonography

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

We studied the peri-ovulatory and luteal phases in 38 human menopausal gonadotrophin (HMG)-stimulated cycles, in which ovulation was triggered with four different i.v. bolus ovulation triggers: 100 micrograms gonadotrophin-releasing hormone (GnRH; group A, n = 9), 500 micrograms GnRH agonist (GnRHa; group B, n = 10), 10,000 IU human chorionic gonadotrophin (HCG; group C, n = 10) and 500 micrograms GnRH (group D, n = 9). Endogenous luteinizing hormone (LH) surges occurred in all cycles of groups A, B and D. The rise was slowest but highest in group B (P < 0.0001) and lowest in group A. Although the t0 serum oestradiol values were similar in all groups, day +8 oestradiol and day +4 and +8 progesterone concentrations were higher in group C (P < 0.05). At day +4 and +8, serum LH concentrations were lowest (P < 0.01) but follicle stimulating hormone (FSH) concentrations were higher. Clinically, day +8 luteal scores showed a more conspicuous degree of ovarian hyperstimulation in the HCG group (P = 0.0292). Luteal insufficiency, defined as cycles with progesterone concentrations of < 8 ng/ml, occurred much more frequently in groups A, B and D than in group C (day +4: P < 0.0003; day +8: P < 0.0001), despite progesterone supplementation. Three pregnancies (one in group C and two in group D) and one moderate case of ovarian hyperstimulation syndrome (OHSS) (in a non-conceptional group D cycle) occurred. These findings show that (i) ovulation occurs and pregnancy can be achieved following an endogenous LH surge induced by GnRH and its agonists, (ii) a high frequency of luteal insufficiency occurs in such cycles even with luteal supplementation and (iii) OHSS cannot be totally prevented by this approach, although cycles with an endogenous LH surge in general result in fewer subclinical signs of ovarian hyperstimulation.

Topics: Buserelin; Chorionic Gonadotropin; Corpus Luteum Maintenance; Estradiol; Female; Follicle Stimulating Hormone; Humans; Infertility, Female; Injections, Intravenous; Luteal Phase; Luteinizing Hormone; Menotropins; Ovarian Hyperstimulation Syndrome; Ovulation; Ovulation Induction; Pregnancy; Progesterone

A total of 114 patients admitted to an in-vitro fertilization-embryo transfer programme for the first time, were randomly assigned to the study group or controls. Gonadotrophin-releasing hormone analogue (GnRHa) and human menopausal gonadotrophin (HMG) were used for ovulation induction. The study patients were followed up merely by ultrasonography and the controls by ultrasonography and serum determinations of oestradiol, progesterone and luteinizing hormone (LH). There was no significant difference in the duration and total amount of HMG used for ovulation induction (10.9 versus 11.5 days and 34.8 versus 37.9 ampoules, respectively). The number of oocytes retrieved (11.7 versus 13.4) and the numbers of embryos replaced (2.6 versus 2.8) and cryopreserved (1.9 versus 3.3) were also similar. Pregnancy rates were similar. Pregnancy rate per ovum retrieval was 22.2 versus 25% and per embryo transfer 27.2 versus 26.5%. Oestradiol patterns were also similar. The rate and severity of ovarian hyperstimulation syndrome were virtually identical. We conclude that 'ultrasound-only' monitoring of ovulation induction in IVF cycles treated by GnRHa-HMG in the long protocol is as effective and safe as the conventional ultrasound and hormone determination, but far simpler, swifter and more cost-effective.

Topics: Adult; Embryo Transfer; Estradiol; Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Humans; Luteinizing Hormone; Menotropins; Ovarian Follicle; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Progesterone; Ultrasonography

Fertile Yoruba women from western Nigeria have a much higher incidence of naturally conceived multizygotic twin and triplet pregnancies than Caucasians. The objective of the present study was to determine whether there are differences between infertile Yoruba and Caucasian women in terms of ovarian response in stimulate cycles for assisted conception. A total of 11 Yoruba women were scheduled for 14 in-vitro fertilization (IVF) and one gamete intra-Fallopian transfer (GIFT) cycles from 1990 to 1992. The Caucasian group consisted of 209 women scheduled for 213 IVF and 22 GIFT cycles during the same period. Buserelin, 500 micrograms subcutaneously daily, was started in the mid-luteal phase to achieve pituitary desensitization. Ovarian stimulation was with variable amounts of menopausal gonadotrophins. Human chorionic gonadotrophin (HCG) was given to trigger the ovulatory process. The Yoruba and Caucasian groups were similar in age and body weight, but significantly more Yorubas (45 versus 11%; P < 0.005) had ultrasound features of polycystic ovary syndrome (PCOS). The serum oestradiol concentration (3024 versus 2058 pg/ml; P < 0.05) and number of follicles > 14 mm in diameter (15.5 versus 9.5; P < 0.05) on the day of HCG were higher in the Yoruba group. The ovarian hyperstimulation syndrome (OHSS) was also more prevalent in the Yoruba group (20 versus 5%; P < 0.05). No difference was found in clinical pregnancy or embryo implantation rates. These results show a higher tendency toward exaggerated ovarian response in infertile Yoruba than Caucasian women, associated with a higher prevalence of PCOS. The risk of developing symptomatic OHSS is higher in Yoruba women.

Topics: Embryo Implantation; Estradiol; Female; Fertilization in Vitro; Gamete Intrafallopian Transfer; Humans; Incidence; Menotropins; Nigeria; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pregnancy; Pregnancy, Multiple

Three long protocols of ovarian stimulation for IVF using long acting GnRH agonist and hMG were compared. 3 molecules were used: Triptoreline (Décapeptyl* 3.75 mg), gosereline (Zoladex*) and leuproreline (Enantone* 3.75 mg). Assigning of these 3 protocols were randomised. 63, 68 and 67 cycles of stimulation were studied. Results in term of pregnancy are the same in the 3 groups. Only a tendency of lower frequency of ovarian hyperstimulation in Décapeptyl 3.75 mg group is found, associated with less embryo and less cycles with cryopreservation of supernumeraries embryos (p = 0.1).

Topics: Adult; Clinical Protocols; Delayed-Action Preparations; Drug Therapy, Combination; Female; Fertilization in Vitro; Goserelin; Humans; Leuprolide; Menotropins; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pregnancy; Pregnancy Outcome; Triptorelin Pamoate

In multicenter studies involving 3002 courses of human menopausal gonadotropins (hMG) therapy in 1286 patients, 20% of the patients who delivered had multiple gestations; 75% of these were twins and 25% were triplets or higher parity. Our stimulation regimen is very conservative in that we 1) try to allow a female with LPD and regular cycles but not reaching a mature follicle to first select her dominant follicle and wait until the serum E2 reaches approximately 100 pg/mL then add the hMG. With anovulatory women we frequently begin with only 75 IU hMG and gradually increase the hMG dosage. Using this approach we have usually attained at least a 70% pregnancy rate in six months. A study was performed to see if this conservative approach resulted in a decreased multiple birth rate percentage especially with triplets or more. The study was to evaluate the outcome of 241 consecutive pregnancies in which hMG was the sole therapy. There were 203 with one gestation and 38 with multiples. Twins--32; triplets--6. Thus 15% (38/241) had multiple births; six of 38 (15%) of the multiples had triplets or more. Though our multiple birth rate and especially higher parity rate appears to be lower than average no statistical difference was found. Thus even with conservative use of hMG multiple births cannot be easily avoided.

Topics: Estradiol; Female; Humans; Luteinizing Hormone; Menotropins; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pregnancy; Pregnancy, Multiple; Progesterone; Prospective Studies; Ultrasonography, Prenatal

A total of 24 women with primary or secondary infertility due to oligo- or anovulation, were treated with human menopausal gonadotrophin (HMG). In 48 cycles, we used a gonadotrophin-releasing hormone agonist (GnRHa) nasal spray (buserelin) to induce a pre-ovulatory endogenous luteinizing hormone (LH) surge. In 44 cycles, there was a rapid rise of the serum LH concentration within 8 h from the first administration of GnRHa. One patient with pituitary hypogonadotrophic amenorrhoea showed a weak or no response in four treatment cycles. Conception occurred in 10 cycles (pregnancy/cycle (P/C) index = 22.7%), four of which ended in a spontaneous abortion and six of which are ongoing pregnancies. In 27 cycles, there was an increased risk for ovarian hyperstimulation syndrome (OHSS), defined as more than three follicles > or = 18 mm in diameter and/or serum oestradiol > 1200 pg/ml. Three of these treatment cycles gave rise to the development of moderate OHSS in the absence of exogenously administered human chorionic gonadotrophin, two being conception cycles.

Topics: Administration, Intranasal; Adult; Buserelin; Female; Humans; Luteinizing Hormone; Menotropins; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Receptors, LHRH; Risk Factors; Secretory Rate

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 determine if the administration of glucocorticoids reduced the rate of ovarian hyperstimulation syndrome (OHSS) in high-risk patients after ovarian stimulation for in vitro fertilization (IVF).. Prospective randomized study.. Thirty-one patients who were stimulated with human menopausal gonadotropin (hMG) after pituitary desensitization by gonadotropin-releasing hormone agonist and who developed greater than 20 follicles greater than 12 mm and/or had a serum estradiol (E2) level of greater than 10,000 pmol/L on the day of administration of human chorionic gonadotropin (hCG).. Patients were randomly divided into two groups. Those who were randomized to receive glucocorticoids (group A) (n = 17) were administered intravenous hydrocortisone, 100 mg, immediately after ultrasound (US)-directed oocyte recovery. Prednisolone, 10 mg three times per day, was given for 5 days starting on the day of oocyte recovery followed by prednisolone 10 mg two times a day for 3 days and 10 mg/d for 2 days. Those in group B (n = 14) did not receive any glucocorticoid treatment. In both groups, luteal support was provided by intramuscular injections of gestone 100 mg/d.. The two groups of patients were comparable in terms of age, duration of infertility, and total dose of hMG used. All had polycystic ovaries on US examination. On the day of hCG administration, the mean number of follicles in the two groups were 26.76 +/- 2.49 and 25.93 +/- 1.44 and the serum E2 concentration 13,404 +/- 710 and 13,915 +/- 901 pmol/L, respectively. There were no significant differences in the number of oocytes collected or in the fertilization, cleavage, and implantation rates in the two groups. The pregnancy rates per initiated cycle were 41.18% and 35.71%, respectively. Seven of the 17 patients (41.2%) who received glucocorticoids developed ovarian hyperstimulation syndrome compared with 6 of the 14 patients (42.9%) who did not receive glucocorticoids.. Administrations of glucocorticoids to high risk patients did not reduce the rate of OHSS after ovarian stimulation for IVF.

Topics: Adult; Chorionic Gonadotropin; Embryo Transfer; Estradiol; Female; Fertilization in Vitro; Glucocorticoids; Humans; Hydrocortisone; Menotropins; Ovarian Follicle; Ovarian Hyperstimulation Syndrome; Prednisolone; Pregnancy; Prospective Studies

The role of luteinizing hormone (LH) in controlled ovarian hyperstimulation (COH) requires more evidence for its efficacy. Several studies compared recombinant human LH (r-hLH) or human menopausal gonadotropin (hMG) in combination with recombinant human follicle-stimulating hormone (r-hFSH) but lack the results with GnRH-antagonist protocol and in Asians.. With a total of 503 cycles, the results revealed that the r-hFSH+r-hLH group performed better in terms of numbers of oocytes retrieved (r-hFSH+hMG vs. r-hFSH+r-hLH, 11.7 vs. 13.7, p=0.014), mature oocytes (8.7 vs. 10.9, p=0.001), and fertilized oocytes (8.3 vs. 9.8, p=0.022), while other outcomes were comparable. The analysis of first ET cycles also showed similar trends. Although the implantation rate (39% vs. 43%, p=0.37), pregnancy rate (52% vs. 53%, p=0.90), and live birth rate (39% vs. 45%, p=0.19) were not significantly different, the miscarriage rate was higher in the r-hFSH+hMG group than the r-hFSH+r-hLH group (26% vs. 15%, p<0.05) in first ET cycles. The cumulative pregnancy rate was significantly higher in the r-hFSH+r-hLH group (53% vs. 64%, p=0.02). No significant difference in rates of ovarian hyperstimulation syndrome (OHSS) was observed.. The results support the hypothesis that the treatment of r-hLH+r-hFSH improves COH clinical outcomes in the IVF/ICSI cycle.

Topics: Case-Control Studies; Dietary Supplements; Female; Follicle Stimulating Hormone, Human; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Luteinizing Hormone; Male; Menotropins; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pregnancy; Retrospective Studies; Semen

Patients aged ≥35 years and DOR undergoing their first IVF/ICSI cycle were enrolled in this retrospective cohort study: 139 and 600 patients underwent the PPOS and mild stimulation protocols, respectively. The primary outcomes were cumulative clinical pregnancy rate (CCPR) and cumulative live birth rate (CLBR). The secondary outcomes were the number of oocytes retrieved and top-quality embryos.. There was nearly no significant difference of baseline characteristics between the two groups. Although a greater amount of total gonadotropin (1906.61 ± 631.04 IU vs. 997.72 ± 705.73 IU,. The PPOS protocol is an effective alternative to the mild stimulation protocol for advanced age patients with DOR, as it provides comparable reproductive outcomes and better control of premature LH surge. Further, more oocytes and top-quality embryos were obtained in the PPOS group, which had a positive association with conservative CCPR and CLBR.

Topics: Adult; Chorionic Gonadotropin; Clomiphene; Cohort Studies; Dydrogesterone; Female; Fertility Agents, Female; Fertilization in Vitro; Humans; Letrozole; Live Birth; Maternal Age; Medroxyprogesterone Acetate; Menotropins; Odds Ratio; Oocyte Retrieval; Ovarian Hyperstimulation Syndrome; Ovarian Reserve; Ovulation Induction; Pregnancy; Pregnancy Rate; Progestins; Retrospective Studies; Sperm Injections, Intracytoplasmic; Triptorelin Pamoate

Topics: Adult; Chorionic Gonadotropin; Combined Modality Therapy; Female; Fertility Agents, Female; Follicle Stimulating Hormone, Human; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Infertility, Female; Leuprolide; Living Donors; Menotropins; Nephrectomy; Oocyte Retrieval; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Recombinant Proteins; Renal Insufficiency; Severity of Illness Index; Treatment Outcome

Data on the incidence and severity of ovarian hyperstimulation syndrome (OHSS) in France are limited.. Prospective observational multicentric study (23 French centers of IVF) in a cohort of 421 women treated with highly purified hMG (HP-hMG) for the first or second cycle of IVF with or without ICSI. The primary objective was to assess the incidence of moderate to severe OHSS in this cohort.. At inclusion, 172 patients (40.9%) were considered at risk of OHSS by the physicians. The main measures for risk minimization taken by the physicians rested on initial dose of HP-hMG and protocol choice. At the end of the follow-up (4 months in average), the rate of OHSS moderate to severe was 2.4% (confidence interval 95%: 1.1-4.3%) for the studied IVF cycle. OHSS was severe for 3 women (0.7%) and moderate for 7 women (1.7%).. This rate of OHSS after IVF is at the lower limit of the rates reported in the literature for OHSS. This study brings reassuring epidemiological data on the rate of OHSS in women at risk. The measures taken by the physicians to minimize the risk of OHSS could have contributed to this low incidence.

Topics: Adult; Female; Fertilization in Vitro; France; Humans; Menotropins; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Prospective Studies; Risk Factors; Sperm Injections, Intracytoplasmic

The aim of the study was to assess the predictive value of vascular endothelial growth factor (VEGF), its soluble receptor - sVEGF-R1/sFlt1 and endocrine gland-derived vascular endothelial growth factor (EG-VEGF) concentrations in serum and follicular fluid (FF) for ovarian hyperstimulation syndrome (OHSS) in women undergoing controlled ovarian hyperstimulation (COH) protocols. Patients have been divided into 3 groups: control group on natural cycle, patients stimulated with GnRH agonist and patients stimulated with GnRH antagonist. The FF and serum concentrations of VEGF, EG-VEGF, sVEGF R1 and the expression of VEGF and EG-VEGF mRNA in GC in small and large follicles collected from patients were investigated. When we compared all patients in a trial, OHSS occurrence was correlated with higher level of sVEGF R1 and a lower level of VEGF in a follicular fluid from large follicles in a day of oocyte retrieval. The VEGF/sVEGF-R1 ratio for patients in COH groups, above which the risk of developing OHSS is very low (OR 0.1 (95% CI 0.01 - 0.29, P = 0.0006) was found to be 0.281 pg/ml, with AUC - 0.738, P = 0.042, (95% CI 0.656 - 0.82). High levels of sVEGF-R1 and low level of VEGF in FF on the day of oocyte retrieval correlate with OHSS regardless of the stimulation protocol.

Topics: Adult; Female; Fertilization in Vitro; Follicular Fluid; Gonadotropin-Releasing Hormone; Humans; Menotropins; Oocyte Retrieval; Ovarian Hyperstimulation Syndrome; RNA, Messenger; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor Receptor-1; Vascular Endothelial Growth Factor, Endocrine-Gland-Derived

Topics: Appendicitis; Chorionic Gonadotropin; Female; Humans; Menotropins; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Young Adult

To study whether intranasal GnRH agonist (GnRHa) can be effectively used for luteal support in high-responder patients undergoing fresh-embryo transfer after ovulation induction with the use of GnRHa.. Retrospective cohort study.. Private fertility clinic.. Forty-six high-responder patients were administered a GnRHa ovulation trigger to avoid ovarian hyperstimulation syndrome (OHSS), followed by 2 weeks of daily intranasal GnRHa (nafarelin) for luteal-phase support. No additional progesterone supplementation was administrated.. Intranasal GnRHa for luteal-phase support.. The primary outcome was ongoing clinical pregnancy rate.. High median progesterone levels were measured at midluteal phase and on the day of the first positive pregnancy test (190 nmol/L on both measures). We obtained 24 (52.1%) ongoing clinical pregnancies. None of the patients developed OHSS.. Intranasal GnRHa is effective in achieving luteal-phase support in high-responder patients triggered with GnRHa and avoiding OHSS.

Topics: Administration, Intranasal; Adult; Drug Administration Schedule; Embryo Transfer; Female; Fertility Agents, Female; Fertilization in Vitro; Follicle Stimulating Hormone, Human; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Infertility; Menotropins; Nafarelin; Oocyte Retrieval; Ovarian Hyperstimulation Syndrome; Ovulation; Ovulation Induction; Pregnancy; Pregnancy Rate; Recombinant Proteins; Retrospective Studies; Risk Factors; Treatment Outcome

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

A major cause of cycle cancellation during controlled ovarian hyperstimulation (COH) in women undergoing in vitro fertilization (IVF) is the occurrence of premature luteinizing hormone (LH) surges. Steroidal preparations can modulate the secretion of gonadotropins (Gn); however, few studies using progesterone to inhibit the premature LH surges in COH have been published. The purpose of the study was to evaluate the oral delivery of progesterone soft capsules (Utrogestan) to prevent LH surges from the follicular phase and to compare cycle characteristics as well as to evaluate pregnancy outcomes in subsequent frozen-thawed embryo transfer (FET) cycles. A total of 374 patients were enrolled in this retrospective study, among which 187 patients were simultaneously administered Utrogestan and human menopausal gonadotrophin (hMG) from cycle day 3 until the trigger day. A short protocol including 187 controls with comparable age, body mass index (BMI), infertility duration, and antral follicle count was also used. GnRH agonist (0.1 mg) or hCG (3000 IU) was used for a trigger when the dominant follicles matured. Viable embryos were cryopreserved for later transfer in both groups. The primary outcome was the number of oocytes retrieved. The secondary outcomes included the number of mature oocytes, incidence of premature LH surge, and clinical pregnancy outcomes from FET cycles. Consistent LH suppression was achieved during COH, with a range of 0.07 to 8.9 IU/L, and no premature LH surge was detected. The number of oocytes retrieved in the Utrogestan and hMG protocol was comparable with that in the short protocol (10.92 ± 5.74 vs 10.6 ± 6.22, P > 0.05), and the dose of hMG was higher than that used in the short protocol (1884.22 ± 439.47 IU vs 1446.26 ± 550.48 IU, P < 0.05). No significant between-group difference was observed in the mature oocyte rate (88.88% vs 90.12%), cleavage rate (96.58% vs 96.58%), clinical pregnancy rate (54.27% vs 51.65%), or implantation rate (33.59% vs 34.02%). The study shows that Utrogestan is an effective oral alternative for preventing premature LH surges in women undergoing COH, which will help to establish a convenient user regimen in combination with FET.

Topics: Adult; Female; Fertility Agents, Female; Fertilization in Vitro; Humans; Luteinizing Hormone; Menotropins; Oocytes; Ovarian Hyperstimulation Syndrome; Progesterone; Progestins; Retrospective Studies

To evaluate the reproductive performance and safety of gonadotropin-stimulated intrauterine insemination (IUI) cycles in women at risk for ovarian hyperstimulation syndrome (OHSS) when final follicle maturation was induced using a gonadotropin-releasing hormone (GnRH) agonist.. Thirty-three women presenting with a history of cancelled ovarian stimulation for fear of OHSS, underwent repeat gonadotropin ovarian stimulation for IUI. They were all found to be at high-risk for OHSS once more, and were counseled to receive a GnRH agonist to trigger final follicle maturation before insemination. GnRH agonist trigger of ovulation (triptorelin) was given subcutaneously every 12 hours in three repeated doses: 0.3, 0.2, 0.2 mg, respectively.. Induction with the agonist was associated with a 30.3% take-home pregnancy rate and 20% miscarriage rate. Multiple pregnancy rates were 26.7%. There were no reported cases of clinically significant moderate/severe ovarian hyperstimulation syndrome.. The use of a GnRH agonist to trigger final follicle maturation in stimulated cycles of hyper responders was associated with a favorable reproductive outcome and no incidence of OHSS. The rate of multiple pregnancies nevertheless was found to be uncontrollably elevated, raising serious concerns regarding the safety of this protocol in standard clinical practice in the context of IUI.

Topics: Adult; Female; Fertility Agents, Female; Gonadotropin-Releasing Hormone; Humans; Insemination, Artificial; Menotropins; Ovarian Follicle; Ovarian Hyperstimulation Syndrome; Pregnancy; Pregnancy, Multiple; Triptorelin Pamoate

Previous studies have reported conflicting results for the comparative doses of recombinant follicle stimulating hormone (rFSH) and highly purified human menopausal gonadotrophin (hMG-HP) required per cycle of in vitro fertilisation (IVF); the aim of this study was to determine the average total usage of rFSH versus hMG-HP in a 'real-world' setting using routine clinical practice.. This retrospective chart review of databases from four European countries investigated gonadotrophin usage, oocyte and embryo yield, and pregnancy outcomes in IVF cycles (± intra-cytoplasmic sperm injection) using rFSH or hMG-HP alone. Included patients met the National Institute for Health and Clinical Excellence (NICE) guideline criteria for IVF and received either rFSH or hMG-HP. Statistical tests were conducted at 5% significance using Chi-square or t-tests.. Of 30,630 IVF cycles included in this review, 74% used rFSH and 26% used hMG-HP. A significantly lower drug usage per cycle for rFSH than hMG-HP (2072.53 +/- 76.73 IU vs. 2540.14 +/- 883.08 IU, 22.6% higher for hMG-HP; p < 0.01) was demonstrated. The median starting dose was also significantly lower for rFSH than for hMG-HP (150 IU vs. 225 IU, 50% higher for hMG-HP, p < 0.01). The average oocyte yield per IVF cycle in patients treated with rFSH was significantly greater than with hMG-HP (10.80 +/- 6.02 vs. 9.77 +/- 5.53; p < 0.01), as was the average mature oocyte yield (8.58 +/- 5.27 vs. 7.72 +/- 4.59; p < 0.01). No significant differences were observed in pregnancy outcomes including spontaneous abortion between the two treatments. There was a significantly higher rate of OHSS (all grades) with rFSH (18.92% vs. 14.09%; p < 0.0001). The hospitalisation rate due to OHSS was low but significantly higher in the rFSH group (1.07% of cycles started vs. 0.67% of cycles started with rFSH and hMG-HP, respectively; p = 0.002).. Based on these results, IVF treatment cycles with rFSH yield statistically more oocytes (and more mature oocytes), using significantly less IU per cycle, versus hMG-HP. The incidence of all OHSS and hospitalisations due to OHSS was significantly higher in the rFSH cycles compared to the hMG-HP cycles. However, the absolute incidence of hospitalisations due to OHSS was similar to that reported previously. These results suggest that the perceived required dosage with rFSH is currently over-estimated, and the higher unit cost of rFSH may be offset by a lower required dosage compared with hMG-HP.

Topics: Adult; Female; Fertilization in Vitro; Follicle Stimulating Hormone; Humans; Menotropins; Oocyte Retrieval; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pregnancy; Pregnancy Outcome; Recombinant Proteins

A challenge of in vitro maturation (IVM) treatment in some women is insufficient development of the endometrium prior to embryo transfer.. Retrospective study.. McGill Reproductive Center, Montreal, Canada.. Women with endometrial thickness <6 mm on days 6-10 ultrasound (US) scan of IVM treatment.. In the human menopausal gonadotropin (hMG) group, 150 IU/day of hMG was started and in the estradiol group, 6 to 12 mg/day of micronized 17beta-estradiol was initiated. Additional US scans were performed 2 to 3 days apart, until endometrial thickness reached > or =8 mm or a dominant follicle (>10 mm) was identified.. Endometrial lining before oocyte retrival.. In both groups endometrial lining significantly thickened following treatment. However, hMG treatment resulted in a higher number of follicles > or =7 mm compared to estradiol (7.4 +/- 4.8 vs. 3.4 +/- 2.5, respectively) and a significantly higher percentage of mature oocytes that were identified on the day of oocyte retrieval (in vivo matured oocytes) (15.1% vs. 10.5%).. In IVM designated cycles with a thin endometrium both low-dose hMG and micronized 17beta-estradiol supplementation significantly improve endometrial thickness. However, low-dose hMG results in larger follicles and a greater number of in vivo matured oocytes.

Topics: Adult; Cell Proliferation; Dose-Response Relationship, Drug; Embryo Transfer; Endometrium; Estradiol; Female; Fertility Agents, Female; Fertilization in Vitro; Humans; Menotropins; Menstrual Cycle; Oocytes; Ovarian Hyperstimulation Syndrome; Retrospective Studies; Risk Factors; Treatment Outcome; Ultrasonography

Topics: Adult; Estradiol; Female; Humans; Hypothyroidism; Menotropins; Ovarian Hyperstimulation Syndrome; Thyroid Gland; Thyrotropin; Thyroxine

To investigate if the combination of clomiphene citrate, hMG, and cetrorelix (CC/hMG/cetrorelix protocol) can be applied to patients who had excessive response to GnRHa long protocol.. Fifty patients who coasted and failed to conceive in their first cycles stimulated with GnRHa long protocol were stimulated with CC/hMG/cetrorelix protocol. The peak serum estradiol levels, the need of coasting and prolonged coasting (>/=4 days), and the incidences of OHSS were compared.. The peak estradiol level was significantly lower with CC/hMG/cetrorelix protocol compared to GnRHa long protocol. With CC/hMG/cetrorelix protocol, only four patients (8%) needed coasting and no one coasted >/=4 days. In contrast, in the first cycles, 11 patients (22%) needed coasting >/=4 days. The incidence of moderate OHSS was significantly lower with CC/hMG/cetrorelix protocol.. The CC/hMG/cetrorelix protocol is an acceptable alternative protocol for patients who had excessive response to GnRHa long protocol.

Topics: Adult; Clomiphene; Drug Therapy, Combination; Embryo Transfer; Estradiol; Female; Fertility Agents, Female; Fertilization in Vitro; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Menotropins; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pregnancy; Pregnancy Rate; Prospective Studies; Sperm Injections, Intracytoplasmic; Superovulation; Treatment Outcome

This study examined the effects of human menopausal gonadotrophin (HMG) or human chorionic gonadotrophin (HCG) priming on cumulus-oocyte complex (COC) morphology, oocyte maturation and embryo development in patients undergoing in-vitro maturation (IVM) cycles. The patients were primed with nothing (group 1), low-dose HMG (group 2) or 10,000 IU HCG (group 3) before oocyte retrieval. COC with dispersed cumulus cell appearance was only observed in group 3. In addition, 11% of metaphase II stage oocytes at the time of retrieval were collected from group 3. Oocyte maturation in vitro in group 3 was faster than that in groups 1 and 2. The blastocyst development rate of residual embryos after embryo transfer in group 3 was significantly higher than that of groups 1 and 2 (P < 0.05). These results suggest that HCG priming may stimulate the COC, promote oocyte maturation, and improve developmental competence in IVM cycles.

Topics: Adult; Chorionic Gonadotropin; Embryo Transfer; Female; Fertilization in Vitro; Humans; Menotropins; Oocyte Donation; Oocytes; Ovarian Hyperstimulation Syndrome; Retrospective Studies

Ovarian hyperstimulation syndrome (OHSS) is a serious and potentially life-threatening complication following ovarian stimulation for in vitro fertilization (IVF). Coasting is the practice whereby the gonadotrophins are withheld and the administration of human chorionic gonadotrophin (hCG) is delayed until serum oestradiol (E2) has decreased to what is considered to be a safe level, to prevent the onset of OHSS. This study aimed to assess the length of coasting on the reproductive outcome in women at risk of developing OHSS. Coasting was undertaken when the serum E2 concentrations were > or = 17000 pmol/L but < 21000 pmol/L. Daily E2 measurements were performed and hCG was administered when hormone levels decreased to < 17000 pmol/L. Eighty-one women who had their stimulation cycles coasted were grouped according to the number of coasting days. Severe OHSS occurred in one case, which represented 1.2% of patients who underwent coasting because of an increased risk of developing the syndrome. No difference was found between cycles coasted for 1 - 3 days and cycles coasted for > or = 4 days in terms of oocyte maturity, fertilization and embryo cleavage rates. Women in whom coasting lasted for > or = 4 days had significantly fewer oocytes retrieved (P < 0.05) and decreased implantation rate (P < 0.05) compared to those coasted for 1 - 3 days. Pregnancy rate/embryo transfer and live birth rate did not differ between groups. In conclusion, coasting appears to decrease the risk of OHSS without compromising the IVF cycle pregnancy outcome. Prolonged coasting is, however, associated with reduced implantation rates, perhaps due to the deleterious effects on the endometrium rather than the oocytes.

Topics: Chorionic Gonadotropin; Clinical Protocols; Estradiol; Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Humans; Menotropins; Ovarian Hyperstimulation Syndrome; Pregnancy; Pregnancy Outcome; Retrospective Studies; Risk Factors; Sperm Injections, Intracytoplasmic; Time Factors

To demonstrate that folliculogenesis can be sustained with 200 IU human chorionic gonadotropins (hCG) after FSH-priming and result in pregnancy in women with estrogenic ovulatory dysfunction and risk factors for severe ovarian hyperstimulation syndrome (OHSS).. Three women with infertility associated with estrogenic ovulatory dysfunction and hyperinsulinemia who appeared to be at high risk for severe OHSS during gonadotropin therapy.. After 10 days of receiving either 150 IU hMG or recombinant FSH, patients were switched to 200 IU hCG/day alone for 2-3 days. 5,000 IU of hCG was then administered followed by either home intercourse, intrauterine insemination or transvaginal oocyte retrieval-embryo transfer.. Endovaginal ultrasound measurement of follicle number and size, serum estradiol levels, symptoms of ovarian hyperstimulation, pregnancy test, and evaluation of pregnancy by transvaginal ultrasound.. After discontinuation of hMG or recombinant FSH, serum estradiol concentrations continued to rise, and follicles >14 mm continued to grow during low-dose hCG administration. All women conceived without developing symptoms of OHSS. Pregnancy outcomes achieved include a term singleton delivery, a term twin delivery, and triplets delivered at 31 weeks gestation.. The use of low-dose hCG alone is sufficient for supporting the late stages of folliculogenesis in women with estrogenic ovulatory dysfunction. This ovulation induction regimen appears to support the follicular growth of larger follicles while decreasing the number of smaller preovulatory follicles, thereby reducing a known risk factor for OHSS. We report on the positive pregnancy outcomes in 3 women with estrogenic ovulatory dysfunction and clinically appeared to be at high risk for developing severe OHSS who safely underwent this protocol.

Topics: Adult; Chorionic Gonadotropin; Estradiol; Female; Fertility Agents, Female; Follicle Stimulating Hormone; Humans; Infertility, Female; Male; Menotropins; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pregnancy; Pregnancy Outcome

We attempted ovarian stimulation using gonadotropins in 14 chimpanzees. Subjects were given a single administration of leuprorelin acetate, followed by repeated administration of human menopausal gonadotropin (hMG) for 16-21 days. During the dosing period, the ovarian follicle diameter and count were measured by transvaginal ultrasonography. The hormone administration induced the development of multiple follicles, and multiple oocytes were subsequently retrieved. However, the follicle count was decreased, suggesting atresia, in some subjects. Statistically, the final follicle diameter was dependent on the dosing duration and the hMG dose in the late stage, while the maximum follicle count during hMG administration was dependent on age and the hMG dose in the early stage. Five subjects showed mild ovarian hyperstimulation syndrome (OHSS)-like symptoms with a high serum estradiol (E2) concentration. These results suggest that leuprorelin acetate plus hMG administration successfully stimulates the development of multiple ovarian follicles for oocyte retrieval and that the serum E2 concentration is predictive of OHSS-like symptoms in chimpanzees.

Topics: Animals; Estradiol; Female; Follicular Atresia; Humans; Kinetics; Leuprolide; Menotropins; Monkey Diseases; Oocytes; Ovarian Follicle; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pan troglodytes; Progesterone; Superovulation; Ultrasonography

The aim of this study is to report a large series of patients (n = 1223) at risk of developing ovarian hyperstimulation syndrome (OHSS) who underwent coasting.. Coasting started when the leading follicle reached 16 mm and continued until the estradiol (E2) level fell to 3000 pg/ml.. The E2 level at the start of coasting was (mean +/ SD) 6408 +/- 446 and it fell to 2755 +/- 650 on the day of HCG injection, after (mean +/- SD) 2.89 +/- 0.94 days. The results were analysed according to the duration of coasting (< or = 3 days, group I: n = 983; >3 days, group II: n = 240). The number of oocytes retrieved was (mean SD) 16.45 +/- 6.25 and 14.93 +/- 6.01 in groups I and II respectively (P < 0.05). The fertilization rates were 63 and 65% in groups I and II respectively (P > 0.05). The implantation and clinical pregnancy rates were 26 and 52% in group I compared to 18 and 36% in group II respectively (P < 0.05). Severe OHSS occurred in 16 cases, which represented 0.13% of all stimulated cycles, and 1.3% of patients who were at risk of developing OHSS.. Our protocol of coasting was an effective measure in the prevention of OHSS, without jeopardizing the ICSI outcome. Coasting for >3 days is associated with a moderate decrease in the pregnancy rate.

Topics: Adult; Chorionic Gonadotropin; Cohort Studies; Drug Therapy, Combination; Estradiol; Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Humans; Menotropins; Ovarian Follicle; Ovarian Hyperstimulation Syndrome; Pregnancy; Retrospective Studies; Risk; Sperm Injections, Intracytoplasmic; Treatment Outcome; Triptorelin Pamoate

We report the case of a 32-year-old woman suffering from severe liver dysfunction in the course of ovarian hyperstimulation syndrome (OHSS). Complications occurred after successful fertilization subsequent to ovarian stimulation with human menopausal gonadotropin followed by ovulation induction with human chorionic gonadotropin. Because of nausea, vomiting, abdominal distention and enlarged ovaries on an ultrasound examination, she was admitted on the diagnosis of OHSS. During the course of hospitalization severe hepatic injury developed. An increase of more than 100-fold in blood aminotransferase activity was observed. Applied treatment resulted in gradual reduction of ovarian size and resolution of ascites, as well as pleural and pericardial effusions. The patient was discharged from hospital after 46 days. Follow-up examinations at the 13th and 32nd weeks of gestation did not reveal any abnormalities. Pregnancy developed without complications and the woman went into spontaneous labor, giving birth to a viable child at 38 weeks' gestation. Taking into account the above case and previously published reports, the issue of liver dysfunction may have a great impact on the understanding both the pathology and the treatment of OHSS.

Topics: Adult; Alanine Transaminase; Aspartate Aminotransferases; Biopsy; Chorionic Gonadotropin; Female; Humans; Liver Diseases; Menotropins; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pregnancy; Pregnancy 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

Human menopausal gonadotropin (hMG, 75 IU/body/day) and a gonadotropin-releasing hormone (GnRH) agonist buserelin (1, 10, 100 microg/kg/day) were simultaneously administered to female rabbits by the subcutaneous route for 7 days, and the effects on organ weights, plasma hormones and weight of ascitic fluid were examined. Treatment with hMG increased the ovarian weight, plasma estradiol and weight of ascites, thus indicating that ovarian hyperstimulation syndrome had been induced. Simultaneous treatment with buserelin decreased the changes induced by hMG. GnRH agonists can thus be surmised to reduce the severity of ovarian hyperstimulation syndrome in the rabbit. However, caution is needed when extrapolating the results of this rabbit model to humans.

Topics: Animals; Ascites; Buserelin; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Therapy, Combination; Estradiol; Female; Gonadotropin-Releasing Hormone; Menotropins; Organ Size; Ovarian Hyperstimulation Syndrome; Ovary; Progesterone; Rabbits; Uterus

The ovarian hyperstimulation syndrome (OHSS) is an iatrogenic, unpredictable and potentially life-threatening complication in patients submitted to pharmacological ovarian stimulation. Information on risk factors, etiopathogenetic mechanisms, prevention strategies and therapeutic management is continuously updated. The present study retrospectively analyzed 123 women affected by different grades of OHSS as a result of pharmacological ovulation induction. Hospital admission was suggested in 14 patients with severe OHSS, whereas patients with moderate or mild OHSS were followed in the out-patient section of our department. The results confirmed the efficacy of the therapeutic scheme adopted. The syndrome is localized to the ovaries at the time that the condition is triggered; when organs different from the ovaries become involved, OHSS assumes systemic aspects. The different clinical signs are the basis of a proposal of a local and systemic classification.

Topics: Adult; Ascites; Chorionic Gonadotropin; Creatinine; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Hematocrit; Humans; Menotropins; Ovarian Hyperstimulation Syndrome; Ovary; Ovulation Induction; Respiratory Distress Syndrome; Retrospective Studies

Ovarian hyperstimulation syndrome (OHSS), a highly dangerous and incompletely understood complication of ovulation induction with exogenous gonadotrophins, can include haemoconcentration, hypovolaemia, hypotension, acute renal insufficiency, thromboembolism and ultimately death. Using intravital microscopy, we examined microvascular permeability and leukocyte-endothelial cell interactions in the rat mesenteric microcirculation associated with induction of ovulation.. In female rats treated with hMG and hCG, mesenteric venules were observed by intravital microscopy assisted by a video imager. Erythrocyte velocity was monitored, and rolling and adhesion of leukocytes were studied by transmission video images. Transvascular leakage of fluorescein isothiocyanate-labelled albumin was assessed by epi-illumination.. Administration of hMG and hCG significantly increased vascular protein leakage within a few hours, and also reduced rolling velocities of leukocytes in venules and increased numbers of leukocytes adherent to endothelium at 16 h following hCG injection. The administration of antibodies against intracellular adhesion molecule (ICAM)-1 inhibited these reactions.. By induction of ovulation, vascular permeability is increased not only at the surface of the ovary but also in the mesentery. Alteration of leukocyte behaviour in the microcirculation through mechanisms involving ICAM-1 is one likely cause of the protein leakage.

Topics: Animals; Antibodies; Capillary Permeability; Cell Adhesion; Chorionic Gonadotropin; Endothelium, Vascular; Female; Intercellular Adhesion Molecule-1; Leukocytes; Menotropins; Mesentery; Microcirculation; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Rats; Rats, Wistar

To assess whether ovarian volume of World Health Organization II anovulatory patients in the early follicular phase predicts the response to ovulation induction with gonadotropins.. Retrospective data analysis of two prospective, randomized, multicenter studies.. Clinical development unit of biotechnology company.. Four hundred sixty-five World Health Organization II anovulatory patients undergoing ovulation induction.. Ovarian response to stimulation, ovulation (mid-luteal serum progesterone > 30 nmol/L), cancellation rate, pregnancy rate, and incidence of the ovarian hyperstimulation syndrome (OHSS) according to baseline ovarian volume (day 2-5) before stimulation.. Mean ovarian volume was 11.55 +/- 6.0 cm(3) (range, 0.8-49.3 cm(3)). Small ovarian volume was associated with lower rates of cycle cancellation owing to risk for OHSS (3 vs. 29 patients [2.8% vs. 9%]). Patients with small ovarian volume (<7.25 cm(3)) required fewer ampules of FSH (1373 IU vs. 1629 IU) and shorter duration of stimulation (16 vs. 18.1 days) and had higher ovulation rate than did patients with mid-range and larger ovarian volume (84.3% vs. 69.1% and 68.8%, respectively). The clinical pregnancy rate per cycle of hCG administration was similar in the three groups (25.8%, 28.1%, and 27.5%).. World Health Organization II anovulatory women with medium-sized or large ovaries who are undergoing low-dose gonadotropin stimulation for ovulation induction may have higher risk for OHSS than do women with small ovaries. Women with small ovaries who meet criteria for administration of hCG respond better to ovulation induction and have a similar likelihood of conceiving compared with women with larger ovaries.

Topics: Adult; Anovulation; Female; Fertility Agents, Female; Follicle Stimulating Hormone; Follicle Stimulating Hormone, Human; Follicular Phase; Humans; Menotropins; Ovarian Hyperstimulation Syndrome; Ovary; Ovulation Induction; Predictive Value of Tests; Prospective Studies; Randomized Controlled Trials as Topic; Recombinant Proteins; Treatment Outcome

Topics: Adult; Diagnosis, Differential; Female; Humans; Infertility, Female; Menotropins; Ovarian Hyperstimulation Syndrome; Pelvic Pain; Pregnancy; Ultrasonography, Prenatal

To investigate the hemodynamic state in the ovarian hyperstimulation syndrome (OHSS) in the rabbit model and to determine the role of angiotensin II in the pathophysiology of this syndrome.. Experimental study.. Physiology laboratory.. Female New Zealand rabbits were studied; 16 rabbits were stimulated with gonadotropins, and 6 were controls. Six of the stimulated rabbits received additional treatment with captopril.. Cardiac index, blood pressure, and heart rate were recorded.. Gonadotropin-stimulated rabbits had significant enlargement of ovaries that was not modified by captopril. Ascites was present in 80% of animals in the OHSS group; captopril significantly decreased the incidence and volume of ascites. The three groups did not differ in blood pressure, heart rate, cardiac index, and total peripheral resistance.. In rabbits with OHSS, ascites are a primary event. Such animals are normotensive and have normal vascular resistance and cardiac index. Angiotensin-converting enzyme inhibition decreases the incidence of OHSS in the rabbit model by 30%, suggesting that angiotensin II may play a role in the formation of ascites.

Topics: Angiotensin II; Animals; Ascites; Blood Pressure; Cardiac Output; Chorionic Gonadotropin; Female; Heart Rate; Hemodynamics; Menotropins; Ovarian Hyperstimulation Syndrome; Ovary; Rabbits

Topics: Female; Follicle Stimulating Hormone; Humans; Luteinizing Hormone; Menotropins; Ovarian Follicle; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Receptors, LH

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 evaluate whether differences in plasma vascular endothelial growth factor(165) (VEGF(165)) concentrations exist during gonadotropin stimulation in IVF patients developing severe ovarian hyperstimulation syndrome (OHSS) compared to matched controls.. Prospective cohort study with comparison of 15 OHSS cases with 30 matched (age, follicle numbers, pregnancy) controls. Unpaired students t-test was used to evaluate differences between the OHSS and control group and correlations were calculated with Pearson's test.. Plasma levels of VEGF(165), at four time-points from start of gonadotropin stimulation to embryo transfer (ET), were compared and related to steroid levels and ultrasound data. There were no differences between OHSS and control patients in plasma VEGF(165) levels at any of the four time points, which were compared. The mean levels were between 53--83 pg ml(-1) and 64--83 pg ml(-1) in the OHSS and control group, respectively. Positive correlations existed between total number of follicles, number of large (>15 mm) follicles and VEGF(165) at day of oocyte aspiration and between VEGF(165) and progesterone at ET in the control group, but not in the OHSS group.. Patients developing OHSS do not have raised plasma VEGF(165) levels during gonadotropin stimulation. The lack of positive correlation between VEGF(165) levels and follicle numbers/progesterone in the OHSS group, suggests a disruption in OHSS of the normal controlled follicular VEGF expression.

Topics: Adult; Ascitic Fluid; Chorionic Gonadotropin; Cohort Studies; Embryo Transfer; Endothelial Growth Factors; Female; Fertilization in Vitro; Follicle Stimulating Hormone; Gonadotropins; Humans; Lymphokines; Menotropins; Ovarian Hyperstimulation Syndrome; Pregnancy; Prospective Studies; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors

The purpose of this study was to evaluate the effectiveness of combined approach on the prevention of severe ovarian hyperstimulation syndrome (OHSS) in high risk patients undergoing controlled ovarian hyperstimulation for IVF. The combined approach consisted of: (1) step-down administration of gonadotropins; (2) lowering the dose of human chorionic gonadotropin; (3) intravenous albumin infusion at the time of oocyte retrieval and (4) progesterone use for luteal support. Total of 87 high risk patients with a serum estradiol level >11,010 pmol/l or 3000 pg/ml on HCG day were managed by this combined approach and their results were compared with 274 low risk patients. In all high risk patients, the gonadotrophin dose were decreased starting as early as on day 4 of ovarian stimulation as necessary, ovulation was triggered by a decreased HCG dose of 5000-7000 IU according to the level of estradiol, intravenous infusion of 20% human albumin, 50-100ml were given just 1h before the oocyte retrieval and luteal support was provided either by 50mg progesterone in oil, IM or 600 mg micronized progesterone orally or vaginally until the day of beta-HCG determination. All patients were followed by serial ultrasonographic examinations and complete blood count analysis after embryo transfer to detect the early signs of OHSS and to allow early intervention. Age and duration of infertility were similar in both groups. Although the number of gonadotrophin ampoules used (22.7 +/- 4.7 versus 27.8+/-3.7; P<0.05) was significantly lower, estradiol levels (16,764 +/- 6936 pmol/l versus 8870 +/- 2456 pmol/l; P<0.05) and mean number of oocytes (18.3 +/- 5.9 versus 10.6+/-5.4; P<0.05) were significantly higher in study group. There was no significant difference between groups in terms of the mean number of transferred embryos (3.2 +/- 1.1 versus 3.4+/-1.1) and rate of pregnancies (50.5% versus 40.1%). There was only one moderate and no severe OHSS case in the high risk group, while five moderate and one severe OHSS cases developed in the control group consisting of low risk patients. In conclusion, intravenous albumin combined with low dose HCG, early step-down administration of gonadotropins and progesterone use for luteal support, so called combined approach, proved to be effective in the prevention of severe ovarian hyperstimulation syndrome in documented high risk patients.

Topics: Adult; Chorionic Gonadotropin; Estradiol; Female; Fertilization in Vitro; Follicle Stimulating Hormone; Humans; Infusions, Intravenous; Menotropins; Oocytes; Ovarian Hyperstimulation Syndrome; Progesterone; Serum Albumin; Sperm Injections, Intracytoplasmic; Tissue and Organ Harvesting; Turkey

To report two cases of coasting during receipt of GnRH antagonists.. Case report.. University hospital.. One 27-year-old and one 28-year-old woman, both with risk factors for the ovarian hyperstimulation syndrome (OHSS).. Two IVF treatments during which hMG treatment was stopped until E2 decreased to a safer level during receipt of GnRH antagonist.. Development of OHSS and pregnancy.. Embryos were transferred in both women. Neither woman developed OHSS and one ongoing pregnancy was obtained.. Coasting is feasible when a GnRH antagonist is used during IVF. Further studies are needed to evaluate its preventive role in OHSS.

Topics: Adult; Drug Administration Schedule; Estradiol; Feasibility Studies; Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Humans; Menotropins; Ovarian Hyperstimulation Syndrome; Pregnancy; Pregnancy Rate

The ovarian hyperstimulation syndrome (OHSS) following ovulation induction is characterized by a cystic enlargement of the ovaries with an acute third space fluid sequestration. Inflammatory cytokines mediate the inflammatory response (IL-1, IL-2, IL-6, IL-8, TNFalpha) and play a crucial role in the pathogenesis of OHSS.. To determine the role of the anti-inflammatory cytokine interleukin-10 (IL-10) in OHSS and to examine its correlation with 17beta-estradiol and progesterone.. Peritoneal fluid and serum samples were collected from 9 patients with severe OHSS after ovulation induction by administration of GnRH-analogues followed by hMG (n=5) or recombinant FSH (n=4). Patients (n=19) without pathological findings at laparoscopy served as non-pregnant controls and pregnant women (n=14) between 7 and 16 weeks of gestation served as positive controls. Samples were assayed for IL-10 by commercially available ELISA and for for 17beta-estradiol and progesterone by RIA. Statistical analysis was performed by non-parametric Mann-Whitney U-test and results are presented as the median and range.. OHSS patients had significantly higher peritoneal fluid IL-10, 17beta-estradiol and progesterone levels than patients during early pregnancy and than the control group. No correlation was found between peritoneal fluid or serum IL-10 and 17beta-estradiol or progesterone in the different groups. Serum 17beta-estradiol and progesterone, but not serum IL-10 levels were elevated in OHSS and during early pregnancy.. High concentrations of IL-10 in peritoneal fluid suggest a role of this anti-inflammatory cytokine during OHSS. 17beta-estradiol and progesterone were elevated in peritoneal fluid and serum during OHSS but no correlation with IL-10 concentrations was found. Therefore, we assume that IL-10 has a role in OHSS as a local mediator of inflammation, however, it presents different aspects of the OHSS than the sex steroids 17beta-estradiol and progesterone.

Topics: Adult; Ascitic Fluid; Chorionic Gonadotropin; Estradiol; Female; Fertilization in Vitro; Follicle Stimulating Hormone; Gonadal Steroid Hormones; Gonadotropin-Releasing Hormone; Humans; Interleukin-10; Menotropins; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pregnancy; Progesterone; Recombinant Proteins

The ovarian hyperstimulation treatment increases results of in vitro fertilization. However, the risk of ovarian hyperstimulation syndrome must be carefully evaluated for each patient. An excessive response increases complication and cancellation rates. Coasting could be applied when an excessive response occurred. This method requires stopping gonadotropin administration while GnRH agonist is continued. When the estradiol rate decreases, the hCG administration is allowed. In the literature, results shows adequate pregnancy rates, between 26 and 64%. It seems oocyte quality was not spoiled. However, coasting does not eliminate definitively the risk of ovarian hyperstimulation syndrome. Coasting method could be a safe and efficient method to treat an excessive ovarian response during in vitro fertilization protocol. Pregnancy rates seem to be preserved.

Topics: Chorionic Gonadotropin; Clinical Protocols; Drug Monitoring; Embryo Transfer; Estradiol; Female; Fertility Agents, Female; Follicular Atresia; Gonadotropin-Releasing Hormone; Humans; Infertility, Female; Menotropins; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pregnancy; Pregnancy Outcome; Risk Factors; Ultrasonography

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

Our purpose was to compare oocyte nuclear maturation and embryo quality after pituitary down-regulation and ovarian stimulation with highly purified follicle-stimulating hormone (FSH) or human menopausal gonadotropin (HMG).. Fifty-five patients 37 years of age or younger who were undergoing in vitro fertilization (IVF)-intracytoplasmic sperm injection (ICSI) were evaluated retrospectively. In all cases, male factor was the only indication for treatment, with no female-related factors identified. Following pituitary down-regulation, patients were stimulated with hMG (n = 20) or highly purified FSH (n = 35). Main outcome measures included ovarian response to stimulation, oocyte maturity, and ICSI fertilization results. Secondary outcome measures included pregnancy rates and outcome.. The ovarian response to stimulation was similar for the two groups, as were the percentage of metaphase II oocytes, fertilization and cleavage rates, and number and quality of transferred and cryopreserved embryos. Cycle outcome was comparable.. In normogonadotropic subjects, monocomponent therapy with highly purified FSH is as effective as hMG in stimulating ovarian follicular development, synchronization of oocyte maturation, and IVF-ICSI outcome. Our findings support the conclusion that the luteinizing hormone component in the stimulation protocol is unnecessary.

Topics: Adolescent; Adult; Cellular Senescence; Cytoplasm; Female; Fertility Agents, Female; Fertilization in Vitro; Follicle Stimulating Hormone; Humans; Male; Menotropins; Microinjections; Oocytes; Ovarian Hyperstimulation Syndrome; Pregnancy; Pregnancy Rate; Retrospective Studies; Treatment Outcome

The purpose of the present study is to determine the efficacy of an artificial intrauterine insemination program with frozen donor sperm and controlled ovarian hyperstimulation as an alternative therapy for infertility cause by hypergonadotropic azoospermia. Two hundred forty three insemination cycles with frozen donor sperm were analyzed. Clomiphene citrate, pure FSH, recombinant FSH or human menopausal gonadotropins were utilized for ovulation induction; human corionic gonadotropin (hCG), 10,000 IU, was administered when one or more dominant follicles with diameter > or = 16 mm were present; intrauterine insemination was performed 36 hours after the hCG injection. The pregnancy rate per cycle was 19.9%, and the cumulative pregnancy rate was 59.3%. It is concluded that intrauterine insemination with frozen donor sperm and ovulation induction is a good alternative for male factor infertility with no available treatment.

Topics: Chorionic Gonadotropin; Clomiphene; Cryopreservation; Female; Follicle Stimulating Hormone; Humans; Infertility, Male; Insemination, Artificial; Male; Menotropins; Oligospermia; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pregnancy; Pregnancy Outcome; Sperm Banks

There is an increasing interest in retrieving immature oocytes in the absence of or with limited gonadotrophin exposure, with the aim of maturing them in vitro for embryo transfer purposes. The aim of this report is to present our experience of fertilization, embryonic development and pregnancies from in-vitro maturation cycles. A total of 18 patients underwent 21 cycles in which an average of 8.1 immature oocytes was retrieved after limited exposure to human menopausal gonadotrophin (HMG) and no exposure to human chorionic gonadotrophin (HCG). In one cycle, no oocytes were recovered. The oocytes were cultured for 44 h and 121 oocytes which reached MII were injected with a single spermatozoon. A total of 71 oocytes showed two pronuclei and 53 zygotes cleaved. Forty-four embryos were transferred in 17 cycles. Five weeks after embryo transfer, ultrasound examination indicated the presence of one gestational sac and one fetal heart beat in two patients. The results suggest that in-vitro matured oocytes can undergo fertilization and the resulting embryos may result in pregnancies. However, the success rate was not sufficient to recommend widespread use of the technique without further research.

Topics: Cytoplasm; Embryo Transfer; Embryonic and Fetal Development; Female; Fertilization in Vitro; Humans; Infertility, Female; Male; Menotropins; Microinjections; Oocytes; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pregnancy; Spermatozoa

A 26-year-old woman on human menopausal gonadotrophin-human chorionic gonadotrophin therapy for sterility showed multiple cerebral infarctions associated with ovarian hyperstimulation syndrome. A hypercoagulable state (hemoconcentration, increased plasma levels of D-dimer and thrombin-antithrombin III complex, and decreased protein S activity) was associated with her thromboembolic events. Cerebral infarction associated with mild neurologic deficits may be overlooked in patients with ovarian hyperstimulation syndrome.

Topics: Adult; Antithrombin III; Brain; Cerebral Angiography; Cerebral Infarction; Chorionic Gonadotropin; Female; Fertility Agents, Female; Humans; Infertility, Female; Magnetic Resonance Imaging; Menotropins; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Peptide Hydrolases; Protein S; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed

A 26-year-old married woman was admitted to our hospital because of massive ascites and hepatic injury. The patient had been treated with human menopausal gonadotropin and clomiphene citrate to prevent recurrence of spontaneous abortions. About 1 month later, she developed upper abdominal pain and noticed dark urine. On admission, she had elevated concentrations of serum transaminases with an asparate aminotransferase of 127 IU/L and alanine aminotransferase of 194 IU/L. An abdominal ultrasound showed massive ascites. Her serum concentration of estradiol was high at 12,100 pg/mL, which was much greater than the value of early stage of pregnancy (2,279-7,353 pg/mL). She was thus diagnosed as having ovarian hyperstimulation syndrome. Following a period of bed rest, her liver function normalized and the ascites disappeared. Based on the above findings, the patient was considered to have suffered from ovarian hyperstimulation syndrome, complicated by hepatic injury.

Topics: Abortion, Spontaneous; Adult; Bed Rest; Capillary Permeability; Chemical and Drug Induced Liver Injury; Clomiphene; Female; Fertility Agents, Female; Humans; Liver; Liver Diseases; Menotropins; Ovarian Hyperstimulation Syndrome; Pregnancy; Pregnancy Trimester, First

Our purpose was to test whether age-related changes in antral follicle counts can predict the pregnancy outcome in the early follicular phase of a controlled ovarian hyperstimulation/intrauterine insemination (COH/IUI) program.. A selected group of 107 women (36 healthy women requesting child sex preselection, 52 women with unexplained infertility, and 19 with minimal endometriosis) who underwent controlled ovarian hyperstimulation with clomiphene citrate (CC) plus human menopausal gonadotrophin (hMG) and subsequent intrauterine insemination were enrolled in the study. Transvaginal ultrasonography (7.0 MHz) was used to determine the total number of antral follicles (2-8 mm) in the right and left ovaries. The association among the antral follicle count, age, dominant follicle, and estradiol (E2) level on the day of human chorionic gonadotropin (hCG) was analyzed. The association of the pregnancy rate and OHSS with the antral follicle count, dominant follicle count, and age was also examined.. The total antral follicle number decreased with age (P < 0.0001). Dominant follicle number increased with total antral follicle number in women who received CC plus hMG/ IUI(P < 0.0001). The pregnant group had a higher number of antral follicle and dominant follicles in comparison with the nonpregnant group (P < 0.01 and P < 0.02, respectively). The E2 level on the day of hCG injection increased positively with the total number of antral follicles (P < 0.0001) and the total number of dominant follicles (P < 0.0001). In women aged younger than 35 years, the pregnancy rate and dominant follicle number rose as the number of antral follicles increased (P < 0.03 and P < 0.0001, respectively). The pregnancy rate was low (2/39) in women aged older than 35 years regardless of the number of antral follicles (P < 0.05) and the extent of hMG administration (P < 0.02). Women aged older than 35 also produced fewer dominant follicles (P < 0.001). No pregnancy was achieved in a patient with an antral follicle number of less than five (17 cases).. Age-related changes in antral follicle count significantly predicted the dominant follicle count and the pregnancy outcome. In women with antral follicle counts of less than five or who are older than 35 years, the application of COH/IUI may not be indicated.

Topics: Age Factors; Cell Count; Chorionic Gonadotropin; Clomiphene; Estradiol; Female; Follicle Stimulating Hormone; Humans; Insemination, Artificial; Menotropins; Ovarian Follicle; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pregnancy; Pregnancy Outcome; Pregnancy Rate; Statistics as Topic

The impact of severity of endometriosis on the outcome of in vitro fertilization (IVF) was analyzed in an uncontrolled, retrospective study in an academic IVF program.. Sixty-one patients with a primary diagnosis of endometriosis undergoing 85 cycles of IVF were included in the study. Patients were divided according to the severity of disease based on the revised American Fertility Society (AFS) classification into groups A (stages I/II, or minimal/ mild) and B (stages III/IV, or moderate/severe). Group A included 32 patients undergoing 45 IVF-embryo transfer (ET) cycles; group B included 29 patients undergoing 40 IVF cycles. Exclusion criteria were age older than 40 years, basal day 3 follicle stimulating hormone (FSH) greater than 20 IU/L, male-factor infertility, assisted hatching, and gamete intrafallopian transfer cases. Stimulation for IVF cycles was standard using pituitary down-regulation with gonadotropin-releasing hormone agonist in a midluteal protocol. Controlled ovarian hyperstimulation (COH) was achieved using a combination of FSH and human menopausal gonadotropin. Outcomes assessed included response to COH and number, maturity, and quality of oocytes retrieved. Fertilization, implantation, and pregnancy rates after IVF-ET were also analyzed.. The response to COH and the number, maturity, and quality of the oocytes was comparable between patients with varying severity of endometriosis. Fertilization rates for oocytes of patients in group B (stages III/IV) were significantly impaired compared to those in group A (stages I/II) (P = 0.004). The rates for implantation, clinical pregnancy, and miscarriage were comparable between the two groups.. The reduced fertilization potential of the oocytes obtained from patients with severe endometriosis in the absence of male-factor infertility suggests an adverse biological impact of the advanced disease on the oocytes. The outcome of IVF-ET, however, is unaffected by increasing severity of endometriosis. This suggests that IVF may compensate for or overcome this reduction in the biological potential of the oocytes associated with severe disease, thus accounting for a comparable outcome irrespective of the severity of endometriosis.

Topics: Adult; Embryo Implantation; Embryo Transfer; Endometriosis; Female; Fertilization in Vitro; Follicle Stimulating Hormone; Humans; Infertility; Menotropins; Oocytes; Outcome Assessment, Health Care; Ovarian Hyperstimulation Syndrome; Pregnancy; Retrospective Studies

The role of intravenous immunoglobulin (IVIG) in the prevention of severe ovarian hyperstimulation syndrome (OHSS) was evaluated.. Ovarian hyperstimulation was induced in eight rabbits using human menopausal gonadotropin/human chorionic gonadotropin (hMG/hCG) after pretreatment with IVIG (IVIG group) or bovine serum albumin (BSA group). Main outcome measures included (1) signs of OHSS, such as the degree of ascites formation and the increase in body weight; and (2) the degree of ovarian stimulation as reflected by serum sex-steroid hormone levels.. A significantly lower ascites response and a tendency toward a decreased change in body weight were observed in the IVIG group compared to the BSA group. Serum estradiol, progesterone, total protein, and ovarian weights were not statistically different between the two groups.. IVIG prevented severe OHSS in a rabbit model, whereas BSA did not. Further studies are justified in an attempt to clarify the role of the immune system and IVIG in the pathophysiology and prevention of severe OHSS.

Topics: Animals; Ascites; Ascitic Fluid; Blood Proteins; Body Weight; Chorionic Gonadotropin; Cytokines; Estradiol; Female; Immunoglobulins; Menotropins; Ovarian Hyperstimulation Syndrome; Progesterone; Rabbits

Isolated acute unilateral pleural effusion has twice been reported as the only symptom of ovarian hyperstimulation syndrome (Kingsland et al, 1989; Jewelewicz and Vande Wiele, 1975). The pathogenesis of this disorder is not fully understood and the presence of an isolated pleural effusion lends support to the role of systemic factors rather than purely the transudation of fluid from grossly enlarged ovaries in the progression of this disease. This article describes a second case of an isolated pleural effusion following in-vitro fertilization and embryo transfer.

Topics: Adult; Buserelin; Embryo Transfer; Female; Fertilization in Vitro; Humans; Infertility, Male; Male; Menotropins; Ovarian Hyperstimulation Syndrome; Pleural Effusion

Cerebrovascular complications are by far the most serious side-effects of ovarian hyperstimulation syndrome. We report a case in which the patient developed cerebral infarction with right sided hemiplegia as a result of severe hyperstimulation syndrome after using a gonadotrophin-releasing hormone agonist for intracytoplasmic sperm injection.

Topics: Adult; Cerebral Infarction; Chorionic Gonadotropin; Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Humans; Menotropins; Microinjections; Ovarian Hyperstimulation Syndrome; Ovulation Induction

The purpose of our study was to determine which of the two drug regimens is more successful in achieving conception in the infertile couple.. One hundred and sixty women with primary infertility were included in this study. Group A, consisted of 102 patients were treated with clomiphene citrate (CC) and human menopausal gonadotrophin (hMG). Group B, consisted of 58 patients were treated with hMG alone.. This retrospective study was performed between April 1993 and March 1996, to compare the pregnancy rates in women using two drug regimens with ultrasound scan and serum E2 to monitor ovulation induction.. The pregnancy rate per patient in Group A was significantly higher than in Group B (46% vs 25.9%) as was the pregnancy rate per treatment cycle (31.3% vs 15.8%) pregnancy loss was lower in Group A than in Group B (17% vs 33.3%). The incidence of multiple pregnancy was 8.5% in Group A, and 13.3% in Group B. While the incidence of ovarian hyperstimulation syndrome was 3% in Group A, and 6.9% in Group B.. We concluded that the use of CC + hMG in an assisted conception programme gives a better pregnancy rate 46% than in the hMG alone 25.9%. These data with the use of U/S scan and serum E2 clearly showed that the use of CC + hMG is a successful and safe method for the treatment of infertile patients.

Topics: Adult; Clomiphene; Drug Therapy, Combination; Estrogens; Female; Fertility; Fertility Agents, Female; Humans; Incidence; Injections, Intravenous; Jordan; Menotropins; Ovarian Hyperstimulation Syndrome; Ovulation; Ovulation Induction; Pregnancy; Pregnancy Rate; Retrospective Studies

The study presented herein evaluated whether 26 of 122 consecutive women who tend to hyper-respond (serum estradiol >4,000 pg/ml or >30 follicles) following controlled ovarian hyperstimulation for in vitro fertilization have higher serum FSH levels at certain critical stages during the follicular phase. Baseline day-2 serum FSH and blood levels taken on days 5 and 6 of human menopausal gonadotropin therapy were not different in the hyper-responders from those responding normally. The only significant difference in serum FSH was seen on the day of human chorionic gonadotropin where it was actually lower in the hyper-responders. Thus, there does not appear to be a critical serum FSH level which would dictate a decrease in gonadotropins to prevent hyper-response.

Topics: Adult; Biomarkers; Chorionic Gonadotropin; Enzyme-Linked Immunosorbent Assay; Estradiol; Female; Fertility Agents, Female; Fertilization in Vitro; Follicle Stimulating Hormone; Humans; Injections, Subcutaneous; Leuprolide; Luteinizing Hormone; Menotropins; Ovarian Follicle; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Risk Factors; Ultrasonography

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

In-vitro fertilization patients (n = 15) at risk of ovarian hyperstimulation syndrome (OHSS) (oestradiol > or =4500 pg/ml on the day of human chorionic gonadotrophin administration and 25 or more follicles of intermediate or large size) underwent aspiration of all follicles and cryopreservation of all fertilized oocytes at the pronuclear stage. Patients were monitored for up to 2 weeks post-retrieval. Subsequent transfer of cryopreserved-thawed embryos was performed in programmed cycles using exogenous oestrogen and progesterone for endometrial preparation. Two patients (13%) developed OHSS necessitating hospitalization and vaginal aspiration of ascitic fluid. Two other patients (13%) developed moderate OHSS requiring ascitic fluid vaginal aspiration in the office setting, with dramatic improvement of the condition. Subsequent transfer of cryopreserved-thawed embryos yielded a clinical pregnancy rate of 58% per transfer and ongoing or delivery rates of 42 and 67% per transfer and per patient respectively. By eliminating pregnancy potential with cryopreservation of all prezygotes and examining the pregnancy potential with subsequent cryopreserved-thawed transfers, it is concluded that OHSS is reduced, but not eliminated for patients at risk. Subsequent transfer of cryopreserved-thawed prezygotes in a programmed cycle with exogenous steroids yields an excellent pregnancy rate.

Topics: Adult; Chorionic Gonadotropin; Cryopreservation; Embryo Transfer; Estradiol; Female; Fertilization in Vitro; Follicle Stimulating Hormone; Hot Temperature; Humans; Infertility, Female; Leuprolide; Menotropins; Ovarian Follicle; Ovarian Hyperstimulation Syndrome; Pregnancy; Risk Factors

We investigated the possible effects of the angiotensin converting enzyme (ACE) inhibitor cilazapril and angiotensin II antagonist saralasin on ovulation, ovarian steroidogenesis and ascites formation in the ovarian hyperstimulation syndrome (OHSS) in the rabbit model. OHSS was induced in rabbits by human menopausal gonadotropin (hMG) and intermittent human chorionic gonadotropin (hCG). In the cilazapril group (n = 10), animals also received cilazapril 2 mg/kg intraperitoneally daily for 7 days. In the saralasin group (n = 8), animals received saralasin intraperitoneally 1 h before or 1 h after hCG administration. Control animals (n = 8), received intraperitoneal saline solution. Serial blood samples were drawn on days 1, 5, 7 and 9 to measure serum estradiol and progesterone levels. On day 9, all rabbits underwent surgical exploration. Peritoneal and pleural fluid formation, ovarian weights and number of ovulations were determined. The volume of the ascitic and pleural fluids after hyperstimulation were not statistically different between the control, cilazapril and saralasin groups. The weight gains and ovarian weights of animals were similar between treatment and control groups. Saralasin significantly (p < 0.05) inhibited ovulation, but cilazapril did not. Cilazapril and saralasin did not affect progesterone production. Only cilazapril significantly decreased estradiol production (p < 0.05). In conclusion, the ACE inhibitor cilazapril and angiotensin II antagonist saralasin did not prevent ascites formation in OHSS. The ovarian renin-angiotensin system may not be the only factor acting in ascites formation in the OHSS.

Topics: Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Animals; Ascitic Fluid; Body Weight; Chorionic Gonadotropin; Cilazapril; Estradiol; Female; Menotropins; Ovarian Hyperstimulation Syndrome; Ovulation; Progesterone; Rabbits; Saralasin

Ascites is a clinical manifestation of severe ovarian hyperstimulation syndrome (OHSS) which may complicate the induction of ovulation using exogenous gonadotrophins. In severe OHSS severe ascites may occur and can lead to dyspnoea, abdominal discomfort and oliguria. To relieve ascites paracentesis is performed two to three times weekly as needed. We report three cases where an indwelling peritoneal catheter was used to decrease the need for repeated paracentesis. Under ultrasound guidance a closed system Dawson-Mueller catheter with 'simp-loc' locking design was inserted to allow continuous drainage of the ascitic fluid. A total of 23 l of the ascitic fluid were drained from the first, 20 l from the second and 28 l from the third patient with significant decrease in abdominal discomfort and improvement in the urine output. No complications or adverse reactions were noted. Continuous drainage of the ascitic fluid is efficient. It quickly decreases the abdominal discomfort, improves the urine output and prevents the need for multiple abdominal paracenteses which some patients may require.

Topics: Adult; Ascites; Catheters, Indwelling; Chorionic Gonadotropin; Drainage; Embryo Transfer; Female; Fertilization in Vitro; Humans; Menotropins; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Paracentesis; Peritoneal Cavity

Direct intraperitoneal insemination (DIPI) is one of the least invasive strategies of assisted reproduction. Unexplained infertility, cervical factors and male sub-fertility are major indications for DIPI. This is a report of pregnancy that occurred as a result of a novel trial of DIPI, in which ovarian stimulation took place using a long gonadotropin-releasing hormone (GnRH) analogue and human menopausal gonadotropin (HMG) protocol in a patient who had been unsuccessfully treated with intrauterine insemination.

Topics: Adult; Buserelin; Female; Fertility Agents, Female; Gonadotropin-Releasing Hormone; Humans; Infertility, Female; Insemination, Artificial, Homologous; Male; Menotropins; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pregnancy; Superovulation; Treatment Outcome

Ovarian stimulation is used to treat female infertility, especially in Black Africa where infertility is considered as shameful. Ovarian stimulation can lead not only to multiple pregnancies but also to severe systemic complications such as the one described in this report. Ovarian stimulation using human menopausal gonadotropin led to ovarian hyperstimulation and multiple organ failure in a 28-year-old Senegalese woman. Symptomatic treatment using corticosteroids, abdominal paracentesis to relieve ascites, and fluid expansion failed. Bilateral ovariectomy was performed resulting in permanent sterility. Ovarian stimulation requires close monitoring by ultrasound visualization and measurement of 17 beta-estradiol to allow early detection of complications.

Topics: Adrenal Cortex Hormones; Adult; Ascites; Drug Monitoring; Estradiol; Female; Fertility Agents, Female; Fluid Therapy; Humans; Infertility, Female; Menotropins; Multiple Organ Failure; Ovarian Hyperstimulation Syndrome; Ovariectomy; Ovulation Induction; Paracentesis

To examine the production and immunolocalization of interleukin-6 (IL-6) in patients with the ovarian hyperstimulation syndrome.. The study group consisted of patients with ovarian hyperstimulation syndrome (n = 9) from whom serum and ascites samples were obtained. The control samples used were serum (n = 10) and peritoneal (n = 16) and follicular fluids (n = 8) from healthy individuals. Follicular fluid (n = 40) and serial serum samples were also obtained from patients undergoing menotropin stimulation for in vitro fertilization (IVF) before (n = 10) and after ovulation (n = 34). Interleukin-6 measurements were performed with a sensitive immunoassay and confirmed with a bioassay. Immunohistochemical localization of IL-6 was performed with a mouse monoclonal antibody in normal premenopausal (n = 5) and postmenopausal ovaries (n = 5), as well as with cells from stimulated follicular fluid aspirates (n = 3).. We found significantly higher serum and ascites IL-6 levels in ovarian hyperstimulation syndrome (mean 18.8 +/- 1.1 and 810.8 +/- 60.7 pg/mL, respectively) compared with postovulatory serum and peritoneal fluid from normal controls (mean 4.4 +/- .69 and 44.7 +/- 7.5 pg/mL, respectively) (P < .001) or serum after menotropin stimulation (13.1 +/- 1.1 pg/mL) (P < .001). At the time of ovulation, follicular fluid IL-6 levels (normal controls, mean 9 +/- 2.1 pg/mL; menotropin stimulation, mean 10.1 +/- 4 pg/mL) were higher than in preovulatory serum (normal controls, mean 4.5 +/- .8 pg/mL; menotropin stimulation, mean 6.3 +/- 1.4 pg/mL) (P < .001). Immunohistochemical localization of IL-6 revealed intense staining in corpora lutea and theca cells from large antral follicles and luteinized granulosa cells in follicular aspirates after menotropin stimulation.. Interleukin-6 levels are markedly elevated in the ovarian hyperstimulation syndrome when compared with controls. The higher follicular fluid IL-6 levels seen suggest local secretion of this cytokine. Immunohistochemical correlation demonstrated IL-6 within ovarian theca cells. These findings suggest a local role for IL-6 both in normal and stimulated ovarian function. Whether IL-6 is directly responsible for the clinical manifestations of this syndrome is unclear. However, when produced in massive amounts, the pro-inflammatory effects of IL-6 may contribute to its pathogenesis and perhaps serve as a marker for the disease.

Topics: Adult; Animals; Ascitic Fluid; Biological Assay; Female; Humans; Immunoassay; Immunohistochemistry; Interleukin-6; Menotropins; Mice; Ovarian Hyperstimulation Syndrome

The case of an arterial aorto-subclavian thromboembolism associated with a moderate ovarian hyperstimulation syndrome (OHSS) and following ovulation induction for in-vitro fertilization in a young woman is reported. Because of the lack of response to systemic thrombolysis, a left postero-lateral thoracotomy was performed on day 8 after embryo transfer. A fibrinocruoric embolus situated at the junction of the left subclavian artery from the aorta was removed through a left subclavian arteriotomy. The distal axillary embolus was removed by a retrograde balloon catheter embolectomy. A moderate OHSS was observed. The ovarian stimulation and OHSS-related risks of thromboembolism are discussed. We conclude that, in the absence of risk factors, counselling about possible complications resulting from stimulation must be emphasized.

Topics: Adult; Aorta; Chorionic Gonadotropin; Female; Gonadotropin-Releasing Hormone; Humans; Menotropins; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Subclavian Artery; Thromboembolism; Triptorelin Pamoate

Ovarian hyperstimulation syndrome (OHSS) is the most serious, life-threatening, iatrogenic complication of ovulation induction. The importance of excessive oestradiol concentrations on the day of human chorionic gonadotrophin (HCG) administration as a predictor and factor in the pathophysiology of OHSS has been extensively studied and discussed. We present the case report of a woman with hypogonadotrophic hypogonadism who developed severe OHSS during ovulation induction with urinary human follicle stimulating hormone (FSH) and HCG in the presence of low circulating oestradiol concentrations. The implication of FSH treatment and complications in hypogonadotrophic hypogonadal patients, and the role of preovulatory oestradiol concentrations in the prediction of OHSS, are discussed.

Topics: Adult; Chorionic Gonadotropin; Craniopharyngioma; Estrogens; Female; Humans; Hypogonadism; Menotropins; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pituitary Neoplasms

To determine the effectiveness of human menopausal gonadotropin (hMG) with intrauterine insemination (IUI) for the treatment of various causes of infertility and to identify prognostic factors for the success of this treatment.. Retrospective chart analysis.. Of the 271 cycles initiated, 247 were completed in 104 couples, and analysis of these cycles showed that the overall cycle fecundity rate was 10% and the pregnancy rate 22%. The miscarriage rate was 8% and the ectopic pregnancy rate 4%. The multiple pregnancy rate was 29%. For the various causes of infertility, we found that the cycle fecundity rate was 7% for male factor, 11% for oligoovulation, 8% for tubal/pelvic factor, 13% for minimal endometriosis, 18% for mild endometriosis, 17% for moderate endometriosis, 3% for women aged > or = 40 years, 75% for myoma, and 7% for idiopathic infertility. We also found that one IUI timed at 36-48 hours was as effective as two IUIs timed at 18-24 and 36-48 hours after human chorionic gonadotropin (hCG) administration. Poor prognostic factors that were elicited from this study were: (1) failure of pregnancy in three cycles of treatment, (2) female age > or = 40 years, (3) requirement of > 300 IU of hMG daily, and (4) presence of more than eight mature follicles at the time of hCG administration.. HMC and IUI are effective treatment of some causes of infertility.

Topics: Adult; Combined Modality Therapy; Estrogens; Female; Fertility Agents, Female; Humans; Infertility, Female; Insemination, Artificial; Male; Menotropins; Middle Aged; Ovarian Hyperstimulation Syndrome; Pregnancy; Pregnancy Outcome; Prognosis; Retrospective Studies; Time Factors

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 total of 32 patients undergoing in vitro fertilization (IVF) and 16 treated for ovulatory disturbances were stimulated with clomiphene citrate and human menopausal gonadotropin. Gonadotropin releasing hormone (GnRH) analog was used for induction of the ovulatory surge of gonadotropins, because of the risk of ovarian hyperstimulation syndrome. In four patients after IVF-embryo transfer and four patients after ovulation induction, single pregnancies were obtained. None suffered from ovarian hyperstimulation syndrome. The authors suggest that the use of GnRH analog for induction of the gonadotropin ovulatory surge prevents the development of ovarian hyperstimulation syndrome.

Topics: Buserelin; Chorionic Gonadotropin; Clomiphene; Embryo Transfer; Estradiol; Female; Fertility Agents, Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Gonadotropins; Humans; Menotropins; Ovarian Hyperstimulation Syndrome; Ovary; Ovulation Induction; Pregnancy; Pregnancy Rate; Progesterone; Risk Factors

To report an unexpected case of severe ovarian hyperstimulation syndrome (OHSS) and to compare E2 levels and number of follicles to other oocyte donors.. Private assisted reproduction technology center.. Healthy oocyte donors with normal menstrual cyclicity.. Prophylactic and therapeutic use of human serum albumin infusions.. The clinical development of signs and symptoms of severe OHSS.. More than 60% of other oocyte donors had higher E2 levels and 12% had higher number of follicles without associated OHSS.. The risk of developing severe OHSS cannot be predicted accurately to be low even in the absence of "risk factors."

Topics: Adult; Female; Forecasting; Humans; Menotropins; Oocyte Donation; Ovarian Hyperstimulation Syndrome; Serum Albumin

To describe a patient with severe ovarian hyperstimulation syndrome (OHSS) demonstrating a beneficial result of reduction in abdominal ascites with a chest tube placed for bilateral pleural effusions.. Case report.. Academic hospital.. A 28-year-old white female with primary infertility on hMG (Pergonal; Serono Laboratories, Randolph, MA) therapy.. Intravenous fluids, lasix, and albumin were administered for correction of laboratory abnormalities, including hemoconcentration, hypoalbuminemia, and leukocytosis. A chest tube was placed for treatment of pleural effusions.. Laboratory values of hematologic measures and electrolytes. Resolution of pleural effusions and abdominal ascites as determined by chest roentgenogram and physical examination.. Treatment of OHSS with intravenous fluids, lasix, and albumin corrected the hemoconcentration, hypoalbuminemia, and leukocytosis associated with OHSS. Placement of a chest tube corrected the pleural effusions and abdominal ascites.. This case report demonstrates a beneficial result of reduction in abdominal ascites by a chest tube placed for pleural effusions.

Topics: Adult; Ascites; Chest Tubes; Drainage; Female; Fluid Therapy; Humans; Infertility, Female; Menotropins; Ovarian Hyperstimulation Syndrome; Pleural Effusion

In 3,972 human menopausal gonadotropin (hMG) and human chorionic gonadotropin (hCG)-stimulated menstrual cycles, severe ovarian hyperstimulation syndrome (SOHSS) developed in 10 patients (0.25%), while in 627 hMG-, hCG- and gonadotropin releasing hormone analog (GnRH-a)-stimulated cycles, 6 patients (0.95%) developed SOHSS. In cases of threatening SOHSS in the follicular phase (excessive estradiol values, multiple follicles), a preventive method was applied: follicular aspiration 12 hours after hCG administration and regular oocyte retrieval 36 hours after hCG (17 patients). The method of post-hCG aspiration in one ovary was effective, leading to the withdrawal of all signs of SOHSS within six days after the second aspiration. In hMG-stimulated, pretreated patients there were four deliveries of seven healthy infants (two singleton, one twin and one triplet), while one pregnancy in seven GnRH-a-stimulated and pretreated patients ended in a spontaneous abortion. Post-hCG aspiration is a quick, simple and effective method that prevents the development of SOHSS and permits pregnancy in the treated cycle. Although the pregnancy rate in patients who developed SOHSS was higher (100% per embryo transfer), one should also consider the high spontaneous abortion rate (33.3% for the hMG- and 50% for the GnRH-a/hMG-treated groups) and the fact that SOHSS is a life-threatening condition, demanding expensive, intensive care. According to our experience, post-hCG follicular aspiration is the treatment of choice in patients with signs of SOHSS.

Topics: Chorionic Gonadotropin; Embryo Transfer; Female; Fertilization in Vitro; Humans; Menotropins; Ovarian Follicle; Ovarian Hyperstimulation Syndrome; Pregnancy; Pregnancy Outcome; Suction

Cases of coexisting ovarian hyperstimulation and ectopic pregnancy are rare, and pose a difficult diagnostic problem. The routine attempts at laparoscopic diagnosis and treatment of these pregnancies may prove to be hazardous. Such cases may be better managed nonsurgically either by methotrexate or, in selected cases, by expectant management while monitoring the beta-hCG level and clinical status.

Topics: Adult; Chorionic Gonadotropin; Clomiphene; Female; Humans; Infertility, Female; Insemination, Artificial, Homologous; Menotropins; Ovarian Cysts; Ovarian Hyperstimulation Syndrome; Pregnancy; Pregnancy, Ectopic; Ultrasonography

Topics: Adult; Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Humans; Menotropins; Ovarian Hyperstimulation Syndrome; Pregnancy; Pregnancy Outcome

A recently identified cytokine, vascular endothelial growth factor (VEGF, vascular permeability factor) has been implicated in ovarian hyperstimulation syndrome in women undergoing assisted reproduction. We postulate that circulating and urinary VEGF values increase following gonadotrophin stimulation, in parallel with the increased ovarian vascularity. A VEGF radioimmunoassay was developed using iodinated VEGF as tracer, a goat anti-VEGF serum as antiserum and recombinant human VEGF as standard. The specificity of the assay was confirmed by comparing the reverse phase high-performance liquid chromatography (HPLC) pattern of VEGF immunoactivity in urine and urine spiked with recombinant VEGF. Urine was concentrated 5-fold prior to measurement by the radioimmunoassay. VEGF:creatinine ratios in early morning urine samples were used to monitor daily urinary VEGF concentrations based on its high correlation (r = 0.77, P < 0.001) with VEGF concentrations in 24 h urine collections. No diurnal variation in VEGF:creatinine ratios was detected. VEGF:creatinine ratios were determined daily from nine women undergoing gonadotrophin-releasing hormone (GnRH) agonist/gonadotrophin treatment. In a further 16 women, early morning urine samples were collected in the peri-ovulatory period. A significant increase (P < 0.005, n = 25) was observed in VEGF:creatinine ratios following human chorionic gonadotrophin (HCG) administration. VEGF:creatinine ratios correlated poorly (r < 0.34) with plasma oestradiol, follicle number and size. It is concluded that urinary VEGF/creatinine ratios increase following HCG stimulation.

Topics: Chorionic Gonadotropin; Chromatography, High Pressure Liquid; Circadian Rhythm; Endothelial Growth Factors; Female; Fertilization in Vitro; Humans; Leuprolide; Lymphokines; Menotropins; Ovarian Hyperstimulation Syndrome; Pregnancy; Radioimmunoassay; Recombinant Proteins; Sensitivity and Specificity; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors

Exogenous estradiol (E2) has a well-recognized interceptive action when administered shortly after ovulation. The influence of extremely elevated levels of endogenous E2 on human oocyte fertilization and implantation are unclear. The purpose of this study was to evaluate a potential antinidatory role of extremely high endogenous E2 concentrations on implantation and pregnancy during in vitro fertilization-embryo transfer (IVF-ET).. Twenty-five patients receiving human menopausal gonadotropins (hMG) following midluteal GnRHa administration for IVF-ET, in which the maximal E2 concentration was > 5000 pg/ml (range 5358-16,344 pg/ml) were studied. Cycle parameters including oocyte and embryo characteristics, fertilization, cleavage, and implantation rates as well as pregnancy outcomes were compared to those of 25 patients treated contemporaneously whose treatment cycles had peak E2 values < 3500 pg/ml. Patients groups were matched for age, infertility diagnoses, duration of infertility and stimulation protocol.. Cycles characterized by very high endogenous E2 levels resulted in significantly more oocytes per retrieval (21.4 +/- 1.7 versus 8.4 +/- 0.6; P < 0.0001), fewer postmature oocytes (1.6% +/- 1.0% versus 14% +/- 5.0%; P < 0.03), and a decreased fertilization rate (63% +/- 4.0% versus 73% +/- 3.0%; P < 0.04) compared to control cycles. There were no differences in the overall mean morphologic grade or cleavage rates between groups. However, high E2 cycles were associated with a significantly increased implantation rate (14% +/- 4.0% versus 8.0% +/- 4.0%; P < 0.01) and pregnancy rate per embryo transfer (62% +/- 16% versus 36% +/- 16%; P < 0.01) compared to controls. The incidence of spontaneous abortion did not differ between groups. CONCLUSIONS; Extremely high endogenous E2 levels do not appear to adversely affect implantation or overall cycle pregnancy rates in IVF-ET cycles. However, impaired fertilization rates in such cycles support a potential adverse effect on oocyte quality.

Topics: Adult; Embryo Implantation; Embryo Transfer; Endometriosis; Estradiol; Female; Fertility Agents, Female; Fertilization in Vitro; Humans; Infertility, Female; Menotropins; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pregnancy; Radioimmunoassay

Over a 4 year period ending 1 January 1995, 51 women scheduled for in-vitro fertilization (IVF) and embryo transfer were inadvertently severely overstimulated with menotrophins, as evidenced by the development of > 29 ovarian follicles in association with peak plasma oestradiol concentrations of > 6000 pg/ml. Accordingly, these women were at great risk of developing life-endangering complications associated with severe ovarian hyperstimulation syndrome (OHSS). Treatment involved withholding the administration of both menotrophins and human chorionic gonadotrophin for a number of days, while continuing gonadotrophin-releasing hormone agonist until the plasma oestradiol concentration fell to < 3000 pg/ml ('prolonged coasting'). The mean number of oocytes retrieved was 21.0, while the mean number of embryos transferred per procedure was 5.4. There were 21 clinical pregnancies (i.e. pregnancy rate of 41% per oocyte retrieval), 19 of which resulted in live births (i.e. a live birth rate of 37% per oocyte retrieval). Two pregnancies miscarried and there were four multiple gestations (three sets of twins and one set of triplets). None of the women developed severe OHSS. Prolonged coasting is an effective method of preventing the occurrence of severe OHSS without necessitating the cancellation of the IVF cycle or compromising success rates.

Topics: Adult; Chorionic Gonadotropin; Embryo Transfer; Estradiol; Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Granulosa Cells; Humans; Menotropins; Oocytes; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pregnancy; Pregnancy Outcome; Pregnancy, Multiple; Risk Factors

A case of advanced ectopic pregnancy after in vitro fertilization complicated by an ovarian hyperstimulation syndrome is presented. Methotrexate was given in spite of high levels of hCG and appeared to be successful. Difficulties in the choice between surgical and conservative treatment are discussed.

Topics: Adult; Embryo Transfer; Fallopian Tubes; Female; Fertilization in Vitro; Humans; Infertility, Female; Menotropins; Methotrexate; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pregnancy; Pregnancy, Ectopic; Tissue Adhesions

Cerebral infarction due to menotropin therapy without evidence of ovarian hyperstimulation is presented. The patient was successfully treated with aspirin and anticonvulsive agents and was discharged without residual neurologic symptoms.

Topics: Adult; Cerebrovascular Disorders; Clomiphene; Female; Humans; Menotropins; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Tomography, X-Ray Computed

Thirty patients with OHS were analyzed; all of them had to be hospitalized. There was no difference as to sterility time and syndrome appearance. The use of menotropines caused more frequently the syndrome. There was multiple pregnancy in 33%. Abortion incidence was 16%. As the etiology is unknown there is not an adequate treatment, and care is for maintenance. Prevention is the best option.

Topics: Adult; Clomiphene; Female; Follicle Stimulating Hormone; Hospitalization; Humans; Menotropins; Mexico; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pregnancy; Retrospective Studies

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

In an attempt to evaluate the risks and benefits of human menopausal gonadotrophin (hMG) therapy for patients with unexplained infertility, the response and outcome of hMG therapy for anovulatory patients and ovulatory patients with unexplained infertility were analyzed in a group of successful cases of pregnancy. The number of follicles grown and the total doses of hMG were not significantly different in the two groups. The rate of spontaneous abortion in unexplained cases was twice as high (13.2%) as in anovulatory cases. However, the rate of multiple pregnancy was 8.8% for unexplained cases which was significantly lower than that for anovulatory cases (39.0%). In addition, ovarian hyperstimulation syndrome (OHSS) occurred in 11.8% of unexplained cases and that was much lower than that for anovulatory cases (25.8%). This study justifies the application of gonadotrophin therapy to ovulatory patients with unexplained infertility in terms of the risks and benefits of the therapy in achieving pregnancy.

Topics: Adult; Female; Humans; Infertility, Female; Menotropins; Ovarian Hyperstimulation Syndrome; Ovulation; Ovulation Induction; Prognosis; Risk; Treatment Outcome

The incidence of ovarian hyperstimulation syndrome (OHSS) is directly correlated with the pre-human chorionic gonadotropin blood estrogen (E) levels. The higher the E content, the greater the chances of OHSS. However, even when the E levels are very high, only 2.96% of the patients developed severe OHSS. Younger women with primary ovarian dysfunction are more at risk than older women. Human chorionic gonadotropin should be withheld when the estradiol levels are over 4,000 pg/ml; however, the patients should be individualized, since some patients--particularly older women--may require higher blood estradiol levels for successful ovulation induction.

Topics: Age Factors; Chorionic Gonadotropin; Estradiol; Female; Humans; Menotropins; Ovarian Hyperstimulation Syndrome; Pregnancy; Retrospective Studies; Risk Factors

This is a report on the institutional experience of the use of Human Menopausal Gonadotropins (HMG) in anovulatory women diagnosed as hypothalamic-hypophysiary dysfunction of Group II of WHO with previous failure to chlomifen citrate therapy. In a period of three years 180 patients were gathered with 420 cycle of treatment, obtaining ovulation in 340 cycles (81%). The ovarian hyperstimulation syndrome (OHS) was present in 15 cases (3.5%). There were 115 pregnancies that correspond to 33.8% of oculatory cycles and to 63.8% of the amount of patients. Multiple pregnancy incidence was 10.4%, and the gestational loses rate was 26%; these results are similar to what has been reported in literature. It is concluded that this medication is a good option of treatment for this type of patients, provided that there are the necessary means to expert and adequate surveillance.

Topics: Adult; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Humans; Hypothalamo-Hypophyseal System; Menotropins; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pregnancy; Treatment Outcome; World Health Organization

Seventy-five patients with a total of 306 human menopausal gonadotropin treatment cycles over the period 1984-1989 were analysed retrospectively to evaluate the value of transabdominal pelvic ultrasonography in prevention of complications arising from ovulation induction with human menopausal gonadotropins. There were 60 pregnancies giving a pregnancy rate of 19.6% per cycle. There was positive correlation between the number of follicles > or = 14 mm in mean diameter and the incidence and degree of hyperstimulation (p < 0.005) as well as the incidence of multiple pregnancies (p < 0.01). Ultrasonography is a useful adjunct for monitoring in such a program.

Topics: Adult; Female; Humans; Menotropins; Monitoring, Physiologic; Ovarian Hyperstimulation Syndrome; Ovary; Ovulation Induction; Pregnancy; Pregnancy, Multiple; Retrospective Studies; Ultrasonography

Topics: Chorionic Gonadotropin; Embryo Transfer; Estradiol; Female; Fertilization in Vitro; Humans; Menotropins; Oocytes; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Predictive Value of Tests; Pregnancy; Pregnancy Outcome; Prognosis; Treatment Outcome

A retrospective analysis of ovarian hyperstimulation syndrome in high responders undergoing in-vitro fertilization (IVF) is presented. High responders were defined as having > 20 follicles and serum oestradiol > 3000 pg/ml after treatment with human menopausal gonadotrophin. Of the initial 30 IVF cycles in high responders, 23 developed a moderate-to-severe ovarian hyperstimulation syndrome (76.7%). Subsequently, 15 other IVF cycles in high responders were combined with a repeated aspiration of ovarian follicles and corpus luteum cysts just prior to embryo transfer. Only three patients (20%) developed a moderate ovarian hyperstimulation syndrome (P = 0.0004). We conclude that repeated follicular aspiration is safe and results in a significant reduction in the incidence and severity of this condition in high responders undergoing IVF.

Topics: Adult; Chorionic Gonadotropin; Corpus Luteum; Estradiol; Female; Fertilization in Vitro; Humans; Menotropins; Ovarian Follicle; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Risk Factors; Suction

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

To evaluate a new method for preventing the life-endangering complications associated with inadvertent menotropin-induced severe ovarian hyperstimulation in patients undergoing in vitro fertilization and embryo transfer (IVF-ET).. Seventeen women each underwent a single cycle of controlled ovarian hyperstimulation with menotropins in preparation for IVF-ET. The indications for IVF-ET were tubal occlusion in nine, endometriosis in six, and unexplained infertility in two. The peak plasma estradiol (E2) concentration before hCG administration was greater than 6000 pg/mL and more than 30 ovarian follicles were detected by transvaginal ultrasound. Thus, life-endangering complications associated with severe ovarian hyperstimulation syndrome were highly likely to occur following hCG administration. Rather than cancel the cycle of treatment, menotropin therapy was discontinued and hCG administration was deferred for a number of days until the plasma E2 concentration fell below 3000 pg/mL ("prolonged coasting"), whereupon hCG was administered and egg retrievals and ETs were duly performed.. None of the women developed severe ovarian hyperstimulation syndrome. There were six viable pregnancies (35.2%), which proceeded normally.. This study indicates that "prolonged coasting" prevents severe ovarian hyperstimulation syndrome in severely overstimulated women undergoing IVF-ET, without necessitating cycle cancellation.

Topics: Adult; Chorionic Gonadotropin; Drug Administration Schedule; Embryo Transfer; Estradiol; Female; Fertilization in Vitro; Follicle Stimulating Hormone; Humans; Leuprolide; Menotropins; Ovarian Hyperstimulation Syndrome; Time Factors

Topics: Adult; Chorionic Gonadotropin; Diuretics; Female; Furosemide; Humans; Menotropins; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pregnancy

A total of 28 women scheduled for in-vitro fertilization used buserelin and human menopausal gonadotrophin (HMG) for ovarian stimulation. One group (I) of 17 women was given human chorionic gonadotrophin (HCG 10,000 IU) to trigger ovulation, but the resulting embryos were electively cryopreserved because of the risk (serum oestradiol greater than or equal to 3500 pg/ml) of developing the ovarian hyperstimulation syndrome (OHSS). Six women continued the buserelin therapy in the luteal phase and eleven did not. In group II (n = 11), the HMG injections were discontinued because of an exaggerated ovarian response and the HCG was omitted. Six of these women continued the buserelin injections until the onset of menses and five did not. In both groups, the ovarian response to induction of ovulation (serum oestradiol concentrations and number of follicles) was similar for those who did or did not continue buserelin therapy. There was no difference in the rate of ovarian quiescence (weekly fall in serum oestradiol concentration following the stimulation) between those women who did or did not continue the buserelin therapy in either group. The serum luteinizing hormone concentrations remained low in all women in both groups. We conclude that the omission of buserelin therapy after discontinuing the HMG in women at risk of developing OHSS does not affect subsequent ovarian quiescence.

Topics: Adult; Buserelin; Chorionic Gonadotropin; Estradiol; Female; Fertilization in Vitro; Humans; Luteinizing Hormone; Menotropins; Ovarian Hyperstimulation Syndrome; Ovulation Induction

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

The purpose of this study was to evaluate the influence of the relationship between plasma progesterone (P4) and estradiol (E2) levels in the luteal phase for achieving pregnancy in human menopausal gonadotropin (hMG)-human chorionic gonadotropin (hCG)-treated cycles. Plasma P4 and E2 levels were determined in 93 hMG-hCG-treated cycles (23 pregnant and 70 nonpregnant) of 46 patients during 3 periods of the luteal phase, using radioimmunoassay. In addition, 88 spontaneous ovulatory cycles and 100 clomiphene-treated cycles were also studied in the same manner. In hMG-hCG-treated cycles in the early luteal phase, the P4/E2 ratio in pregnant cycles was significantly higher than that in nonpregnant cycles. There was no significant difference between the P4/E2 ratios of the luteal phase of hMG-hCG-treated pregnant-group, clomiphene-treated and spontaneous ovulatory cycles. In nonpregnant cycles, however, the P4/E2 ratio in hMG-hCG-treated cycles was significantly lower than that in clomiphene-treated or spontaneous ovulatory cycles. These results suggest that in hMG-hCG-treated cycles, the P4/E2 ratio may be a more reliable index of luteal function for achieving pregnancy than P4 levels alone.

Topics: Chorionic Gonadotropin; Clomiphene; Corpus Luteum; Estradiol; Female; Humans; Infertility, Female; Menotropins; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pregnancy; Progesterone; Radioimmunoassay

Frequency and features of ovarian hyperstimulation syndrome (OHS) were reviewed in 41 women stimulated with human menopausal gonadotropin (HMG) during 130 cycles. There were 7 cases of OHS, since 17% of patients and 5.3% of cycles were affected; 3 cases were mild, 2 moderate and 2 severe. Of these 41 women, 21 pregnancies occurred (51%) and 19 newborns were healthy. The patients with OHS received 1060 +/- 235 (X +/- DE) UI of HMG and there was not a significative difference with the amount of HMG units in remaining subjects. Symptoms began 3-6 days after human chorionic gonadotropin (HCG) administration. Women with mild OHS were treated as out patients with bed rest and 100 mg indomethacin in suppositories two times a day. Moderate and severe OHS were hospitalized with bed rest; careful monitoring of fluid intake and output, weight and abdominal perimeter daily, as well as vital signs were withdrawn. Patients with severe OHS were treated in the intensive care unit for detection and management of complications. One patient was submitted to laparotomy because of a probably ovarian rupture, but it was discarded in the surgery. OHS remained between 6 and 8 days. Patients with OHS presented 3 pregnancies, 2 were twins and the other was ectopic. Emphasis was made in the prophylactic measures to avoid the OHS.

Topics: Adult; Female; Humans; Menotropins; Ovarian Hyperstimulation Syndrome

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

To investigate the relationship between endogenous serum levels of human growth hormone (hGH) and ovarian response to human menopausal gonadotropins (hMG).. Retrospective analysis of patient response to hMG.. Center for assisted reproductive technology.. Eighty women who had undergone controlled ovarian hyperstimulation with hMG. Basal levels of hGH in sera from 40 of these patients were less than 5.0 microIU/mL (low hGH), values for the remaining 40 were greater than 5.0 microIU/mL (high hGH). Levels of hGH in day 2 sera were analyzed against numbers of oocytes recovered in an additional 182 patients.. Serum estradiol (E2) levels and numbers of oocytes recovered at oocyte pick-up.. Average (+/- SE) levels of hGH in sera of high-hGH and low-hGH patients were 10.2 +/- 0.6 and 2.47 +/- 0.3 microIU/mL, respectively (P less than 0.05). Respective peripheral levels of insulin-like growth factor-I were 105.3 +/- 2.9 and 97.2 +/- 2.8 ng/mL. Levels of E2 in serum of high-hGH patients exceeded respective (P less than 0.05) low-hGH values throughout folliculogenesis, and more oocytes were recovered from high-hGH patients (8.1 +/- 0.9 versus 4.7 +/- 0.5 for low-hGH patients; P less than 0.05). Serum progesterone values did not differ. Higher day 2 hGH levels were associated with higher numbers of oocytes recovered after controlled ovarian hyperstimulation.. The present findings indicate that endogenous hGH may augment gonadotropins during follicle recruitment and during multiple folliculogenesis in women. The phase of maximum ovarian sensitivity to hGH/gonadotropin synergism and the nature of synergism remain unclear.

Topics: Adult; Estradiol; Female; Growth Hormone; Humans; Insulin-Like Growth Factor I; Luteal Phase; Menotropins; Ovarian Hyperstimulation Syndrome; Ovary; Progesterone; Retrospective Studies

Initial hope that ovarian hyperstimulation syndrome (OHSS) would be less likely to occur after pituitary suppression with gonadotropin releasing-hormone agonists (GnRH-a) has not been substantiated. GnRH-a/human menopausal gonadotropin (hMG) protocols often lead to OHSS with markedly elevated circulating estradiol (E2) levels in susceptible patients. This study was undertaken to determine whether or not intrafollicular E2 secretion is increased in these cases. Fifty-two in vitro fertilization (IVF) and gamete intrafallopian transfer (GIFT) conception cycles treated with GnRH-a/hMG were included in the study. GnRH-a, leuprolide, 0.5 mg, was administered subcutaneously from day 20 of the preceding cycle and the ovaries were stimulated with hMG, 75-225 IU bid intramuscularly, followed by human chorionic gonadotropin (hCG), 5000 IU. Twenty cycles (Group I) were associated with moderate or severe OHSS and 32 cycles (Group II) did not result in OHSS. E2 was measured in the serum on the day of hCG (day 0), on the day of oocyte retrieval (day 2), and at midluteal phase (days 6-8), as well as in the follicular fluid (FF) using a solid-phase direct RIA. Mean serum E2 was significantly higher at all three sampling times in Group I (OHSS) than in Group II. Both the number of follicles and the number of oocytes were also significantly higher in Group I.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Chorionic Gonadotropin; Estradiol; Female; Fertilization in Vitro; Follicular Fluid; Gamete Intrafallopian Transfer; Gonadotropin-Releasing Hormone; Humans; Injections, Subcutaneous; Leuprolide; Menotropins; Ovarian Hyperstimulation Syndrome; Pituitary Gland

To report a preliminary study on the efficacy of a gonadotropin-releasing hormone antagonist (Nal-Glu) for preventing premature luteinizing hormone (LH) and progesterone (P) rise in controlled ovarian hyperstimulation using clomiphene citrate (CC) and human menopausal gonadotropin (hMG).. Participants in the study formed two groups. Both groups received CC-hMG and Nal-Glu. Group II differs from group I for receiving human chorionic gonadotropin (hCG) and blood samples for 10 days after the second Nal-Glu injection.. Centre de Fecondation in Vitro, Hôpital Antoine Béclère.. Eleven women 25 to 34 years of age and having normal menstrual cycles using barrier method of contraception not attempting pregnancies participated in the study.. Daily blood samples, pelvic ultrasound, and CC-hMG/Nal-Glu/hCG administration.. (1) Spontaneous LH surge and P rise, follicular growth, and plasma E2 levels in cycles with CC-hMG/Nal-Glu administration and (2) luteal phase after hCG injection in subjects previously treated with CC-hMG/Nal-Glu.. Plasma E2 level increased from 983 +/- 80 pg/mL (mean +/- SEM) on the day of the first Nal-Glu administration to 1,159 +/- 102 and 1,610 +/- 114 pg/mL (mean +/- SEM) 24 and 48 hours later. In 10 women, LH and P remained low for at least 96 hours after the first Nal-Glu administration. In one subject, plasma LH was already elevated at the time of the first Nal-Glu injection. In women who received hCG, plasma E2 and P reached a maximum of 1,258 +/- 313 pg/mL and 50.3 +/- 12.8 ng/mL (mean +/- SEM), respectively, on the 6th day of the luteal phase.. Our results suggest that timely Nal-Glu injections can prevent LH and P rise for at least 96 hours, in spite of increasing levels of plasma E2. Moreover, Nal-Glu had no adverse effect on the kinetic of E2 rise, the follicular growth, or on the post-hCG hormonal profile.

Topics: Adult; Estradiol; Female; Gonadotropin-Releasing Hormone; Humans; Luteinizing Hormone; Menotropins; Menstruation; Ovarian Follicle; Ovarian Hyperstimulation Syndrome; Progesterone; Time Factors

Ovarian hyperstimulation syndrome is a common and serious complication of human menopausal gonadotrophin/human chorionic gonadotrophin treatment. We evaluated the changes in the pituitary and ovarian hormone profiles and ultrasonographic follicular regression in 12 patients in whom human menopausal gonadotrophin was discontinued due to 'imminent' ovarian hyperstimulation. Following discontinuation, three distinct periods were observed: (i) days 1-2, the levels of oestradiol, testosterone and prolactin, and the total number of follicles continued to rise; (ii) days 3-6, the levels of oestradiol, testosterone and prolactin declined sharply and the total number of follicles was reduced significantly, while the large and medium sized follicles continued to increase. Levels of follicle-stimulating hormone and luteinizing hormone gradually declined to reach their lowest levels by days 5-6 and then increased. (iii) Thereafter the number of follicles and steroid output declined to early follicular phase levels. We conclude that discontinuation of human menopausal gonadotrophin and withholding human chorionic gonadotrophin in cycles with laboratory signs of 'imminent' ovarian hyperstimulation syndrome, allows regression of the ovarian ultrasonographic finding and prevents the development of clinical symptoms. However, if rescue of the cycle is attempted, human chorionic gonadotrophin should be given during the first 4 days after discontinuation of stimulation.

Topics: Adult; Estradiol; Female; Follicle Stimulating Hormone; Humans; Luteinizing Hormone; Menotropins; Ovarian Follicle; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Prolactin; Testosterone; Time Factors; Ultrasonography

During the last decade, 154 patients treated with human menopausal gonadotropin human chorionic gonadotropin developed hyperstimulation necessitating hospitalization in 201 cycles. Moderate ovarian hyperstimulation occurred in 116 of the patients and severe ovarian hyperstimulation in 34. Sixteen patients underwent operative procedures. Twelve patients underwent puncture of the pleura or abdomen to drain symptomatic hydrothorax or ascites, with clinical improvement of the symptoms in all of them. Three patients had coagulation abnormalities, and 1 patient had thromboembolic phenomena. Hyperstimulation seems to be associated with an increased pregnancy rate, since seventy-five pregnancies (35%) occurred in the study group. Appropriate monitoring can reduce the rate of OHSS but it should be kept in mind that death due to OHSS may occur.

Topics: Adult; Chorionic Gonadotropin; Female; Humans; Infertility, Female; Menotropins; Ovarian Hyperstimulation Syndrome; Ovulation Induction