Low-dose Follicle-stimulating Hormone Research Articles

Discovery and Preclinical Development of Orally Active Small Molecules that Exhibit Highly Selective Follicle Stimulating Hormone Receptor Agonism.

An orally active follicle stimulating hormone receptor allosteric agonist would provide a preferred treatment for over 16 million infertile women of reproductive age in low complexity methods (ovulation induction-intrauterine insemination) or in high complexity methods (controlled ovarian stimulation-in vitro fertilization). We present two oral follicle stimulating hormone receptor allosteric agonist compounds that have the desired pharmacology, drug metabolism, pharmacokinetics, and safety profile for clinical use. These molecules provide a single agent suitable for ovulation induction-intrauterine insemination or controlled ovarian stimulation-in vitro fertilization that is more convenient for patients and achieves similar preclinical efficacy as rec-hFSH. TOP5668, TOP5300 were evaluated in vitro in Chinese hamster ovary cells transfected with individual glycoprotein receptors measuring cAMP (FSHR, LH/CGR, thyroid stimulating hormone receptor). TOP5668 was found to have solely follicle stimulating hormone receptor allosteric agonist activity while TOP5300 was found to have mixed follicle stimulating hormone receptor allosteric agonist and LHR-AA activity. Both compounds stimulated concentration-dependent increases in estradiol production from cultured rat granulosa cells in the presence or absence of low dose rec-hFSH, while only TOP5300 stimulated testosterone production from rat primary Leydig cells. In pooled human granulosa cells obtained from patients undergoing controlled ovarian stimulation-in vitro fertilization, TOP5300 stimulated 7-fold greater maximal estradiol response than rec-hFSH and TOP5668 was 10-fold more potent than TOP5300. Both TOP5300 and TOP5668 stimulated follicular development in immature rat to the same efficacy as recombinant follicle stimulating hormone. In mice treated with TOP5300, in the presence of low dose of follicle stimulating hormone, there were no differences in oocyte number, fertilization rate, and hatched blastocyst rate in mice with TOP5300 and low dose follicle stimulating hormone vs. reference proteins pregnant mare serum gonadotropin or high dose rec-hFSH. ADME/PK and safety profiles were favorable. In addition, there was no appreciable activity on thyroid hormones by TOP5300 in 14-days toxicological study in rat or dog. The selected lead compound, TOP5300 stimulated a more robust increase in estradiol production from granulosa-lutein cells from women with polycystic ovarian syndrome patient compared to rec-hFSH. Conclusions: Two novel oral FSHR allosteric agonist, TOP5668 and TOP5300, were found to mimic the biological activity of rec hFSH in preclinical studies. Both compounds led to folliculogenesis and superovulation in rat and mice. Specifically, TOP5300 led to a similar number of ovulated oocytes that fertilized and developed into hatched blastocysts in mice when compared to rec-hFSH. The safety profile demonstrated lack of toxicity.

Management Infertility by Hormones Replacement Therapy in Women with Polycystic Ovarian Syndrome

Polycystic ovary syndrome (PCOS) is an endocrine-metabolic disorder characterized by multiple hormonal imbalances; the clinical presentation dominated by manifestations of hyperandrogenism, which generates short- and long-term consequences on female health sterility, infertility is one of the most alarming associated morbidities. Forty women (28.9 ± 0.8 years old) with polycystic ovarian syndrome had infertility and there were enrolled in these clinical trials and randomly allocated into two groups. Group one and Group two were given treated infertility drugs (Clomid 5 mg for 5 days) and recombinant follicle-stimulating hormone (rFSH) 75 IU for long and short duration to get pregnant. Serum testosterone, progesterone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) of both groups were measured when women diagnosed as PCOS. The results showed that women which treated by low-dose recombinant FSH 75 IU for 3 days consequently (Group one) have significant decreased LH, while progesterone and FSH significantly increased after treated by hormone therapy P ≥ 0.05 while after treatment with recombinant FSH IU for 5 days (Group two), the result showed non-significant effect as compared with the first group. Concluded: Increase pregnant rate and decrease over stimulation syndrome among infertile women associated with polycystic overian syndrome, when treated with applicated low dose and short term by rFSH hormone.

Ovulation induction in polycystic ovary syndrome.

The objective of this narrative review was to suggest a rational order of treatment choices in anovulatory women with polycystic ovary syndrome (PCOS), for whom a multitude of treatment options exist. In obese/overweight women with PCOS the importance of weight reduction should be stressed. Inositol, a dietary supplement with a documented effect on ovulation and without adverse effects in the doses recommended, may be suggested. Additional first-line medical alternatives include insulin sensitizers, selective estrogen receptor modulators, and aromatase inhibitors. Of these, the aromatase inhibitor letrozole and the combination of clomiphene citrate and metformin have the highest rates of ovulation and live birth. Second-line treatments are ovarian electrocautery and low-dose follicle-stimulating hormone stimulation. Controlled ovarian stimulation with in vitro fertilization, should be considered the last option as it carries a significant risk of ovarian hyperstimulation syndrome in patients with PCOS.

Pilot study of the optimal protocol of low dose step-up follicle stimulating hormone therapy for infertile women.

PurposeTo evaluate the optimized protocol of low dose follicle‐stimulating hormone (FSH) therapy that has a starting dose of 50 IU/62.5 IU with a small increment dose (12.5 IU) for women with World Health Organization (WHO) II ovulatory disorder and unexplained infertility.MethodsAnovulatory women with WHO group II ovulatory disorder (ovulation induction [OI] patients, n = 29), and with an unexplained infertility (ovarian stimulation [OS] patients, n = 21) were enrolled. The protocol of low dose step‐up FSH therapy was optimized for the starting dose as 50 IU (body mass index [BMI] < 20 group) and 62.5 IU (BMI ≥ 20 group) with the increment dose of 12.5 IU. Study outcomes were ovulation, monofollicular development and other variables.ResultsIn the OIpatients, the ovulation rate was 100% (BMI < 20 group) and 90.9% (BMI ≥ 20 group). Monofollicular development was 80.0% (BMI < 20) and 77.3% (BMI ≥ 20). The pregnancy rate was 60% (3/5 BMI < 20) and 18.2% (4/22 BMI ≥ 20). There was no multiple pregnancy. In the OSpatients, the ovulation rate was 100%. Monofollicular development was 85.7% (BMI < 20) and 76.6% (BMI ≥ 20). No pregnancy was achieved in the OSpatients.ConclusionOptimized protocol of low dose FSH therapy setting a starting dose 50 IU/62.5 IU by BMI with an increment dose of 12.5 IU was safe and highly effective in WHO group II anovulatory patients. However, this protocol seemed uneffective for patients with unexplained infertility.

Gonadotropin ratio affects the in vitro growth of rhesus ovarian preantral follicles

In vitro follicle growth (IVFG) strategy is critical in the fertility preservation of cancer survivors; however, its optimal protocol needs to be developed using primate models since the availability of...

Effect of oral administration of low-dose follicle stimulating hormone on hyperandrogenized mice as a model of polycystic ovary syndrome.

BackgroundPolycystic Ovary Syndrome (PCOS) is a widespread reproductive disorder characterized by a disruption of follicular growth and anovulatory infertility. In women with PCOS, follicular growth and ovulation can be induced by subcutaneous injections of low doses of follicle stimulating hormone (FSH). The aim of this study was to determine the effect of oral administration of recombinant human FSH (rhFSH) on follicle development in a PCOS murine model. Moreover, since it is unlikely that intact rhFSH is present into the circulation after oral administration, the biological activity of a peptide fragment, derived from the predicted enzymatic cleavage sites with the FSH molecule, was investigated in vitro on cumulus-enclosed oocytes (COCs).MethodsFemale peripubertal mice were injected with dehydroepiandrosterone (DHEA) diluted in sesame oil for 20 consecutive days and orally treated with a saline solution of rhFSH. A control group received only sesame oil and saline solution. At the end of treatments, blood was analyzed for hormone concentrations and ovaries were processed for morphological analysis. The presumptive bioactive peptide was added during in vitro maturation of bovine COCs and the effects on cumulus expansion and on maturation rate were evaluated.ResultsDHEA treatment increased serum levels of testosterone, estradiol and progesterone as well as the percentage of cystic follicles. Orally administered rhFSH restored estradiol level and reduced the percentage of cystic follicles. Despite these results indicating a reduction of the severity of PCOS in the mouse model, the presumptive bioactive peptide did not mimic the effect of rhFSH and failed to induce bovine cumulus expansion and oocyte maturation in vitro.ConclusionsAlthough further studies are needed, the present data supports the concept that orally administrated FSH could attenuate some of the characteristic of PCOS in the mouse model.Electronic supplementary materialThe online version of this article (doi:10.1186/s13048-015-0192-9) contains supplementary material, which is available to authorized users.

Retransplantation of Cryopreserved Ovarian Tissue

Cryopreserved ovarian tissue can be retransplanted to restore fertility after radiation or chemotherapy. To date, 15 live births after retransplantation have been reported worldwide. We report the first pregnancy and the first live birth after retransplantation in Germany. A 25-year-old female patient received initial chemotherapy and radiation of the mediastinum for Hodgkin's lymphoma in 2003 and suffered a relapse two years later. Ovarian tissue was laparoscopically removed and cryopreserved, and she was then treated with high-dose chemotherapy and stem cell transplantation. She remained in remission for 5 years and she could not conceive during this time. The cryopreserved ovarian tissue was thawed and laparoscopically retransplanted into a peritoneal pouch in the ovarian fossa of the right pelvic wall. Three months later, her menopausal symptoms resolved, and she had her first spontaneous menstruation. Six months after retransplantation, after two normal menstrual cycles, low-dose follicle stimulating hormone (FSH) treatment induced the appearance of a dominant follicle in the tissue graft. Ovulation was then induced with human chorionic gonadotropin (HCG), whereupon the patient conceived naturally. After an uncomplicated pregnancy, she bore a healthy child by Caesarean section on 10 October 2011. Histological examination of biopsy specimens revealed that the ovarian tissue of the graft contained follicles in various stages of development, while the original ovaries contained only structures without any reproductive potential. This was the first live birth after retransplantation of cryopreserved ovarian tissue in Germany and also the first case with histological confirmation that the oocyte from which the patient conceived could only have come from the retransplanted tissue. In general, young women who will be undergoing chemotherapy and/or radiotherapy for cancer must be informed and counseled about the available options for fertility preservation.

Effects of low-dose follicle-stimulating hormone administration on follicular dynamics and preovulatory follicle characteristics in dairy cows during the summer

The well-documented phenomenon of reduced conception rate in dairy cows during the hot season involves impaired functioning of the ovarian follicles and their enclosed oocytes. Three experiments were performed to examine the administration of low doses of follicle-stimulating hormone (FSH) to induce turnover of follicles that are damaged upon summer thermal stress and to examine whether this FSH administration has beneficial effects on preovulatory follicles. In experiment 1, synchronized heifers were treated with 100 mg of Folltropin-V (n = 7) or 4.4 mg of Ovagen (n = 6) on day 3 of the estrous cycle. Treatment with both FSH sources resulted in greater ( P < 0.05) numbers of follicles than in control animals (n = 12) on day 6 of the estrous cycle, indicating that low doses of FSH can increase the number of emerging follicles in a follicular wave. In experiment 2, milking cows were assigned to a control group (n = 4) or treated with 2.2 mg (FSH-2.2; n = 6) or 4.4 mg (FSH-4.4; n = 5) Ovagen. Follicle-stimulating hormone was administrated on day 3 or 4 and day 10 or 11 of the estrous cycle, coinciding with emergence of the first and second follicular waves, respectively. The number of follicles emerging during the first wave tended to be higher ( P < 0.1) in FSH-4.4-treated cows than in controls. The second-wave dominant follicles emerged 2 d later in the treated cows and were smaller in diameter ( P < 0.05) than controls, 2 d before aspiration. Despite being younger, the preovulatory follicles of FSH-4.4 cows expressed a steroidogenic capacity that was similar to controls with a tendency toward greater insulin concentrations ( P < 0.09). In experiment 3, milking cows were assigned to a control group (n = 6) or treated with 4.4 mg Ovagen (FSH-4.4; n = 6). Follicle-stimulating hormone was administrated on day 3 and day 12 or 13 of the estrous cycle. The number of emerging follicles was higher ( P < 0.05) in the treated vs control cows. However, the features of the preovulatory follicle developed in the subsequent cycle did not differ between groups. In summary, low doses of FSH can efficiently induce follicular turnover accompanied by a modest effect on the preovulatory follicle of the treated cycle. It appears that the administration of low doses of FSH, precisely timed to synchronize with the emergence of follicular waves, might have a beneficial effect on the preovulatory follicle and its enclosed oocyte.

Fertility Preservation in Breast Cancer Patients: A Prospective Controlled Comparison of Ovarian Stimulation With Tamoxifen and Letrozole for Embryo Cryopreservation

To develop safe ovarian stimulation methods to perform in vitro fertilization (IVF) in breast cancer patients who wish to preserve their fertility via embryo cryopreservation before chemotherapy. Sixty women (age range, 24 to 43 years) with breast cancer were prospectively studied. Twenty-nine patients underwent 33 ovarian stimulation cycles with either tamoxifen 60 mg/d alone (Tam-IVF) or in combination with low-dose follicle-stimulating hormone (TamFSH-IVF) or letrozole 5 mg in combination with FSH (Letrozole-IVF). After IVF, all resultant embryos were cryopreserved to preserve fertility. Recurrence rates were compared with controls (n = 31) who elected not to undergo IVF. Compared with Tam-IVF, both TamFSH-IVF and Letrozole-IVF patients had greater numbers of follicles (2 +/- 0.3 v 6 +/- 1 and 7.8 +/- 0.9, respectively; P < .0001), mature oocytes (1.5 +/- 0.3 v 5.1 +/- 1.1 and 8.5 +/- 1.6, respectively; P < .001), and embryos (1.3 +/- 0.2 v 3.8 +/- 0.8 and 5.3 +/- 0.8, respectively; P < .001). Peak estradiol (E2) levels were lower with Letrozole-IVF and Tam-IVF compared with TamFSH-IVF. After 554 +/- 31 days (range, 153 to 1,441 days) of follow-up, cancer recurrence rate was similar between IVF and control patients (three of 29 v three of 31 patients, respectively; hazard ratio, 1.5; 95% CI, 0.29 to 7.4), and this estimate was not affected by cancer stage. The combination of low-dose FSH with tamoxifen (TamFSH-IVF) or letrozole (Letrozole-IVF) results in higher embryo yield compared with Tam-IVF. Recurrence rates do not seem to be increased, but the letrozole protocol may be preferred because it results in lower peak E2 levels.

Management of Infertility in Women with Polycystic Ovary Syndrome

The management of infertility in women with polycystic ovary syndrome (PCOS) centers around options for inducing ovulation. This is an evidence-based review of the management of PCOS, which includes a MEDLINE search of publications between 1986 and May 2005 and a search of the Cochrane Database. Weight loss, exercise, and metformin will induce ovulation in many insulin-resistant women and obese women with PCOS, and should always be the first-line treatment. Ovulation induction has been performed with clomiphene citrate (clomifene) as the first-line treatment, but the use of aromatase inhibitors has been shown to be as successful. The strategies for reducing the risks of gonadotropin therapy such as low-dose follicle-stimulating hormone (FSH) stimulation and the addition of metformin are discussed. Both gonadotropin releasing-hormone agonists and antagonists are equally effective in in vitro fertilization stimulation in conjunction with FSH therapy. Metformin may have a benefit in pregnancy in reducing the risks of miscarriage and diabetes mellitus; however, prospective trials are still lacking.

The impact of insulin resistance on the outcome of ovulation induction with low-dose follicle stimulating hormone in women with polycystic ovary syndrome.

In this study we examined the possible correlation between insulin metabolism and outcome of gonadotrophin stimulation in infertile clomiphene citrate resistant women with polycystic ovary syndrome (PCOS). The patient group comprised 42 women who were entered into the study in a consecutive fashion. Following performance of the CIGMA (continuous infusion of glucose with model assessment) test, 17 women were classified as insulin resistant and 25 women as non-insulin resistant. Each woman received up to two cycles of low-dose follicle stimulating hormone (FSH) stimulation starting with 75 IU of FSH for 1 week, giving a total of 70 cycles performed. The insulin resistant PCOS women required more gonadotrophin and a longer time to achieve follicular maturation. By multiple regression gonadotrophin consumption correlated best with CIGMA value but not with fasting insulin concentration or body mass index. In the insulin resistant PCOS women 10 out of 29 cycles were cancelled due to a multifollicular response, while only one of 41 cycles was cancelled in the non-insulin resistant PCOS women. Although ovulation rate in completed cycles was similar between the groups, the conception rate was significantly better in the non-insulin resistant PCOS women. In conclusion, in PCOS women insulin resistance seems to be an unfavourable condition resulting in an elevated cancellation rate and a low conception rate following low-dose FSH stimulation.

Responses of polycystic ovarian syndrome and related variants to low-dose follicle stimulating hormone

Objective: To determine whether patients with classical polycystic ovarian syndrome (PCOS) respond differently to low-dose FSH therapy in comparison with anovulatory patients (PCOS-like) where only some features of PCOS are present. Methods: Two groups of patients were studied. The PCOS group (25 patients, 51 cycles) and the PCOS-like group (38 patients, 57 cycles) were treated with the same protocol of purified FSH, commencing with an initial dosage of 75 IU/day and increasing by 37.5 IU/day after 14 days, where necessary. Estradiol levels and ultrasonographic evidence of follicular development were used for monitoring. Results: PCOS patients required more ampules of FSH, needed more days of gonadotropin stimulation, secreted higher levels of E 2 and had increased numbers of intermediate follicles compared to the PCOS-like group. Conclusions: This study demonstrated significant differences between PCOS and other PCOS-like conditions when treated with low-dose FSH. Classification of the subvariants of PCOS may have therapeutic implications.

Chronic low-dose follicle-stimulating hormone compared with clomiphene/human menopausal gonadotropin for induction of ovulation

Concurrent administration of clomiphene can reduce the amount of gonadotropins required for induction of ovulation. Recently, follicle-stimulating hormone (FSH) administered in a chronic, low-dosefashion has been reported to give satisfactory pregnancy rates. We compared the conventional clomiphene/human menopausal gonadotropin (hMG) with the chronic, low-dose FSH regimen for induction of ovulation in 87 patients over 110 cycles. The clomiphene/hMG regimen required half the amount of gonadotropin-compared to the chronic FSH regimen to achieve follicular maturation. Despite the reduced amount of gonadotropin, the clomiphene/hMG regimen induced a mean fourfold higher level of estradiol production and was associated with significantly greater numbers of large and intermediate-sized follicles compared to the chronic FSH regimen. The proportion of clomiphene/hMG cases with multifollicular development and overstimulation was therefore high (30%). In contrast, the chronic FSH regimen, despite requiring larger amounts of gonadotropin and longer periods of treatment, resulted in unifollicular development, low rates of overstimulation and improved pregnancy rates. We conclude that although clomiphene.

Increase in androgen:estrogen ratio specifically during low-dose follicle-stimulating hormone therapy for polycystic ovary syndrome

Increase in androgen:estrogen ratio specifically during low-dose follicle-stimulating hormone therapy for polycystic ovary syndrome

Low-dose follicle-stimulating hormone treatment for polycystic ovarian disease

Objective: An attempt was made to induce ovulation with low-dose follicle-stimulating hormone (FSH) in clomifene-resistant women with anovulatory polycystic ovarian disease (PCOD). Methods: Twenty-two PCOD patients were treated with a low-dose protocol of purified urinary FSH, starting with 75 IU/day and increasing every 7 days by 37.5 IU/day, if necessary. Monitoring was based on ultrasound scanning and estradiol measurements. Results: Twenty-eight of the thirty-one cycles induced were ovulatory, the majority being uniovulatory (58%). No multiple pregnancies occurred. There was a small number of cancelled cycles (12.9%). The prevalence of complications was low, with one case of ovarian hyperstimulation syndrome. Ovulation was induced by a small amount of FSH (15.1 ± 4.9 ampules). Conclusion: The use of the low-dose protocol permitted induction of ovulation safely and successfully in a selected group of PCOD patients. This therapy was associated with a high incidence of single dominant follicles and a very low multiple pregnancy rate.

Increase in androgen:estrogen ratio specifically during low-dose follicle-stimulating hormone therapy for polycystic ovary syndrome

To compare changes in serum androgens in women with polycystic ovary syndrome (PCOS) during ovulation induction with low-dose versus conventional urofollitropin. Prospective case-control study. Tertiary-care reproductive medicine center. Thirty-three women with PCOS who failed to conceive with clomiphene citrate therapy. Urofollitropin (low-dose, 75 IU; conventional dose, 150 IU) was administered IM daily. Therapy was monitored by serum E2 and vaginal sonography. Hormone determinations were performed by immunoassay. Serum E2, androstenedione (A), T, and LH levels. On the day of hCG administration, patients treated with low-dose therapy exhibited significantly higher ratios of A to E2 (3.5 +/- 0.5 versus 2.2 +/- 0.3 [mean +/- SEM]) and T to E2 (1.5 +/- 0.3 versus 1.0 +/- 0.1) compared with conventional urofollitropin therapy. The number of follicles > or = 16 mm in diameter was significantly lower with low-dose therapy (2.7 +/- 0.6 versus 5.4 +/- 0.4). Although low-dose therapy was associated with a reduction in the number of recruited follicles, the increase in androgen to E2 associated with this therapy may adversely affect oocyte quality and may explain the relatively high miscarriage rate reported in PCOS patients with this therapy.

The effects of a gonadotrophin-releasing hormone agonist on treatment with low dose follicle stimulating hormone in polycystic ovary syndrome

The objective of this study was to investigate whether the incidence of monofollicular growth during stimulation with low dose follicle stimulating hormone (FSH) changes when adjuvant gonadotrophin-releasing hormone agonist (GnRHa) pre-treatment is administered in polycystic ovary syndrome (PCOS). One group of patients (group 1) suffering from clomiphene resistant PCOS was stimulated with low dose FSH. The results were compared with those from another group of similar patients (group 2) subsequently stimulated with low dose FSH combined with GnRHa. In group 1 15 patients had 39 stimulation cycles performed; in group 2 13 patients had 33 stimulation cycles performed. In group 1 44% of cycles were monofollicular, whilst the corresponding figure in group 2 was 14% (P = 0.04). Evidence was found for postponed atresia in group 2. In both groups 1 and 2 inter-individual and intra-individual variability of the FSH dose inducing follicular growth were observed. We concluded that during the use of GnRHa, stimulation with low dose FSH less frequently resulted in monofollicular growth, possibly due to postponed atresia. Furthermore, the use of GnRHa does not abolish the inter- and intra-individual variability of the FSH dose inducing ongoing follicular growth.

Ovulation induction with low-dose follicle-stimulating hormone in women with the polycystic ovary syndrome.

Fifty infertile women with the polycystic ovary syndrome (PCOS) were treated for 66 cycles with low-dose FSH stimulation starting with 75 IU FSH for two weeks before eventual stepwise increases in the gonadotropin dose occurred. An unifollicular response was observed in 35 (53%) cycles and in 20 (30%) cycles there were two-three mature follicles. A multifollicular response (> 3 mature follicles) resulted in 11 (17%) cycles. One of the 66 cycles was complicated with the ovarian hyperstimulation syndrome. Twelve (22%) pregnancies were obtained following 55 completed cycles. All ongoing pregnancies were singleton gestations. The obese PCOS women required a longer period of stimulation and a higher amount of gonadotropin to achieve follicular maturation. However, there was no difference in cycle cancellation or pregnancy rate between obese and non-obese PCOS women. Thus low-dose FSH administration seems a safe stimulation regimen with a satisfactory conception rate in PCOS women.

Polycystic ovary syndrome: low-dose follicle stimulating hormone administration is a safe stimulation regimen even in previous hyper-responsive patients.

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.

A comparative, randomized study of low-dose human menopausal gonadotropin and follicle-stimulating hormone in women with polycystic ovarian syndrome

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