Reproductive health, obesity, and cardiometabolic risk factors among Samoan women.

OBJECTIVES: Obesity leads to deleterious effects on not only cardiovascular health but also on the reproductive health of women. We estimate the prevalence of menstrual irregularity and of polycystic ovarian syndrome (PCOS) in Samoan women, among whom obesity prevalence is extremely high. We explore the association of these reproductive health conditions with adiposity, cardiometabolic risk factors, and androgen levels. METHODS: A cross-sectional sample of Samoan women 25-39 years of age (n = 470) from a larger population-based genome-wide association study of adiposity and cardiometabolic disease was assessed for the prevalence of oligomenorrhea/amenorrhea (OM/AM) using a self-reported questionnaire. Serum androgens and anti-Müllerian hormone levels were assayed to determine hyperandrogenemia and presence of polycystic ovaries (PCO), respectively, using criterion values. PCOS was classified using NIH guidelines of having at least two of the three conditions: menstrual irregularity, hyperandrogenism, and PCO. We contrasted socio-demographic, reproductive health, and cardiometabolic risk factors between those with and without OM/AM and similarly for PCOS. RESULTS: The prevalence of OM/AM was 7.4% (95% CI: 5.1, 9.8), and women with OM/AM had significantly higher central adiposity. PCOS was estimated at 6.8% (95% CI: 4.5, 9.1), and those with PCOS were younger but had higher overall and central adiposity measures, higher triglycerides, and higher prevalence of insulin resistance than women without PCOS. CONCLUSIONS: The prevalence of menstrual irregularity and PCOS are less than hypothesized given the high levels of adiposity in this population. Nevertheless, Samoan women with menstrual irregularity and other features of PCOS have significantly poorer metabolic health.

Circulating cell free DNA testing: are some test failures informative?

OBJECTIVE: The proportion of circulating cell free DNA derived from the feto-placental unit (fetal fraction or FF) correlates with test success and interpretation reliability. Some fetal disorders are associated with systematically lower FF, sometimes resulting in noninformative results. METHODS: We analyzed results from pregnancies tested in a nested case/control study derived from a cohort of 4664 high-risk pregnancies. Low FF was defined before and after adjusting for maternal weight and gestational age. RESULTS: Compared with euploid pregnancies, the median FF was significantly higher in Down syndrome pregnancies (ratio 1.17) and significantly lower in trisomy 18 and triploid pregnancies (ratios 0.71 and 0.19, respectively). Among 2157 pregnancies tested, 13 (0.6%) had FF <3.0% (all noninformative), including three trisomy 18 and three triploidy fetuses. After adjustment, 16 pregnancies (0.7%) had FF <0.3 multiples of the median (six informative), including one trisomy 18 and three triploidy fetuses. Modeled positive predictive values for low and high-risk populations were 7% and 30%, respectively. CONCLUSION: Among women with noninformative results attributable to low FF, trisomy 18 and/or triploidy risk are sufficiently high to warrant offering additional assessments (e.g. ultrasound). If the testing indication is ultrasound abnormality, amniocentesis and karyotype/microarray should be considered. © 2014 John Wiley & Sons, Ltd.

Expression of inhibin/activin proteins and receptors in the human hypothalamus and basal forebrain.

The inhibin/activin family of proteins is known to have a broad distribution of synthesis and expression in many species, as well as a variety of functions in reproductive and other physiological systems. Yet, our knowledge regarding the production and function of inhibin and activin in the central nervous system is relatively limited, especially in humans. The present study aimed to explore the distribution of inhibin/activin protein subunits and receptors in the adult human brain. The human hypothalamus and surrounding basal forebrain was examined using post-mortem tissues from 29 adults. Immunocytochemical studies were conducted with antibodies directed against the inhibin/activin α, ßA, and ßB subunits, betaglycan and the activin type IIA and IIB receptors. An immunoassay was also utilised to measure dimeric inhibin A and B levels in tissue homogenates of the infundibulum of the hypothalamus. Robust ßA subunit immunoreactivity was present in the paraventricular, supraoptic, lateral hypothalamic, infundibular, dorsomedial and suprachiasmatic nuclei of the hypothalamus, in the basal ganglia, and in the nucleus basalis of Meynert. A similar staining distribution was noted for the ßB subunit, betaglycan and the type II receptor antibodies, whereas α subunit staining was not detected in any of the major anatomical regions of the human brain. Inhibin B immunoreactivity was present in all tissues, whereas inhibin A levels were below detectable limits. These studies show for the first time that the inhibin/activin protein subunits and receptors can be co-localised in the human brain, implicating potential, diverse neural functions.

First assessment of menstrual cycle function and reproductive endocrine status in Samoan women.

BACKGROUND: American Samoa and Samoa are now characterized by one of the world's highest levels of adult overweight and obesity. Our objective was to investigate patterns of menstrual cyclicity reported by Samoan women and examine the relationship to adiposity and select hormone levels. METHODS: A cross-sectional analysis was performed among Samoan women, aged 18-39 years (n = 322), using anthropometric and biomarker measures of adiposity and reproductive health, including insulin, adiponectin, testosterone, sex hormone-binding globulin, free androgen index (FAI) and mullerian-inhibiting substance (MIS). Menstrual regularity was assessed from self-reported responses. Multivariable models were estimated to adjust for potential confounding of the associations between menstrual patterns and other measures. RESULTS: A high proportion of the women (13.7%) reported oligomenorrhea or amenorrhea (OM/AM). More than three-quarters, 80.7%, of women were either overweight or obese, using Polynesian-specific criteria, and OM/AM was significantly associated with higher BMI. Abdominal circumference and insulin levels were significantly higher, and adiponectin levels were lower, in those who reported OM/AM versus regular menstruation. The FAI was higher in women with increased BMI. MIS levels declined with age, more slowly in those reporting OM/AM. CONCLUSIONS: Self-reported OM/AM was associated with an elevated BMI, abdominal adiposity and serum insulin, and with reduced adiponectin levels. These findings support a high rate of metabolic syndrome, and perhaps PCOS and reproductive dysfunction, among Samoan women.

Maintaining quality assurance for sonographic nuchal translucency measurement: lessons from the FASTER Trial.

OBJECTIVE: To evaluate nuchal translucency measurement quality assurance techniques in a large-scale study. METHODS: From 1999 to 2001, unselected patients with singleton gestations between 10 + 3 weeks and 13 + 6 weeks were recruited from 15 centers. Sonographic nuchal translucency measurement was performed by trained technicians. Four levels of quality assurance were employed: (1) a standardized protocol utilized by each sonographer; (2) local-image review by a second sonographer; (3) central-image scoring by a single physician; and (4) epidemiological monitoring of all accepted nuchal translucency measurements cross-sectionally and over time. RESULTS: Detailed quality assessment was available for 37 018 patients. Nuchal translucency measurement was successful in 96.3% of women. Local reviewers rejected 0.8% of images, and the single central physician reviewer rejected a further 2.9%. Multivariate analysis indicated that higher body mass index, earlier gestational age and transvaginal probe use were predictors of failure of nuchal translucency measurement and central image rejection (P = 0.001). Epidemiological monitoring identified a drift in measurements over time. CONCLUSION: Despite initial training and continuous image review, changes in nuchal translucency measurements occur over time. To maintain screening accuracy, ongoing quality assessment is needed.

Inhibin A measurement using an automated assay platform.

BACKGROUND: Second-trimester measurement of maternal serum inhibin A is widely used for Down syndrome screening. To date, only a manual enzyme-linked immunosorbent assay (ELISA) produced by Diagnostic Systems Laboratories, Inc (DSL) has been available. The objective of this study was to compare the DSL assay with a new automated assay produced by Beckman Coulter, Inc (Access). METHODS: Residual serum samples from 570 women, who were receiving routine screening for Down syndrome, were retrieved from storage. The Access assay sensitivity, linearity and reproducibility were determined and a method comparison was performed. Inhibin A levels were measured using both assays. Twenty samples from women with confirmed Down syndrome pregnancy were also tested. RESULTS: The Access assay had coefficients of variation of less than 10% across the range of values tested, and a sensitivity below 1 pg/mL. The DSL and Access inhibin A assay values were highly correlated (r = 0.961, r(2) = 0.923), with no apparent outliers. Inhibin A values from the Access assay were a constant 23% lower (95% CI 1-41%) than corresponding values from the DSL assay. Median values from 15 to 20 completed weeks' gestation were computed and found to be consistent with expectations. The weight-adjusted multiples of the median (MoM) levels in the unaffected pregnancies fit a log Gaussian distribution well between at least the 5th and 95th percentiles with corresponding log standard deviations of 0.1960 and 0.1919 for DSL and Access, respectively. CONCLUSIONS: With median inhibin A levels appropriately calculated for the Access assay, Down syndrome screening performance is expected to be comparable to that obtained with the manual DSL assay.

First- and second-trimester Down syndrome screening markers in pregnancies achieved through assisted reproductive technologies (ART): a FASTER trial study.

OBJECTIVE: To determine whether first- and second-trimester Down syndrome screening markers and screen-positive rates are altered in pregnancies conceived using assisted reproductive technologies (ARTs). METHODS: ART pregnancies in the multicenter FASTER trial were identified. Marker levels were evaluated for five types of ART: in vitro fertilization with ovulation induction (IVF-OI), IVF with OI and egg donation (IVF-OI-ED), IVF with ED (IVF-ED), and intrauterine insemination with OI (IUI-OI) or without OI (IUI). Each group was compared to non-ART controls using Mann-Whitney U analysis. RESULTS: First-trimester marker levels were not significantly different between ART and control pregnancies, with the exception of reduced PAPP-A levels in the IUI-OI group. In contrast, second-trimester inhibin A levels were increased in all ART pregnancies, estriol was reduced and human chorionic gonadotropin (hCG) was increased in IVF and IUI pregnancies without ED, and alpha-fetoprotein (AFP) was increased in ED pregnancies. Second-trimester screen-positive rates were significantly higher than expected for ART pregnancies, except when ED was used. CONCLUSIONS: These data show that ART significantly impacts second-, but not first-, trimester markers and screen-positive rates. The type of adjustment needed in second-trimester screening depends on the particular type of ART used.

The influence of depression, body mass index, and smoking on serum inhibin B levels in late reproductive-aged women.

CONTEXT: Women experiencing depression have difficult psychosocial functioning, and recent data suggest an earlier onset of menopause. Understanding the biological mechanism for the impairment of reproductive function associated with depression is important. OBJECTIVE: The objective of the study was to determine whether a lifetime history of depression is associated with reduced ovarian reserve as reflected in serum levels of the granulosa cell product, inhibin B. DESIGN: Residual serum samples from a subset of patients in the Harvard Study of Cycles and Moods were collected. SETTING: Patients were recruited from seven Boston-area communities. PATIENTS: Women with or without a history of major depression, based on structured clinical interviews for Diagnostic and Statistical Manual of Mental Disorders, fourth edition, were enrolled. A subset of patients who had provided an early follicular phase blood specimen at study enrollment and two or more other samples over the first 18-month period of follow-up were included. INTERVENTION: There were no interventions. MAIN OUTCOME MEASURE: Serum inhibin B levels were measured. RESULTS: Serum FSH levels were higher in women with a history of depression, whereas inhibin B levels did not differ between groups. Body mass index and age were significantly and inversely related to serum inhibin B levels. Smoking history was noted, for the first time, to have a significant negative association with inhibin B levels. CONCLUSIONS: Smoking has a direct negative effect on ovarian reserve, as suggested by decreased serum inhibin B levels. In contrast, effects of depression on the reproductive axis may occur at the level of the pituitary and/or hypothalamus rather than at the gonadal level, as suggested by increased serum FSH levels.

Mullerian inhibiting substance levels at the time of HCG administration in IVF cycles predict both ovarian reserve and embryo morphology.

BACKGROUND: Pre-antral and early antral follicles secrete Müllerian inhibiting substance (MIS), suggesting that MIS may directly reflect ovarian reserve. Since little is known about how ovarian reserve affects oocyte quality, we attempt here to assess the predictive value of MIS on embryo morphology and IVF outcome. To do so, we measured MIS at the time of HCG administration 36 h prior to oocyte retrieval. METHODS: A total of 257 patients undergoing IVF were prospectively recruited. We measured MIS levels by enzyme-linked immunosorbent assay at the time of HCG, and compared the MIS values to day 3 FSH levels in the prediction of embryo morphology and IVF outcome. RESULTS: The distribution of MIS levels was skewed, with a median of 2.7 ng/ml (range 0 to 28.5 ng/ml). MIS values at the time of HCG administration inversely correlated with basal FSH levels (P = 0.002), and both correlated significantly with patient age, number of mature follicles, number of oocytes retrieved and serum estradiol levels. MIS levels correlated significantly with a greater number of 6-cell embryos and better embryo morphology score, while basal FSH levels did not correlate with these outcome variables. MIS levels > or =2.7 ng/ml portended improved oocyte quality as reflected in a higher implantation rate (P = 0.001) and a trend toward a better clinical pregnancy rate (P = 0.084). CONCLUSIONS: MIS levels seem to predict not only ovarian reserve, but also embryo morphology. Measurement of MIS at the time of HCG administration may, therefore, in the future improve management of patients undergoing treatments with assisted reproductive technology.

Inhibins and activins in human fetal abnormalities.

To date, the only routine clinical application of inhibin or activin measurement in testing for fetal abnormalities has been the use of inhibin A in prenatal screening for trisomy 21 (Down syndrome). Second trimester maternal serum levels of inhibin A are, on average, two-fold higher in Down syndrome than in unaffected pregnancies. Although the biology of altered second trimester maternal serum analyte levels in Down syndrome pregnancy cannot yet be explained, it seems that fetal products tend to be decreased, while placental products tend to be increased. This pattern holds true for inhibin A because maternal serum levels appear to be derived from placental rather than fetal sources. Therefore, the measurement of inhibins and activins in maternal fluids, although clinically useful and relatively easy to obtain, may not be helpful in studying their role in human fetal development. Studies in transgenic mice indicate a role for activin, follistatin, and activin receptor type IIA in development of the palate and craniofacial region. Cleft palate is a common birth defect and is associated with serious feeding and respiratory complications in newborns. We have begun to investigate the potential role of activin in human craniofacial development by examining the spatial and temporal expression of inhibin/activin subunits, follistatin and the activin receptors in the fetal palate. Palate tissues were collected at autopsy from fetuses ranging in gestational age from 9 to 42 weeks, and 8 week embryonic tissues were also examined. Tissues were either stored in paraffin for immunocytochemistry or were frozen for RT-PCR examination of the expression of inhibin/activin proteins or mRNAs, respectively. To date, betaA subunit, follistatin, and activin receptor, but not alpha and betaB subunit, mRNAs are present in palate tissues and inhibin/activin betaA immunoreactivity has been consistently observed in developing bone. Expression of the activin A subunit and its receptors in the human fetal palate are consistent with a developmental role. Studies are ongoing to determine whether altered activin biosynthesis is associated with cleft palate. Future studies of fetal tissues may help to elucidate other roles for the TGF-beta family in human development.

Molecular weight forms of inhibin A, inhibin B and pro-alphaC in maternal serum, amniotic fluid and placental extracts of normal and Down syndrome pregnancies.

BACKGROUND: Inhibin A, an established prenatal marker of Down syndrome (DS), exists in the maternal circulation in a number of isoforms. The present study explored whether specific inhibin A isoforms may be selectively increased in DS, offering the prospect of improved marker performance. METHODS: Second trimester maternal serum, placental extracts and amniotic fluid (AF) pools from both normal and DS pregnancies were fractionated by a combined immunoaffinity (IA) chromatography, preparative polyacrylamide gel electrophoresis (Prep-PAGE) and electroelution procedure. Inhibins A, B and pro-alphaC were determined in the eluted fractions by specific enzyme-linked immunosorbent assays (ELISAs) and the profiles of immunoactivity (IA) characterized in terms of molecular weight (MW) and percentage recovery. RESULTS: The MW patterns of inhibin A and pro-alphaC in maternal serum and AF were similar between DS and control pregnancies, both showing peaks between 25-40 k and approximately 65 k. AF contained, in addition, a higher proportion of <30 k inhibins A and B, and <25 k pro-alphaC forms. There were large differences in the inhibin forms present in DS placentae, with more 70 k and less 30-40 k inhibin A than in controls. CONCLUSIONS: The present data suggest that the processing, cleavage or secretion of inhibin MW forms by the DS placenta differs from normal. However, these differences are not reflected in maternal serum and so improvements in serum screening will not be afforded by measuring specific inhibin A isoforms.

Molecular analysis of inhibin A and activin A subunit gene loci in epithelial ovarian cancer.

Inhibin A (alpha-betaA) and activin A (betaA-betaA) are biochemically similar proteins that generally have opposite biologic functions. For example, while inhibin (alpha subunit) is proposed to be a tumor suppressor in some types of ovarian cancer, activin appears to stimulate tumor development. Previous reports suggest that a loss of alpha inhibin subunit expression and elevated serum activin levels are associated with human epithelial ovarian cancer (EOC). Our objective was to examine the alpha inhibin subunit gene locus on chromosome 2q for evidence of loss of heterozygosity (LOH) in cases of EOC and to correlate these results with serum activin A levels measured in the same patients. Ovarian tumor and matched healthy tissue samples were collected from 22 women with EOC. DNA was extracted and subjected to PCR analysis using 10 primers, seven from chromosome 2q (alpha inhibin subunit locus) and, as a control, three from chromosome 7p (inhibin/activin betaA subunit). In addition, each patient had a preoperative serum activin A measurement using an ELISA assay. One (1/22) case of EOC demonstrated LOH for one microsatellite marker at the alpha inhibin gene locus. Thirty-six percent (8/22) of patients had an activin A level that was increased above the normal range. We conclude that loss of heterozygosity at the inhibin/activin alpha subunit locus is not frequently associated with EOC. More direct molecular analyses of the inhibin and activin genes are warranted to rule out mutations in cases of epithelial ovarian cancer.

Pre-eclampsia with fetal growth restriction: placental and serum activin A and inhibin A levels.

Activin A (beta A beta A) and inhibin A (alpha beta A) are dimeric glycoproteins secreted from early to term pregnancy in the maternal circulation. They circulate in higher amounts in women with gestational hypertension and/or pre-eclampsia, the most important gestational diseases also causing fetal growth restriction (FGR). Since no data are available in patients with pre-eclampsia and superimposed FGR, by using two-site immunoassays we evaluated serum activin A and inhibin A levels in serum samples collected from: healthy normotensive pregnant controls (n = 42); and women with pre-eclampsia with (n = 19) or without superimposed FGR (n = 21). In addition, by quantitative reverse transcriptase-polymerase chain reaction the changes of alpha- and beta A-subunit mRNA expression in placentas collected from healthy controls (n = 7) and pre-eclamptic pregnancies with (n = 6) or without (n = 6) superimposed FGR was also investigated. Activin A and inhibin A serum levels were significantly higher in pre-eclampsia, and the presence of FGR did not significantly modify these concentrations. Similarly, inhibin-subunit mRNA levels in placentas from pre-eclampsia were significantly higher than in controls, and FGR did not significantly affect this expression. The present data suggest that the increased placental expression of inhibin subunit mRNAs is part of the mechanism leading to increased serum activin A and inhibin A levels.

Dynamics of inhibin subunit and follistatin mRNA during development of normal and polycystic ovary syndrome follicles.

To further explore the developmental dynamics and possible roles of inhibin, activin, and follistatin in the development of human antral follicles as well as the relationship between mRNA and protein levels of these hormones within follicles, quantitative competitive RT-PCR assays were established to determine mRNA levels for the inhibin/activin subunits and both follistatin splice variants. Granulosa cell RNA was obtained by transvaginally aspirating follicles (6-23 mm) from carefully characterized normal women at different times of the follicular phase. alpha- and beta(A)-subunit mRNA levels increased significantly with follicle diameter (r = 0.56; P < 0.01 and r = 0.45; P < 0.05, respectively) and follicle maturity (r = 0.65; P < 0.001 and r = 0.58; P < 0.01, respectively), but beta(B) mRNA levels, which were at least 10-fold lower than levels of the other subunits, showed no relationship to size or maturity. Both follistatin 315 and 288 transcripts were detected in granulosa cells, but neither follistatin transcript varied significantly across the range of follicle sizes analyzed. In addition, granulosa cells contained three follistatin 315 mRNA transcripts for each follistatin 288 transcript, and the follistatin 315/288 ratio did not vary with follicle size. alpha-Subunit mRNA levels were positively associated with dimeric inhibin A protein in human follicular fluid from the same follicle aspirates (r = 0.71; P < 0.001). Similarly, beta(A)-subunit mRNA was associated with inhibin A (r = 0.59; P < 0.01), and beta(B) mRNA was associated with inhibin B (r = 0.67; P < 0.005) in these samples. Thus, the increase in inhibin subunit transcription and protein synthesis with follicle size suggests that inhibin biosynthesis might be important for continued development of the dominant follicle. To explore this hypothesis further, we compared mRNA levels for each of these transcripts in follicles obtained from six polycystic ovary syndrome patients (eight follicles) and compared the results to those from a group (n = 5) of normal follicles matched for mean diameter. Comparisons were also performed for a subset of polycystic ovary syndrome follicles (n = 5) matched for diameter and size range with the normal group. alpha-Subunit mRNA levels were 16-fold lower in both polycystic ovary syndrome follicle groups relative to size-matched normal follicles (P < 0.02), whereas beta(A)-subunit mRNA was significantly lower only when all polycystic ovary syndrome follicles were compared. beta(B)-Subunit and follistatin mRNA levels and the follistatin 315/288 ratio were not statistically different for any group. These results suggest that insufficient production of inhibin alpha and possibly beta(A)-subunits, but not follistatin, is associated with follicular arrest in polycystic ovary syndrome follicles.

Maternal serum levels of type I and type III procollagen peptides in pre-eclamptic pregnancy.

OBJECTIVE: To compare maternal serum levels of two markers of collagen synthesis, procollagen I carboxy-terminal peptide (PICP) and procollagen III amino-terminal peptide (PIIINP), in patients with pre-eclampsia and in controls. METHODS: PICP and PIIINP were measured by radioimmunoassay in maternal serum samples from patients diagnosed with pre-eclampsia at 32 weeks' gestation or later and in controls from the same period of gestation. For PICP, 37 cases and 36 controls were studied; for PIIINP, 12 cases and 19 controls were studied. RESULTS: Both PICP and PIIINP levels were significantly elevated in patients with pre-eclampsia. PICP and PIIINP levels were, on average, 20% and 80% higher than in controls, respectively. CONCLUSIONS: These results are in agreement with previous findings that maternal serum levels of PICP and PIIINP are mildly elevated in patients with pre-eclampsia. These markers are unlikely to be useful in the prediction of pre-eclampsia.

Clinical validation of a new dimeric inhibin-A assay suitable for second trimester Down's syndrome screening.

OBJECTIVE: To compare the Down's syndrome screening performance of a simplified dimeric inhibin-A assay (Diagnostic Systems Laboratories (DSL)) with an assay whose clinical utility has been established (Serotec). SETTING: A case control set consisting of 51 Down's syndrome and 245 matched unaffected pregnancies collected as part of an earlier multicentre cohort study. METHODS: Sera were assayed for dimeric inhibin-A using the DSL assay and Serotec reference assay. Data analysis included a method comparison of mass values, fit of data to a logarithmic Gausian distribution, and determination of detection and false positive rates. In addition, 234 fresh sera were assayed using the simplified method. RESULTS: The two assays showed a high correlation (r = 0.93) but average concentrations of the DSL assay were 48% higher. However, the differences were basically proportional over the range of values important for screening. The detection rate was essentially equivalent for the DSL assay whether analysed univariately or in combination with other markers (for example, 79% v 75% at a 5% false positive rate for the DSL and Serotec assays for the combination of alpha fetoprotein, unconjugated oestriol, human chorionic gonadotrophin, and dimeric inhibin-A, respectively). The 234 dimeric inhibin-A values measured on fresh sera fitted a logarithm Gaussian distribution for the DSL assay, as indicated by the fit to a probability plot. CONCLUSIONS: The Down's syndrome screening performance of a simplified dimeric inhibin-A immunoassay was equivalent to a more labour intensive established dimeric inhibin-A assay.

High maternal serum inhibin A levels following the loss of one fetus in a twin pregnancy.

Inhibin A levels are elevated in the second trimester of pregnancies affected with fetal Down syndrome, on average, two times the level in unaffected pregnancies. Inhibin A levels are also two times higher in twin than in singleton pregnancies. Prenatal serum screening using inhibin A levels as a second trimester marker began at the Women and Infants Hospital in March 1998. We describe a case of a 17-year-old woman thought to have had a complete spontaneous abortion of a twin pregnancy but later found to be continuing the pregnancy with a single fetus. Routine second trimester prenatal serum screening revealed an extremely elevated inhibin A level of 39 MoM (multiples of the median). The patient delivered an apparently healthy female infant at 41 weeks of gestation. Therefore, inhibin A may be extremely elevated in the second trimester of a twin pregnancy after the loss of one fetus and this increased inhibin A level does not have any obvious adverse maternal or fetal effects.

Inhibin B response to EFORT is associated with the outcome of oocyte retrieval in the subsequent in vitro fertilization cycle.

OBJECTIVE: To examine whether the magnitude of the rise in inhibin B levels after gonadotropin challenge is associated with subsequent response to ovarian stimulation during IVF. DESIGN: Inhibin B serum levels after EFORT (exogenous follicle-stimulating hormone ovarian reserve test). SETTING: Academic clinical practice. PATIENT(S): Serum samples from women who had undergone ovarian reserve screening with FSH in preparation for IVF. Thirteen of these women had a poor response in IVF (canceled cycle for low estradiol and/or no oocytes retrieved), and 19 had a good response (> or =10 oocytes retrieved). INTERVENTION(S): EFORT test. MAIN OUTCOME MEASURE(S): Baseline (day 3) serum E(2) (bE(2)), FSH (bFSH), and inhibin B (bInhB) levels and inhibin B and E(2) levels 24 hours after EFORT (DeltaInhB and DeltaE(2)). RESULT(S): The mean bInhB and DeltaInhB levels were significantly higher in good vs. poor responders. The odds ratio of having a good response for women with a DeltaInhB of 202 pg/mL was 51.8 times (95% CI = 6.1-1,244) the corresponding odds for women with a DeltaInhB of 49 pg/mL. As expected, DeltaE(2) was also significantly higher in good vs. poor responders; however, combination of DeltaE(2) plus DeltaInhB did not improve the odds for predicting IVF response. CONCLUSION(S): Our data suggest that DeltaInhB after EFORT may provide a method for predicting ovarian response to hyperstimulation in a subsequent IVF cycle.