Basonuclin 1 deficiency is a cause of primary ovarian insufficiency.

Primary ovarian insufficiency (POI) leads to infertility and premature menopause in young women. The genetic etiology of this disorder remains unknown in most patients. Using whole exome sequencing of a large Chinese POI pedigree, we identified a heterozygous 5 bp deletion inducing a frameshift in BNC1, which is predicted to result in a non-sense-mediated decay or a truncated BNC1 protein. Sanger sequencing identified another BNC1 missense mutation in 4 of 82 idiopathic patients with POI, and the mutation was absent in 332 healthy controls. Transfection of recombinant plasmids with the frameshift mutant and separately with the missense mutant in HEK293T cells led to abnormal nuclear localization. Knockdown of BNC1 was found to reduce BMP15 and p-AKT levels and to inhibit meiosis in oocytes. A female mouse model of the human Bnc1 frameshift mutation exhibited infertility, significantly increased serum follicle-stimulating hormone, decreased ovary size and reduced follicle numbers, consistent with POI. We report haploinsufficiency of BNC1 as an etiology of human autosomal dominant POI.

Maternal and Live-birth Outcomes of Pregnancies following Assisted Reproductive Technology: A Retrospective Cohort Study.

This study was carried out to explore associations between assisted reproductive technology (ART) and maternal and neonatal outcomes compared with similar outcomes following spontaneously conceived births. We conducted a retrospective cohort study of pregnancies conceived by ART (N = 2641) during 2006-2014 compared to naturally conceived pregnancies (N = 5282) after matching for maternal age and birth year. Pregnancy complications, perinatal complications and neonatal outcomes of enrolled subjects were investigated and analysed by multivariate logistic regression. We found that pregnancies conceived by in vitro fertilization (IVF) were associated with a significantly increased incidence of gestational diabetes mellitus, gestational hypertension, preeclampsia, intrahepatic cholestasis of pregnancy, placenta previa, placental abruption, preterm premature rupture of membranes, placental adherence, postpartum haemorrhage, polyhydramnios, preterm labour, low birth weight, and small-for-date infant compared with spontaneously conceived births. Pregnancies conceived by intracytoplasmic sperm injection (ICSI) showed similar elevated complications, except some of the difference narrowed or disappeared. Singleton pregnancies or nulliparous pregnancies following ART still exhibited increased maternal and neonatal complications. Therefore, we conclude that pregnancies conceived following ART are at increased risks of antenatal complications, perinatal complications and poor neonatal outcomes, which may result from not only a higher incidence of multiple pregnancy, but also the manipulation involved in ART processes.

Association of serum and follicular fluid leptin concentrations with granulosa cell phosphorylated signal transducer and activator of transcription 3 expression in fertile patients with polycystic ovarian syndrome.

OBJECTIVE: Our objective was to evaluate whether polycystic ovarian syndrome (PCOS)-associated infertility is related to alterations of leptin, leptin receptor (Ob-R), and the phosphorylated signal transducer and activator of transcription 3 (p-STAT3)/suppressor of cytokine signal 3 (SOCS3) system in the ovary. DESIGN AND SETTING: A case-control study was conducted in a university hospital. PATIENTS: Thirty-one infertile PCOS women with oligoovulation plus polycystic ovarian morphology and 79 infertile women with tubal blockage (control) participated in the study. The subjects were stratified according to in vitro fertilization outcomes: successful and failed subgroups. METHODS: Serum and follicular fluid (FF) leptin levels were measured with ELISA. RT-PCR and Western blotting were performed to assess expression of mRNA encoding leptin and Ob-R and proteins of p-STAT3 and SOCS3 in granulosa cells (GCs). RESULTS: Leptin levels in serum and FF of PCOS women were significantly higher than those of control (P < 0.01). There were no significant differences in expression of leptin mRNA and short and long Ob-Rs between PCOS and control (P > 0.05). The p-STAT3 level was decreased in PCOS compared with control (P < 0.01), whereas SOCS3 remained significantly unchanged (P > 0.05). Further analysis showed that serum and FF leptin levels were significantly higher, whereas p-STAT3 in GCs was lower in the failed subgroup of PCOS than those in the successful subgroup of PCOS (P < 0.05). CONCLUSION: Hyperleptinemia and high FF leptin are important pathologies of PCOS with infertility. Lower levels of p-STAT3 in GCs may be related to ovarian leptin resistance and fecundity in PCOS women. Relatively high serum and FF leptin and low p-STAT3 in GCs may account for decreased fertilization, implantation, and pregnancy rates of in vitro fertilization in PCOS women.

[Outcome of in vitro fertilization-embryo transfer in treatment of polycystic ovarian syndrome].

OBJECTIVE: To evaluate the outcome of in vitro fertilization embryo transfer (IVF-ET) in treatment of polycystic ovarian syndrome (PCOS) with infertility. METHODS: A retrospective analysis was performed from 52 patients with PCOS (PCOS group) and 408 cases with tubal infertility (control group). Both groups underwent IVF-ET treatment from 2001 to 2004. The duration of stimulation, amps of gammaFSH, the level of serum E2, P on the day of HCG injection, the number of oocytes retrieved, the rates of fertilization, cleavage, implantation and pregnancy, the incidence of ovarian hyperstimulation syndrome (OHSS) and cancelled rate of ET were compared between the two groups. RESULT: The duration of stimulation and amps of gammaFSH were not significantly different between the two groups. The concentration of serum E2, P on the day of HCG injection, the numbers of oocytes retrieved and cleavaged embryos were significantly higher in PCOS group (P <0.01, <0.05). Fertilization rate was significantly lower in PCOS group (P <0.01). The implantation, pregnancy and miscarriage rates per ET were not statistically significant. The OHSS rates and cancelled rates of ET were higher in PCOS group (P <0.01). CONCLUSION: Women with PCOS have a lower fertilization rate compared with those with tubal-factor fertility during IVF-ET. However, more oocytes are recovered and the preimplanted embryo has a normal chance of implantation leading to similar pregnancy rates. The OHSS rates and cancelled rates of ET are higher in PCOS because of a greater number of oocytes developed and a higher level of E2.

Resistin levels of serum and follicular fluid in non-obese patients with polycystic ovary syndrome during IVF cycles.

OBJECTIVES: To measure serum and follicular resistin, steroids hormone levels in women with PCOS (polycystic ovary syndrome) (BMI (body mass index)<25 kg/m(2)), to assess possible correlations of resistin to hormonal and metabolic parameters and to analyze the clinical outcomes of in vitro fertilization-embryo transfer (IVF-ET) in women with PCOS and tubal infertility. STUDY DESIGN: We analyzed the clinical outcomes of IVF-ET in women with PCOS (BMI<25 kg/m(2)) and tubal infertility during the years 2002 to 2004 and compared the serum and follicular fluid resistin levels, estradiol (E(2)), progesterone (P), testosterone (T) levels in 20 PCOS and 20 healthy, age-matched women without PCOS during IVF-stimulated cycles. The correlations between the resistin levels and the outcomes of IVF-ET were evaluated. RESULTS: No significant differences in resistin levels of either serum or follicular fluid between PCOS and control group were found. However, resistin levels in serum were higher than that in follicular fluid in both groups. Multiple regression analysis showed that resistin levels in serum did not correlate with BMI, estradiol, LH (luteinizing hormone) and insulin level in fasting blood. No significant correlations were found between follicular fluid reisistin levels and fertilization rate, implantation rate, clinical pregnancy rate or early miscarriage rate in both PCOS and control groups. CONCLUSION: Our results show that resistin does not have correlation with the hormonal and metabolic parameters as well as the outcomes of IVF. These data suggest that resistin is unlikely to be a local determinant factor in steroidogenesis and growth and maturation of oocytes during IVF-ET in lean women with PCOS.