Annemarie G.M.G.J. Mulders

Follicle-stimulating hormone receptor polymorphisms in women with normogonadotropic anovulatory infertility

OBJECTIVE To assess the incidence of different FSH receptor genotypes in normogonadotropic anovulatory infertile women (World Health Organization class II) and normo-ovulatory controls and to correlate these genotypes with baseline characteristics and ovarian responsiveness during ovulation induction. DESIGN Cross-sectional study. SETTING University hospital. PATIENT(S) Thirty normo-ovulatory controls and 148 normogonadotropic anovulatory infertile women. INTERVENTION(S) All participants underwent a standardized evaluation that included cycle history, body mass index measurement, and transvaginal ultrasonography of ovaries. Fasting blood samples were obtained for endocrine evaluation. Ovarian responsiveness to FSH in normogonadotropic anovulatory infertile women was assessed during ovulation induction, and DNA was analyzed to determine the FSH receptor genotype. MAIN OUTCOME MEASURE(S) Prevalence of FSH receptor polymorphisms, baseline serum FSH levels, amount of FSH administered, duration of stimulation, and ovarian response dose. RESULT(S) The Thr/Thr 307 genotype was significantly less prevalent (52% vs. 23%) and the Ser/Ser 680 polymorphism was significantly more prevalent (40% vs. 16%) in patients compared with controls. Normogonadotropic anovulatory infertile women with the Ser/Ser 680 polymorphism presented with higher median FSH serum levels (5.2 IU/L [range, 2.4-9.7 IU/L]) than did those with the Asn/Asn 680 (4.6 IU/L [range, 1.4-5.8 IU/L) and Asn/Ser 680 (4.5 IU/L [range, 1.8-9.7 IU/L) variants. However, ovarian responsiveness to FSH was similar among anovulatory women with the various polymorphisms. CONCLUSION(S) Normogonadotropic anovulatory infertile patients have a different FSH receptor genotype than do normo-ovulatory controls. Although this characteristic is associated with increased baseline FSH serum levels, altered ovarian sensitivity to exogenous FSH during ovulation induction could not be established.

Prediction of chances for success or complications in gonadotrophin ovulation induction in normogonadotrophic anovulatory infertility

This follow-up study evaluated whether initial screening characteristics predict treatment outcome of gonadotrophin induction of ovulation. One hundred and fifty-four women with normogonadotrophic anovulatory infertility for whom clomiphene citrate induction of ovulation was unsuccessful were included in the present study. Daily FSH injections were initiated on day 3-5 after spontaneous or progestagen-induced withdrawal bleeding. In most patients, a dose finding low-dose step-up regimen was applied during the first treatment cycle in order to identify the individual FSH response dose. In all subsequent cycles, a step-down protocol was applied. Initial serum concentrations of LH, testosterone and androstenedione were significant predictors for the probability of multi-follicular development. FSH treatment resulted in a total of 67 (44%) ongoing pregnancies. Comparing those women who did, versus those who did not, achieve an ongoing pregnancy in a multivariate Cox regression analysis, initial serum insulin-like growth factor-I (IGF-I), testosterone and womens age entered into the final model (AUC = 0.67). The individual treatment outcome following gonadotrophin induction of ovulation may be predicted by initial screening characteristics.

IVF outcome in anovulatory infertility (WHO group 2) – including polycystic ovary syndrome – following previous unsuccessful ovulation induction

This follow-up study represents IVF treatment characteristics and outcomes in women with World Health Organization (WHO) group 2 anovulatory infertility after previous unsuccessful ovulation induction compared with controls. Furthermore, the possibility of initial screening parameters of these anovulatory women to predict IVF outcome was examined. Twenty-six patients with WHO 2 anovulatory infertility who failed to achieve a live birth following previous induction of ovulation (using clomiphene citrate as first line and exogenous FSH as second line) were compared with 26 IVF patients with tubal infertility matched for age, treatment period and treatment regimen. The WHO 2 patients underwent 49 IVF cycles, whereas the normo-ovulatory controls underwent 46 cycles. In WHO 2 patients 15 cycles were cancelled compared with six cycles in controls (P = 0.04). Cycles were predominantly cancelled due to insufficient response (P = 0.04). In cases in whom the cycle was cancelled, body mass index (BMI) was significantly higher (P < 0.001) in WHO 2 women compared with controls. Overall live birth rates were comparable (P = 0.9). Obese women suffering from WHO 2 anovulatory infertility are at an increased risk of having their IVF cycle cancelled due to insufficient response. Once oocyte retrieval is achieved, live birth rates are comparable with controls.

Influence of oral contraceptives on anthropomorphometric, endocrine, and metabolic profiles of anovulatory polycystic ovary syndrome patients.

OBJECTIVE To evaluate the influence of oral contraceptive pills (OCPs) on anthromorphometric, endocrine, and metabolic parameters in women with polycystic ovary syndrome (PCOS). DESIGN Retrospective cross-sectional cohort study for the period 1993-2011. SETTING Tertiary university hospital. PATIENT(S) PCOS patients, who never, ever, or at time of screening were using OCPs were included. A total of 1,297 patients, of whom 827 were white, were included. All PCOS patients diagnosed according to the Rotterdam 2003 consensus criteria were divided into three groups: current users, (n = 76; 6% of total), ever users (n = 1,018; 78%), and never users (n = 203; 16%). Ever users were subdivided based on the OCP-free interval. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Anthromorphometric (blood pressure, cycle duration) and ultrasound (follicle count, mean ovarian volume) parameters, endocrine (SHBG, testosterone, free androgen index, antimüllerian hormone [AMH]) and lipid profiles. RESULT(S) Current users and ever users were compared with never users. In current users, SHBG was increased and androgen levels decreased. Patients with an OCP-free interval of <1 year had a higher mean follicle count, higher AMH level, and increased serum androgen level compared with never users. SHBG levels remained increased until 5-10 years after cessation of OCP use. CONCLUSION(S) OCP use causes a milder phenotypic presentation of PCOS regarding hyperandrogenism. However, it does not alter parameters associated with increased health risks.

Placental development and function in women with a history of placenta‐related complications: a systematic review

Women with a history of placenta‐related pregnancy complications, such as preeclampsia, intrauterine growth restriction or preterm delivery, have an increased risk for recurrence of such complications. This recurrence is likely the result of underlying endothelial dysfunction that leads to abnormal placentation, especially in complications with an early onset. This study provides an overview of biomarkers of placental development and function in pregnancies from women with a history of placenta‐related complications.