menotropins and Obesity

Subfertility is defined as the condition of being less than normally fertile though still capable of effecting fertilization. When these subfertile couples seek assistance for conception, a thorough evaluation of male endocrine function is often overlooked. Spermatogenesis is a complex process where even subtle alterations in this process can lead to subfertility or infertility. Male endocrine abnormalities may suggest a specific diagnosis contributing to subfertility; however, in many patients, the underlying etiology is still unknown. Optimizing underlying endocrine abnormalities may improve spermatogenesis and fertility. This manuscript reviews reproductive endocrine abnormalities and hormone-based treatments.

Topics: Adrenal Hyperplasia, Congenital; Androgen-Insensitivity Syndrome; Aromatase Inhibitors; Chorionic Gonadotropin; Clomiphene; Follicle Stimulating Hormone, Human; Humans; Hyperprolactinemia; Hypogonadism; Infertility, Male; Male; Menotropins; Obesity; Reproductive Control Agents; Selective Estrogen Receptor Modulators; Tamoxifen; Thyroid Diseases

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

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

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

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

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

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

There are many methods that can be used to induce ovulation when there is a fault in ovulation in patients who have normal prolactin levels. These are: Bringing the weight to a normal level. Giving Clomiphene. Giving Tamoxifen. Giving cyclofenil and bromocriptine, which really have no more effect than giving a placebo. Giving gonadotrophins in a classical way. This is very useful where there is hypogonadic amenorrhoea but much less useful when the failure of ovulation occurs with normal gonadic function. It is accompanied by a risk of multiple pregnancies and of hyperstimulation, which should be monitored by ultrasound very strictly so that it cannot become too serious. The use of purified FSH which theoretically should be more adequate, at least in cases where the gonadic function is normal in spite of failure of ovulation. Pulsatile administration of LHRH, which in cases of hypothalamic amenorrhoea carries less total risk than giving gonadotrophins. Finally, wedge resection of the ovaries which is reversed for polycystic ovaries that are larger than normal in size, and allied methods. The first choice for hypogonadic hypothalamic amenorrhoea would seem to be the LHRH pump; and for failure of ovulation with normal gonadic function Clomiphene or Tamoxifen. When anti-oestrogens fail to correct these latter cases one can choose according to the case between gonadotrophins, choosing if possible pure FSH, and/or wedge resection. In the last resort in these cases the LHRH pump can be used. The frequent failure of these methods show that perhaps it is possible to create a hypogonadotrophic hypogonadism by giving agonists for a long time or antagonists to LHRH in such a way that a second attempt can be made to induce ovulation using gonadotrophins in better conditions of efficacy and safety.

Topics: Amenorrhea; Anovulation; Clomiphene; Cyclofenil; Epimestrol; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Hypogonadism; Hypopituitarism; Hypothalamic Diseases; Menotropins; Obesity; Ovary; Ovulation Induction; Tamoxifen; Thinness

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

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

The objective of this study was to assess the relationship between BMI and oocyte number and maturity in participants who underwent minimal stimulation (mini-) or conventional IVF.. Participants who underwent their first autologous cycle of either conventional (n = 219) or mini-IVF (n = 220) were divided according to their BMI to analyze IVF outcome parameters. The main outcome measure was the number of oocytes in metaphase II (MII). Secondary outcomes included the number of total oocytes retrieved, fertilized (2PN) oocytes, cleavage and blastocyst stage embryos, clinical pregnancy (CP), and live birth (LB) rates.. In conventional IVF, but not in mini-IVF, the number of total oocytes retrieved (14.5  ±  0.8 versus 8.8  ±  1.3) and MII oocytes (11.2 ± 0.7 versus 7.1 ± 1.1) were significantly lower in obese compared with normal BMI women. Multivariable linear regression adjusting for age, day 3 FSH, days of stimulation, and total gonadotropin dose demonstrated that BMI was an independent predictor of the number of MII oocytes in conventional IVF (p = 0.0004). Additionally, only in conventional IVF, BMI was negatively correlated with the total number of 2PN oocytes, as well as the number of cleavage stage embryos.. Female adiposity might impair oocyte number and maturity in conventional IVF but not in mini-IVF. These data suggest that mild ovarian stimulation might yield healthier oocytes in obese women.

Topics: Adult; Chorionic Gonadotropin; Clomiphene; Female; Fertility Agents, Female; Fertilization in Vitro; Humans; Infertility; Leuprolide; Linear Models; Menotropins; Metaphase; Obesity; Oocytes; Ovulation Induction; Pregnancy; Pregnancy Rate

We examined the impact of high leptin levels on the secretion of estradiol, inhibin A and inhibin B in obese and lean women during ovarian stimulation. Patients undergoing long-term pituitary suppression, ovarian stimulation and in vitro fertilization for non-endocrine reasons were included in this case-control study. Obese women (body mass index (BMI) > 28 kg/m(2); n = 17) were individually matched with lean women (BMI 20-25 kg/m(2); n = 17) for age and baseline follicle stimulating hormone and luteinizing hormone concentrations. Blood samples were collected in a previous menstrual cycle and 1-3 days apart throughout ovarian stimulation. Serum levels of estradiol, leptin, inhibin A and inhibin B were measured. Obese and lean women had similar serum concentrations of estradiol, inhibin A and inhibin B in the follicular and luteal phases of the spontaneous menstrual cycle, and throughout ovarian stimulation. Serum levels of leptin were higher in obese than in lean women, and increased during stimulation in both groups. In the obese group, area-under-the-curve (AUC) leptin levels correlated with AUC inhibin A levels. In the lean group, there was no correlation between AUC leptin levels and AUC levels of ovarian hormones. The results suggest that high leptin concentrations in vivo are not associated with impaired secretion of estradiol and dimeric inhibins during ovarian stimulation.

Topics: Body Mass Index; Case-Control Studies; Chorionic Gonadotropin; Estradiol; Female; Fertilization in Vitro; Gonadotropins; Humans; Inhibins; Leptin; Menotropins; Menstrual Cycle; Obesity; Ovulation Induction

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

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

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

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

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

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