Anogenital distance in newborn daughters of women with polycystic ovary syndrome indicates fetal testosterone exposure.

Polycystic ovary syndrome (PCOS) affects ~7% of reproductive age women. Although its etiology is unknown, in animals, excess prenatal testosterone (T) exposure induces PCOS-like phenotypes. While measuring fetal T in humans is infeasible, demonstrating in utero androgen exposure using a reliable newborn biomarker, anogenital distance (AGD), would provide evidence for a fetal origin of PCOS and potentially identify girls at risk. Using data from a pregnancy cohort (The Infant Development and Environment Study), we tested the novel hypothesis that infant girls born to women with PCOS have longer AGD, suggesting higher fetal T exposure, than girls born to women without PCOS. During pregnancy, women reported whether they ever had a PCOS diagnosis. After birth, infant girls underwent two AGD measurements: anofourchette distance (AGD-AF) and anoclitoral distance (AGD-AC). We fit adjusted linear regression models to examine the association between maternal PCOS and girls' AGD. In total, 300 mother-daughter dyads had complete data and 23 mothers reported PCOS. AGD was longer in the daughters of women with a PCOS diagnosis compared with daughters of women with no diagnosis (AGD-AF: ß=1.21, P=0.05; AGD-AC: ß=1.05, P=0.18). Results were stronger in analyses limited to term births (AGD-AF: ß=1.65, P=0.02; AGD-AC: ß=1.43, P=0.09). Our study is the first to examine AGD in offspring of women with PCOS. Our results are consistent with findings that women with PCOS have longer AGD and suggest that during PCOS pregnancies, daughters may experience elevated T exposure. Identifying the underlying causes of PCOS may facilitate early identification and intervention for those at risk.

Initial IVF-ET experience with assisted hatching performed 3 days after retrieval followed by day 5 embryo transfer.

OBJECTIVE: To report our initial IVF-ET experience combining assisted hatching performed 3 days after oocyte retrieval with day 5 embryo transfer (ET). DESIGN: Retrospective review of 110 consecutive IVF cycles not involving donor oocytes, including 16 cycles that involved assisted hatching performed 3 days after oocyte retrieval in combination with day 5 ET. SETTING: Academic teaching hospital IVF center. PATIENT(S): Eighty-six consecutive IVF patients undergoing ET. INTERVENTION(S): Assisted hatching using acid Tyrode's solution performed 3 days after oocyte retrieval in selected cases in combination with day 3 or 5 ETs. MAIN OUTCOME MEASURE(S): Clinical pregnancy rate per ET. RESULT(S): Of the 16 women undergoing day 5 ET following day 3 assisted hatching, 14 had a clinical pregnancy. These included 11 ongoing/delivered singletons and 2 ongoing/delivered twin pregnancies, neither of which was monochorionic. These clinical and ongoing/delivered pregnancy rates compared very favorably with those of 54% and 46%, respectively, for the 35 patients undergoing day 5 ETs without assisted hatching, even though the latter group appeared to be better IVF candidates based on the prognostic factors commonly used to predict success. CONCLUSION(S): Our experience suggests that day 3 assisted hatching followed by day 5 ET may be a useful combination in selected patients. Although not seen in our small series, an increased risk of monochorionic pregnancies remains a theoretical concern when such a combination is used, since both assisted hatching and blastocyst transfers have been independently linked to an increased risk in some reports.

The use of androgens in menopause.

Recent increase in the potential role for androgen supplementation in the menopause, as well as the availability of nontraditional, over-the-counter food supplements containing DHEA, currently touted for postmenopausal health, have raised the need for clinicians to have a working knowledge of both potential benefits and risks of androgen replacement as a supplement to traditional hormone replacement therapy. There is compelling evidence that androgen levels are reduced after bilateral oophorectomy. The degree of androgen reduction after natural menopause may be less, and the onset of this decrease more gradual in this population. A decrease in androgen levels has been proposed as one etiology for decreased libido, and there is some evidence to support androgen use in oophorectomized women suffering from diminished libido. Such evidence is mixed, however, in naturally menopausal women. Androgen replacement may provide additional relief of menopausal symptoms in some patients, but this evidence is also inconsistent. Initial studies seem to support a perceived enhancement in psychological well-being, but confirmatory, long-term studies are still needed. Available evidence suggests a positive impact on bone density with the use of some androgen preparations, but no consistent benefit from DHEA has been demonstrated. Although androgen therapy can induce decreases in HDL cholesterol levels, the clinical impact of this is not yet known. Currently, there is little support for the routine use of androgen supplementation in the menopause. Additionally, a number of adverse events may be associated with androgen use. Careful patient selection, with comprehensive evaluation to sort out other possible medical or psychological conditions, should be undertaken before the initiation of androgen replacement. Currently available preparations are limited in number and flexibility in dosing, but there is ongoing effort to develop new delivery systems and therapeutics so that options available in the future may allow for enhanced availability and efficacy.

An update on the classification of endometriosis.

The challenge of creating a satisfactory classification of endometriosis remains to be answered. The ability of the current classification schemes to predict pregnancy outcome or to aid in the management of pelvic pain is recognized to be inadequate. Further revisions of the current classification scheme are anticipated as the understanding of how endometriosis contributes to infertility and pelvic pain evolves. In any revision of the classification system, use of empirically derived weights and breakpoints to define disease stages based on outcome data in larger clinical trials should be attempted. It is also possible that additional factors such as CA-125 level or lesion characteristics may be shown to play an important role in prognosis. If so, these will need to be accounted for in the classification scheme. Careful and consistent use of the recommendations of the American Society for Reproductive Medicine classification of endometriosis subcommittee should allow for collection of data for use in further revisions. It is quite possible that a classification scheme that is designed to predict outcome with respect to pregnancy may be totally inadequate in assessing patients who have endometriosis and pelvic pain. Factors found to be important in the assessment of pelvic pain may be different from those involved with the pathophysiology of endometriosis and infertility. The AFS form suggested for use in the management of endometriosis in the presence of pelvic pain allows for recording of variables such as depth of invasion, histology, as well as documenting adjunct investigations and preoperative physical findings. Such prospective data collection and review in large centers may provide a large clinical base from which to derive empirical point scores and breakpoints in a classification scheme.

Evaluation of LH secretory dynamics during the rat proestrous LH surge.

The preovulatory luteinizing hormone (LH) surge results from the integration of complex interactions among gonadal steroids and hypothalamic and pituitary hormones. To evaluate changes in LH secretory dynamics that occur during the rat LH surge, we have 1) obtained frequently sampled serum LH concentration time series, 2) used both waveform-dependent and waveform-independent convolution analyses, and 3) independently assessed proestrous LH half-life and basal non-gonadotropin-releasing hormone (GnRH)-dependent LH secretion during the LH surge. Waveform-independent pulse analysis revealed a 24-fold increase in the maximal pulsatile LH secretory rate attained during late proestrus compared with early proestrus. A 15-fold increase was quantified for the mean LH secretory rate. In complementary analyses, we applied a measured LH half-life of 17 +/- 2.7 min and a median basal LH secretion rate of 0.0046 microgram. l-1. min-1 for convolution analysis, revealing a 16-fold increase in the mass of LH released/burst and more than sixfold rise in the amplitude of the secretory peaks. Evaluation of the approximate entropy of the LH surge profiles was performed, showing an increase in the orderliness of the LH release process during the surge. We conclude that both quantitative (mass/burst) and qualitative (approximate entropy) features of LH release are regulated during the proestrous LH surge.

Classification of endometriosis.

The evolution of classification schemes for endometriosis has continued since the 1920s, when initial attempts were made to describe endometriosis. The cause, pathophysiology, and natural history of endometriosis remain difficult to characterize. As knowledge about endometriosis increases, classification schemes will change to incorporate new ideas. Evolution of the current American Fertility Society's revised classification of endometriosis is reviewed, as well as evaluation of its use with respect to prediction of fertility and management of pelvic pain. Possible directions for classification in the future are also discussed in this article.