Sleep and obstructive sleep apnea in women with infertility.

PURPOSE: Obstructive sleep apnea (OSA) is associated with polycystic ovarian syndrome (PCOS), a common cause of infertility. Understanding predictors and outcomes of OSA in women with infertility may guide treatment. METHODS: A descriptive cross-sectional survey was performed to assess OSA in women presenting to an infertility clinic using validated sleep questionnaires to assess sleep and fertility outcomes. An Infertile-C group (controls with male or tubal factors) and an Infertile-S group (unknown/other infertile causes) were analyzed to assess OSA risk and other sleep disorders (e.g., restless legs syndrome (RLS) and insomnia) with fertility outcomes (time to pregnancy, PCOS, irregular menstruation, and miscarriage). RESULTS: In 258 women, occurrences of OSA diagnosis (6%) and RLS (10%) were reported similar to women of child-bearing age in the general population. PCOS was unassociated with OSA risk. Predictors of OSA risk were BMI, insomnia symptoms, and sleep aid use. Obese women with high OSA risk were more likely to have other comorbidities (e.g., depression). In adjusted models, prior clinical OSA diagnosis was associated with miscarriage (odds ratio: 6.17 (1.24, 30.62), p = 0.026). RLS was associated with irregular menstruation (odds ratio: 3.73 (1.21, 11.53), p = 0.022). CONCLUSIONS: Similar to other populations, women with infertility and OSA risk have more health comorbidities and higher BMI and may present with insomnia symptoms. While the data are limited, this study supports the potential associations of OSA and miscarriage. Further work is needed to evaluate OSA in female infertility.

A case of female epispadias.

OBJECTIVE: To present a case of unrecognized female epispadias. DESIGN: Case report. SETTING: University-based reproductive endocrinology and fertility clinic. PATIENT(S): A 16-year-old girl with epispadias, history of mild urinary incontinence, auditory neuropathy, and functional hyperandrogenism. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Peripheral blood array-based comparative genomic hybridization. RESULT(S): The patient was referred for evaluation of excessive weight gain, secondary amenorrhea, and abnormal external genitalia. Examination under anesthesia revealed bilateral labia minora hypertrophy, bifid clitoris, and a patulous urethra, consistent with female epispadias. Hormonal evaluation showed functional hyperandrogenism, and peripheral blood array-based comparative genomic hybridization showed no chromosomal deletions or duplications. CONCLUSION(S): Female epispadias is a rare abnormality, not commonly recognized by most practitioners. The diagnosis is supported by a history of urinary incontinence and physical findings of bifid clitoris and patulous urethra. The condition can have serious physical and psychological consequences leading to a gross disruption of social function.

Effectiveness of assisted reproductive technology (ART).

OBJECTIVES: We reviewed the evidence regarding the outcomes of interventions used in ovulation induction, superovulation, and in vitro fertilization (IVF) for the treatment of infertility. Short-term outcomes included pregnancy, live birth, multiple gestation, and complications. Long-term outcomes included pregnancy and post-pregnancy complications for both mothers and infants. DATA SOURCES: MEDLINE and Cochrane Collaboration resources. REVIEW METHODS: We included studies published in English from January 2000 through January 2008. For short-term outcomes, we excluded non-randomized studies and studies where a pregnancy or live birth rate per subject could not be calculated. For long-term outcomes, we excluded studies with fewer than 100 subjects and those without a control group. Articles were abstracted for relevant details, and relative risks or odds ratios, with 95 percent confidence intervals, were calculated for outcomes of interest for each study. RESULTS: We identified 5294 abstracts and (for the three questions discussed in this draft report) reviewed 1210 full-text articles and included 478 articles for abstraction. Approximately 80 percent of the included studies were performed outside the United States. The majority of randomized trials were not designed to detect differences in pregnancy and live birth rates; reporting of delivery rates and obstetric outcomes was unusual. Most did not have sufficient power to detect clinically meaningful differences in live birth rates, and had still lower power to detect differences in less frequent outcomes such as multiple births and complications. Interventions for which there was sufficient evidence to demonstrate improved pregnancy or live birth rates included: (a) administration of clomiphene citrate in women with polycystic ovarian syndrome, (b) metformin plus clomiphene in women who fail to respond to clomiphene alone; (c) ultrasound-guided embryo transfer, and transfer on day 5 post-fertilization, in couples with a good prognosis; and (d) assisted hatching in couples with previous IVF failure. There was insufficient evidence regarding other interventions. Infertility itself is associated with most of the adverse longer-term outcomes. Consistently, infants born after infertility treatments are at risk for complications associated with abnormal implantation or placentation; the degree to which this is due to the underlying infertility, treatment, or both is unclear. Infertility, but not infertility treatment, is associated with an increased risk of breast and ovarian cancer. CONCLUSIONS: Despite the large emotional and economic burden resulting from infertility, there is relatively little high-quality evidence to support the choice of specific interventions. Removing barriers to conducting appropriately designed studies should be a major policy goal.

Sperm from mice genetically deficient for the PCSK4 proteinase exhibit accelerated capacitation, precocious acrosome reaction, reduced binding to egg zona pellucida, and impaired fertilizing ability.

The gene for proprotein convertase subtilisin/kexin-like 4 (PCSK4, previously known as PC4) is primarily transcribed in testicular spermatogenic cells. Its inactivation in mouse causes severe male subfertility. To better understand the reproductive function of PCSK4, we examined its subcellular localization in the testicular epithelium via immunohistochemistry, and on intact sperm via indirect immunofluorescence and immunoelectron microscopy. PCSK4 was detected in the acrosomal granules of round spermatids, in the acrosomal ridges of elongated spermatids, and on the sperm plasma membrane overlying the acrosome. We also investigated PCSK4 relevance for sperm acquisition of fertilizing ability by comparing wild-type and PCSK4-null sperm for their abilities in capacitation, acrosome reaction, and egg binding in vitro. PCSK4-null sperm underwent capacitation at a faster rate; they were induced to acrosome react by lower concentrations of zona pellucida; and their egg-binding ability was only half that of wild-type sperm. These sperm physiologic anomalies likely contribute to the severe subfertility of PCSK4-deficient male mice.

Role of sperm surface arylsulfatase A in mouse sperm-zona pellucida binding.

We have previously described the zonae pellucidae (ZP) binding ability of a pig sperm surface protein, P68. Our recent results on peptide sequencing of 3 P68 tryptic peptides and molecular cloning of pig testis arylsulfatase A (AS-A) revealed the identity of P68 as AS-A. In this report, we demonstrate the presence of AS-A on the mouse sperm surface and its role in ZP binding. Using anti-AS-A antibody, we have shown by immunoblotting that AS-A was present in a Triton X-100 extract of mouse sperm. The presence of AS-A on the sperm plasma membrane was conclusively demonstrated by indirect immunofluorescence, immunogold electron microscopy, and AS-A's desulfation activity on live mouse sperm. The AS-A remained on the head surface of in vivo capacitated sperm, as revealed by positive immunofluorescent staining of oviductal/uterine sperm. Significantly, the role of mouse sperm surface AS-A on ZP binding was demonstrated by dose-dependent decreases of sperm-ZP binding on sperm pretreatment with anti-AS-A IgG/Fab. Furthermore, Alexa-430 conjugated AS-A bound to mouse ZP of unfertilized eggs but not to fertilized ones, and this level of binding increased and approached saturation with increasing Alexa-430 AS-A concentrations. Moreover, in vivo fertilization was markedly decreased when mouse sperm pretreated with anti-AS-A IgG were artificially inseminated into females. All of these results designated a new function for AS-A in mouse gamete interaction.