Abnormalities in the serum insulin-like growth factor-1 axis in women with hyperandrogenism

Objective: To study the insulin-like growth factor-1 (IGF-1) axis in hirsute women.

Design: Controlled clinical study.

Setting: Tertiary care institutional hospital.

Patient(s): Forty hirsute women and 17 women with normal menstrual cycles.

Intervention(s): Basal and ACTH-stimulated samples were obtained, and sampling was repeated 1 (gonadal stimulation) and 21 (gonadal suppression) days after a single 3.75-mg IM dose of triptorelin. Controls did not receive triptorelin for ethical reasons.

Main Outcome Measure(s): Serum GH, IGF-1, IGF-binding protein-3 (IGFBP-3), insulin, glucose, total testosterone, sex hormone-binding globulin, E₂, and gonadotropin levels. Basal and ACTH-stimulated steroid precursors were measured.

Result(s): Patients with idiopathic hirsutism were identified by normal serum androgen levels (n = 17). Those with functional ovarian hyperandrogenism (n = 15) were identified by an increase in the serum testosterone level that normalized during gonadal suppression, whereas those with functional adrenal hyperandrogenism (n = 8) were identified by an initial increase in the testosterone level that persisted during gonadal suppression. The adrenal hyperandrogenism group had increased IGF-1 levels compared with the control, idiopathic hirsutism, and ovarian hyperandrogenism groups. Patients with ovarian hyperandrogenism had normal IGF-1 concentrations, but their IGFBP-3 concentrations were lower than those of controls. No differences were observed in GH levels between any of the groups. These results persisted when the influence of age was corrected for.

Conclusion(s): The IGF-1 axis appears to be involved in the pathogenesis of hyperandrogenism, especially in patients with adrenal hyperandrogenism, who have a clear increase in IGF-1 levels. Moreover, patients with ovarian hirsutism have decreased IGFBP-3 concentrations, which might enhance IGF-1 bioavailability.     

The presence of the 21-hydroxylase deficiency carrier status in hirsute women: phenotype-genotype correlations.

OBJECTIVE: To determine the role of heterozygosity for mutations in the 21-hydroxylase gene (CYP21) in the pathogenesis of hyperandrogenism. DESIGN: Controlled clinical study. SETTING: Tertiary care institutional hospital. PATIENT(S): Forty hirsute women and 13 healthy control women. INTERVENTION(S): The source of androgen excess was determined by the changes in serum testosterone levels in response to a single 3.75-mg i.m. dose of triptorelin. MAIN OUTCOME MEASURE(S): CYP21 molecular genetic analysis and serum 17-hydroxyprogesterone levels. RESULT(S): Eight patients and one control were heterozygous carriers of CYP21 mutations. Two patients with adrenal hyperandrogenism and one patient with ovarian hyperandrogenism, who carried the V281L mutation had an increased ACTH-stimulated 17-hydroxyprogesterone level (>4.1 ng/mL) that persisted during gonadal suppression. Another patient with adrenal hyperandrogenism carried the V281L mutation, and her ACTH-stimulated 17-hydroxyprogesterone level was elevated only during gonadal suppression. Four patients (three with idiopathic hirsutism, one with ovarian hyperandrogenism) and one control were carriers of CYP21 mutations typically associated with classic congenital adrenal hyperplasia but had normal basal and ACTH-stimulated 17-hydroxyprogesterone levels. Nine patients without CYP21 mutations had increased ACTH-stimulated 17-hydroxyprogesterone levels; these decreased to normal in six of the patients during gonadal suppression. CONCLUSION(S): The response of serum 17-hydroxyprogesterone to ACTH does not predict CYP21 carrier status. No clear concordance was found between the CYP21 genotype and the functional origin of androgen excess.     

Low leptin level in an obese hyperandrogenic woman--potential marker for androgen-secreting tumor.

Hyperandrogenism in postmenopausal women is due to ovarian hyperthecosis or an androgen-secreting ovarian/adrenal tumor. Making the correct diagnosis might be complicated due to the possible existence of an adrenal neoplasm secreting testosterone only, ectopic ovarian tissue or ectopic luteinizing hormone/human chorionic gonadotropin receptors in the adrenals, as well as the relatively low sensitivity of imaging techniques (computed tomography, magnetic resonance imaging) and vein catheterization for this type of pathology. We present the case of an obese postmenopausal woman with metabolic syndrome, hyperandrogenism (high testosterone levels, suppressed gonadotropins), adrenal macronodular hyperplasia and Leydig-cell ovarian tumor. At presentation she had low leptin levels despite high body fat content. After a catheter study left adrenalectomy was carried out but hyperandrogenism persisted. Then, bilateral oophorectomy with hysterectomy was performed and a small Leydig-cell tumor was found in the left ovary. Postoperatively, testosterone and gonadotropin levels were normal (postmenopausal) and leptin level became elevated without change in body mass index or body fat content. In conclusion, we speculate that low leptin levels in obese hyperandrogenic women might be a marker for androgen-secreting tumors.     

Low leptin level in an obese hyperandrogenic woman – potential marker for androgen-secreting tumor

Hyperandrogenism in postmenopausal women is due to ovarian hyperthecosis or an androgen-secreting ovarian/adrenal tumor. Making the correct diagnosis might be complicated due to the possible existence of an adrenal neoplasm secreting testosterone only, ectopic ovarian tissue or ectopic luteinizing hormone/human chorionic gonadotropin receptors in the adrenals, as well as the relatively low sensitivity of imaging techniques (computed tomography, magnetic resonance imaging) and vein catheterization for this type of pathology. We present the case of an obese postmenopausal woman with metabolic syndrome, hyperandrogenism (high testosterone levels, suppressed gonadotropins), adrenal macronodular hyperplasia and Leydig-cell ovarian tumor. At presentation she had low leptin levels despite high body fat content. After a catheter study left adrenalectomy was carried out but hyperandrogenism persisted. Then, bilateral oophorectomy with hysterectomy was performed and a small Leydig-cell tumor was found in the left ovary. Postoperatively, testosterone and gonadotropin levels were normal (postmenopausal) and leptin level became elevated without change in body mass index or body fat content. In conclusion, we speculate that low leptin levels in obese hyperandrogenic women might be a marker for androgen-secreting tumors.     

Comparison of leuprolide acetate and triptorelin in assisted reproductive technology cycles: a prospective,randomized study

OBJECTIVE: To compare the use of two depot GnRH-a, leuprolide and triptorelin, in long-suppression GnRH-a protocols. DESIGN: Prospective, randomized study. SETTING: An IVF unit of an academic medical center.Fifty-two women who underwent controlled ovarian hyperstimulation and IVF. INTERVENTION(S): Patients were prospectively randomized to receive 3.75 mg depot formulations of either leuprolide or triptorelin on days 21-23 of the menstrual cycle. Stimulation with gonadotropins was initiated after pituitary desensitization was achieved. MAIN OUTCOME MEASURE(S): The stimulation pattern and cycle outcomes were compared between the two groups. RESULT(S): Twenty-six patients were included in each group. No significant differences were observed in the patient age, estrogen, and P levels on day of hCG administration, gonadotropin dosage, number of oocytes retrieved, fertilization rate, percentage of high-quality embryos, and number of embryos transferred. However, significantly higher clinical implantation and pregnancy rates were found in the leuprolide group compared with the triptorelin group. CONCLUSION(S): A depot preparation of leuprolide is associated with higher implantation and pregnancy rates than a depot preparation of triptorelin when it is used in the midluteal phase as part of the long-suppression GnRH-a protocol in IVF.     

Virilization due to ovarian hyperthecosis in a postmenopausal woman

A 51-year-old woman presented with hirsutism and virilization of gradual onset. The serum gonadotropin concentrations were in the postmenopausal range, the serum testosterone concentration was markedly elevated (9.8 nmol/l) and the serum estradiol concentration (220 pmol/l) was elevated above the postmenopausal range. A selective venous catheterization study demonstrated raised serum testosterone and androstenedione levels in ovarian veins and suggested the presence of a left ovarian tumor. The raised peripheral estradiol level was shown to be due to ovarian hypersecretion. After bilateral oophorectomy the serum testosterone became normal. Ovarian histology revealed bilateral stromal hyperthecosis. Ovarian hyperthecosis is a rare but important cause of serum testosterone levels in the neoplastic range. This is the third case reported of postmenopausal virilization due to ovarian hyperthecosis and the first report of a selective venous catheterization study in such a patient.     

Gonadotropin suppression for the treatment of karyotypically normal spontaneous premature ovarian failure: a controlled trial.

OBJECTIVE: To determine if gonadotropin suppression improves ovarian follicle function or ovulation rates in patients with karyotypically normal spontaneous premature ovarian failure. DESIGN: Prospective, double-blind, placebo-controlled, crossover trial. SETTING: Tertiary care research institution. INTERVENTIONS: Two intervention phases lasting 4 months each: one placebo phase, and one treatment phase during which each patient received daily subcutaneous injections of 300 micrograms of the gonadotropin-releasing hormone agonist (GnRH-a) deslorelin. During both phases, patients took a standardized estrogen (E) replacement regimen. PATIENTS, PARTICIPANTS: Twenty-six patients with karyotypically normal spontaneous premature ovarian failure ranging in age from 18 to 39 years. MAIN OUTCOME MEASURES: We measured serum estradiol (E2) and progesterone (P) levels weekly during the 2 months after each intervention. We defined a serum E2 greater than 50 pg/mL (184 pmol/L) as evidence for ovarian follicle function and a serum P greater than 3.0 ng/mL (9.5 nmol/L) as evidence for ovulation. RESULTS: The GnRH-a therapy did not significantly enhance recovery of ovarian follicle function or the chance of ovulation. The power to detect a 40% and a 33% ovulation success rate with therapy was 0.95 and 0.83, respectively. We found evidence for ovarian follicle function in 11 of 23 women (48%), and 4 women (17%) ovulated. CONCLUSIONS: Patients with karyotypically normal spontaneous premature ovarian failure treated with E replacement did not benefit from the additional gonadotropin suppression achieved with GnRH-a. Because these patients have a significant possibility of spontaneous remission, attempts to induce ovulation should be limited to controlled trials designed to determine safety and effectiveness.     

Postmenopausal hyperandrogenism caused by a benign cystic teratoma: a case report

BACKGROUND: Mature, benign cystic teratomas of the ovary are common in reproductive-age women, but they are very rarely associated with androgen production and subsequent development of hirsutism or virilization. We describe a case of postmenopausal hirsutism and hyperandrogenism caused by a mature cystic teratoma as well as the 7 previously reported cases. CASE: A 55-year-old, postmenopausal woman presented with hirsutism and unilateral lower extremity edema. Pelvic ultrasound showed a complex cystic mass in the left ovary measuring 6.0 x 7.0 x 10 cm, and laboratory evaluations revealed progressively increasing testosterone levels. The patient underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy, with resection of a large, complex mass originating in the left ovary. The pathology department found 2 left, mature ovarian cystic teratomas containing a layer of Leydig cells. Postoperatively the patient experienced rapid normalization of the elevated testosterone level. CONCLUSION: Although rare, ovarian production of androgens resulting in hirsutism or virilization can occur with a hormonally active mature cystic teratoma.     

Pituitary desensitization for eight weeks after the administration of two distinct gonadotrophin-releasing hormone agonists

OBJECTIVE(S): The objective was to evaluate the duration of pituitary desensitization after the administration of 3.5 mg of triptorelin (T) and leuprolin (L) depot preparations in patients with endometriosis. STUDY DESIGN: Two groups of 30 patients received, on 21st day of the cycle, 3.75 mg i.m. of triptorelin (T group), and of leuprolin acetate (L group). From the first to the eighth week following gonadotrophin-releasing hormone agonists (GnRH-a) administration both groups underwent pelvic ultrasound and serum follicle-stimulating hormone (FSH), luteinizing hormone (LH) and estradiol (E2) evaluation. Statistical analysis was performed using the ANOVA test and the median test. A p-value < 0.05 was considered significant. RESULTS: Pituitary suppression was achieved from two to six and from two to seven weeks after the administration of 3.75 mg of leuprolin and triptorelin, respectively. FSH and LH serum levels were significantly higher in the L group than in the T group after the fourth week. CONCLUSIONS: Leuprolin and triptorelin depots (3.75 mg) promote satisfactory ovarian suppression lasting for six and seven weeks, respectively, after administration, with significantly different ambient levels of endogenous LH.     

Hyperandrogenism in a postmenopausal woman presenting with a metastatic ileum endocrine tumor

OBJECTIVE: To elucidate the mechanism of the hyperandrogenism found in a postmenopausal woman presenting an ileum endocrine tumor with ovarian metastases. DESIGN: Case report. SETTING: University hospital. PATIENT(S): A postmenopausal woman was referred for hirsutism. Basal plasma testosterone was high, 6.6 nM/L (normal, 相似文献   

Pregnancy after treatment with the insulin-sensitizing agent troglitazone in an obese woman with the hyperandrogenic, insulin-resistant acanthosis nigricans syndrome

OBJECTIVE: To report a case of unassisted pregnancy after 5 months of troglitazone treatment in a severely hyperandrogenic, insulin-resistant woman with acanthosis nigricans (HAIR-AN) previously managed with depot leuprolide acetate (LA) plus oral contraceptive and dexamethasone therapy. DESIGN: Case report. SETTING: Private infertility clinic. PATIENT(S): A 28-year-old African-American woman with excessive obesity (body mass index = 42 kg/m2) and HAIR-AN syndrome. INTERVENTION(S): Androgen suppression with depot LA plus oral contraceptive and dexamethasone therapy, troglitazone treatment resulting in normalization of fasting insulin and testosterone, spontaneous menses, and an unassisted pregnancy. MAIN OUTCOME MEASURE(S): Luteinizing hormone and testosterone concentrations, fasting insulin and glucose levels, insulin-glucose ratios, hCG levels, and ultrasound examinations. RESULT(S): Spontaneous menses followed by an intrauterine pregnancy after 5 months of treatment with troglitazone, an insulin-sensitizing agent, in a woman with severe HAIR-AN syndrome whose hyperandrogenism previously could be normalized only with depot LA plus oral contraceptive therapy and dexamethasone. CONCLUSION(S): Troglitazone treatment resulted in attenuation of both hyperinsulinemia and hyperandrogenism in an obese woman with HAIR-AN and resulted in resumption of menses and a spontaneous pregnancy.     

Managing a patient with presumed testosterone-secreting ovarian tumor.

We report the case of a 70-year-old woman who was presumed to have right ovarian testosterone-secreting tumor and was treated with long-acting gonadotropin-releasing hormone agonist therapy plus add-back hormone replacement therapy. The patient presented with various medical problems including hypertension, intracranial hemorrhage, myocardial infarction, unstable angina pectoris, and poor control of diabetic mellitus and had exhibited rapid symptoms of androgen excess such as progressive hirsutism and bilateral temporal balding for half a year. Tumor survey was negative except for an elevated testosterone level. Renal vein catheterization successfully detected a right ovarian androgen-secreting tumor. Because the patient was deemed medically unable to tolerate surgery, she received an alternative treatment consisting of 6 months of gonadotropin-releasing hormone-agonist (GnRH-a) and add-back hormone replacement therapy (HRT). Serum testosterone levels returned to normal limits after administration of the first dose of GnRH-a. A follow-up tumor survey was negative. The patient has been alive and free of disease for 8 months after six doses of GnRH-a. We conclude that this strategy might be used as urgent therapy in a medically compromised patient with presumed ovarian androgen-secreting tumor.     

Postmenopausal androgen secreting ovarian tumour: pathophysiological implications; a case report

Hyperandrogenism in women is usually accompanied by a disruption of the hypothalamic-pituitary-ovarian axis; however, the precise effect of chronically elevated androgens on this axis is poorly understood. We report a postmenopausal woman with a virilizing ovarian tumour in whom the effects of chronic testosterone secretion on the hypothalamic-pituitary axis was investigated. A 56-year-old woman was evaluated for hirsutism and hyperandrogenism of recent onset. Peripheral serum testosterone was high (19.4 nmol/l), while gonadotropins were below normal for a postmenopausal woman, FSH (19.7 IU/l) being higher than LH (10.3 IU/l). Four LH and 1 FSH pulse were detected over 4 h. A left intraovarian testosterone secreting tumour, shown by catheterization of the ovarian veins and containing imperfect crystalloids of Reinke, was excised. Postoperatively, peripheral testosterone became undetectable, while gonadotropins rose to normal postmenopausal values. This patient's LH/FSH ratio was less than 1, in contrast with other situations of chronic hyperandrogenism. This could be explained by the concomitant hypoestrogenic state, and/or the theoretical absence of inhibin. The interest of this case resides in that it constitutes an appropriate model for studying the effects of testosterone on LH and FSH secretion in the absence of the other two classically involved modulators, namely oestrogens and inhibin.     

Exogenous gonadotropin stimulation is associated with increases in serum androgen levels in in-vitro fertilization-embryo transfer cycles

Objective: To examine serum androgen profiles in women undergoing ovarian stimulation with exogenous gonadotropins in the setting of IVF-ET.

Design: Prospective study.

Setting: University hospital IVF-ET program.

Patient(s): Seventeen ovulatory women undergoing IVF-ET for endometriosis, male factor infertility, or tubal disease.

Intervention(s): A standard long protocol of GnRH agonist (GnRH-a) pretreatment (1 mg of leuprolide acetate SC for 10 days) was administered before ovulation induction with a urinary gonadotropin preparation.

Main Outcome Measure(s): After 10 days of GnRH-a treatment and on the day of hCG administration, serum concentrations of LH, T, androstenedione (A), sex hormone-binding globulin (SHBG), and DHEAS; the free androgen index (T/SHBG); and the number of follicles, oocytes, and embryos were assessed.

Result(s): Serum samples after 10 days of GnRH-a treatment showed incomplete LH suppression. While continuing the agonist during ovarian stimulation, LH values were suppressed further. However, serum T and A concentrations and the free androgen index showed a significant increase (samples drawn just before hCG administration). Serum T levels after 10 days of GnRH-a (before the administration of exogenous gonadotropins) were correlated negatively with the subsequent number of embryos.

Conclusion(s): Serum LH suppression with a conventional regimen of GnRH-a is incomplete in this heterogeneous group of ovulatory women. Exogenous gonadotropin stimulation results in a marked increase in ovarian androgen secretion.     

GnRH analogs: depot versus short formulations

Gonadotropin releasing hormone agonists (GnRH-a) are widely used in controlled ovarian hyperstimulation (COH) for assisted reproduction (ART). Two different formulations are now available: short formulations and depot formulation. Some authors have suggested that depot GnRH-a induce a too high pituitary suppression and have put forward protocols using reduced GnRH-a doses. A reduced dose of daily triptorelin is enough for pituitary suppression during ovarian stimulation but provides no significant improvement in IVF cycle outcome when compared with depot formulation in normally responding women. However, it seems to improve ovarian response and overall results in poor responding patients. Low doses of short GnRH-a allow shorter treatment, requiring lower amounts of gonadotropins. This possibility should be considered in view of its economic advantage.     

Effects of gonadotropin-releasing hormone (GnRH) agonist on pituitary and ovarian responses to pulsatile GnRH therapy in polycystic ovarian disease

Nine clomiphene citrate-resistant polycystic ovarian disease (PCOD) patients received intravenous gonadotropin-releasing hormone (GnRH) pulses before and immediately after 1 month of GnRH agonist (GnRH-a) therapy. Circulating gonadotropin and ovarian steroid levels, as well as follicular development, were measured throughout therapy. Results were compared with those obtained from five hypogonadotropic patients treated with GnRH pulses only who ovulated during six of seven treatment cycles. Only two PCOD patients ovulated normally with GnRH pulses before GnRH-a therapy. Aberrant gonadotropin and ovarian steroid secretory patterns were noted in the others. After GnRH-a, gonadotropin and ovarian steroid hormone levels were similar to those of the hypogonadotropic patients. Subsequent secretory responses to GnRH pulses were partially normalized. However, only two additional PCOD patients ovulated.     

Thecal cell reaction associated with an ovarian leiomyoma and presenting with virilization

A 56-year-old woman presented with marked hirsutism and virilization of gradual onset. Menstruation had ceased at 43 years. The serum testosterone was grossly elevated (49 nmol/l) with levels of estradiol well above the postmenopausal range (200 pmol/l). Both serum testosterone and estradiol levels showed a marked but transient increase during the administration of the GnRH analog, buserelin. This indicated that the release of these steroids was under gonadotropin control. Bilateral oophorectomy revealed a greatly enlarged left ovary, and histology demonstrated a leiomyoma of the ovary with marked thecal reaction, which was probably responsible for the elevated serum testosterone and virilization. Testosterone levels returned to normal after bilateral oophorectomy. Excessive thecal androgen production associated with non-epithelial ovarian tumors is extremely uncommon and the response to buserelin has not previously been reported.     

Characterization of hyperandrogenism with insulin-resistant diabetes type A

The characterization of the hyperandrogenism of two sisters with type A insulin-resistant diabetes and hirsutism is presented. Testosterone (T) and androstenedione levels were elevated in peripheral serum. These were not markedly affected by infusion of adrenocorticotropic hormone. In patient 1 glucocorticoid suppression decreased T levels by 50% and androstenedione levels by 30% but had no effect on them in patient 2. Estrogen-progestin suppression markedly reduced testosterone levels in both patients. The blood production of T in patient 1 was 0.8 mg/day and in patient 2 was 4.5 mg/day, both of which are elevated. Selective venous catheterization in patient 2 revealed markedly elevated testosterone levels in the ovarian veins, and polycystic ovaries were found at subsequent laparotomy. These endocrine studies have shown that the source of excessive testosterone in these patients is excessive production by the ovaries, and it can be suppressed by oral contraceptives.     

Testosterone levels in female partners of infertile couples. Relationship between androgen levels in the woman, the male factor, and the incidence of pregnancy.

Plasma testosterone levels were measured in the female partners of 146 consecutive infertile couples. The incidence of hyperandrogenism in the woman was correlated with ovarian function, incidence of pregnancy, male factor, and response of plasma testosterone levels to prednisone treatment. Over 70 per cent of the patients had pretreatment testosterone levels above 40 ng. per 100 ml. while after a minimum of two months of therapy approximately 80 per cent had levels below 40 ng. per 100 ml. High levels of plasma testosterone were associated with significant prolongation of the follicular phase of the cycle and increased incidence of amenorrhea or anovulation. An over-all pregnancy rate of 50.4 per cent resulted from the treatment. A direct relationship between pregnancy rates and sperm density as well as between pregnancy rates and degree of suppression of plasma testosterone after therapy was observed. These results demonstrate a high incidence of hyperandrogenism in female partners of infertile couples. The effectiveness of glucocorticoid treatment appears to be related to suppression of excessive androgen levels. The data also suggest that infertility is a relative state related to the fertility potential of each member of the couple. Improvement of the fertility potential of either member may result in conception.     

A preliminary study on reduced dose (33 or 25 microg) gonadotropin-releasing hormone agonist long protocol for multifollicular ovarian stimulation in patients with high basal serum follicle-stimulating hormone levels undergoing in vitro fertilization-embryo transfer.

The aim of the present study was to evaluate the clinical efficacy of half-dose (50 mug) and further reduced dose (33 or 25 mug) gonadotropin-releasing hormone agonist (GnRH-a; triptorelin) long protocols for multifollicular ovarian stimulation (MFOS) for patients with high basal serum follicle-stimulating hormone (FSH) level undergoing in vitro fertilization and embryo transfer (IVF-ET). One hundred and two IVF-ET cycles performed in 84 infertile patients with high basal serum FSH (>10.0 mIU/ml) were included in this retrospective study. Study subjects were assigned to two groups: continuous half-dose GnRH-a long protocol (group A, n = 63) vs. further reduced dose GnRH-a long protocol (group B, n = 39) from half-dose at the start of GnRH-a to one-third or one-quarter dose after pituitary downregulation. Exogenous FSH or human menopausal gonadotropin was administered for MFOS in step-down mode, four or fewer embryos were transferred, and the outcomes of MFOS were compared between the two groups. Serum estradiol (E(2)) level on the day of human chorionic gonadotropin administration was significantly higher in group B (mean +/- standard deviation (SD): 1318.3 +/- 1120.4 vs. 2054.9 +/- 1773.5 pg/ml, p = 0.015). The number of transferable and good-quality embryos was also significantly higher in group B (mean +/- SD: 2.9 +/- 1.7 vs. 3.7 +/- 2.0, p = 0.027; 1.8 +/- 1.4 vs. 2.7 +/- 2.0, p = 0.020). No statistically significant difference in the outcomes was observed with respect to the dose of gonadotropins administered, the number of oocytes retrieved or the clinical pregnancy rate. In conclusion, GnRH-a long protocol with a reduced dose, tapered from the starting half-dose to a third or a quarter of the normal dose after pituitary suppression, may be beneficial for MFOS in IVF-ET patients with a high basal serum FSH level. A further prospective randomized controlled study on a larger scale is needed to confirm these findings.