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Double ovarian stimulation (DuoStim), initially only suggested for fertility preservation in cancer patients, is now increasingly also used in routine clinical IVF, especially in poor responders. The claimed rational for this is the alleged existence of multiple follicular waves in a single intermenstrual interval, allowing for retrieval of more oocytes in a single IVF cycle. This commentary argues that this expansion of purpose lacks rationale, evidence, and follow-up. Consequently, we suggest that, unless valid clinical indications have been established, DuoStim be only subject of controlled clinical trials with appropriate experimental consents. [ABSTRACT FROM AUTHOR]

The same RCT also unequivocally showed that the mean cumulative number of oocytes, MII oocytes, and total embryos obtained from two consecutive conventional ovarian stimulations (control group) was not statistically different from the number obtained by DuoStim. Sir, We appreciate the interest of [1] in our recent opinion article that argued that the DuoStim protocol in poor responders lacks rationale, evidence, and appropriate follow-up ([6]). [Extracted from the article]

Study Question: Does Bisphenol A (BPA) impair steroid hormone production in human luteinized granulosa cells in vitro?Summary Answer: At supra-physiological concentrations, BPA alters progesterone and estradiol synthesis in vitro and significantly reduces the mRNA and protein expression levels of three genes encoding steroidogenesis enzymes.What Is Known Already: In IVF patients, the effects of BPA exposure on cycle outcome are controversial. Previous animal studies have shown that granulosa cell steroid hormone synthesis is compromised after BPA exposure, but their findings have been difficult to replicate in humans due, in part, to the low availability of discarded biological material.Study Design, Size, Duration: Luteinized granulosa cells obtained from 44 fertile and infertile patients undergoing in vitro fertilization were cultured for 48 h with different concentrations of BPA (0, 0.2, 0.02, 2.0, 20 µg/ml).Participants/materials, Setting, Methods: Culture medium and total RNA extracted from the luteinized granulosa cells were examined for estradiol and progesterone levels as well as mRNA and protein expression of steroidogenesis enzymes, using enzyme immunoassays, real-time PCR and western blots.Main Results and the Role Of Chance: Treatment of granulosa cells with 2 or 20 µg/ml BPA for 48 h resulted in significantly lower progesterone biosynthesis (P < 0.005 and <0.001, respectively). Estradiol production was significantly altered only after incubation with 20 µg/ml of BPA (P < 0.001). These concentrations also significantly reduced the mRNA levels of 3β-hydroxysteroid dehydrogenase (3β-HSD), CYP11A1 and CYP19A1 without affecting StAR and 17β-hydroxysteroid dehydrogenase mRNA expression. Similarly, 3β-HSD, CYP11A1 and CYP19A1 protein levels were reduced after administration of 20 µg/ml BPA. Lower BPA concentrations similar to, and up to 100 times, the concentrations measured in human follicular fluid, serum and urine did not alter steroidogenesis in primary granulosa cell cultures.Limitations, Reasons For Caution: This was an in vitro study investigating the effects of acute exposure (48 h) of BPA on discarded material. As such, the model may not accurately reflect the effect of BPA on the physiological events of follicular steroid hormone synthesis in vivo.Wider Implications Of the Findings: Our results show that in vitro exposure to BPA at low doses does not affect granulosa cells steroidogenesis. Combined with recent in vivo studies, these data can be reassuring but further studies are needed to assess the effects of chronic exposure to BPA on ovarian steroidogenesis.Study Funding and Competing Interests: This study was supported by grant number 1936/12 from the Israeli Science Foundation (ISF). The authors have no conflict of interest. [ABSTRACT FROM AUTHOR]

In order to determine which factors influence the large variations in sensitivity to gonadotrophins witnessed in women with polycystic ovary syndrome (PCOS), a prospective study was conducted of the correlation between basal clinical and endocrinological features and gonadotrophin requirements of 20 women with clomiphene-resistant PCOS undergoing ovulation induction. Baseline evaluation of serum concentrations of luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone, fasting insulin, insulin-like growth factor-1 (IGF-1), IGF binding protein-1 (IGFBP-1) and sex hormone-binding globulin (SHBG) were performed before administering gonadotrophin-releasing hormone agonist (GnRHa). Two weeks later, human menopausal gonadotrophin (HMG) was given in a standard individualized protocol according to ovarian response, until human chorionic gonadotrophin (HCG) was given. Serum concentrations of insulin, IGF-1, and IGFBP-1 were unaffected by GnRHa. The BMI correlated positively with insulin and inversely with IGFBP-1 serum concentrations and insulin and IGFBP-1 were inversely correlated. The amount of HMG required correlated positively with BMI and insulin concentrations and inversely with IGFBP-1 in the whole group and these correlations were maintained in the sub-group of lean women. No correlation was observed between HMG requirements and IGF-1 or other hormones. Women with hyperinsulinaemia and low IGFBP-1 concentrations required significantly more HMG. Multiple regression analysis revealed that insulin concentration is the most significant determinant of HMG requirement even when dissociated from BMI. We concluded that requirements of HMG in PCOS is not merely determined by obesity but by a cardinal role of insulin concentrations which, when high, induce, hypothetically, a hyperandrogenic intrafollicular milieu. [ABSTRACT FROM AUTHOR]

Ovarian hyperstimulation syndrome (OHSS) is the most serious, life-threatening, iatrogenic complication of ovuia-tion induction. The importance of excessive oestradiol concentrations on the day of human chorionic gonadotro-phin (HCG) administration as a predictor and factor in the pathophysiology of OHSS has been extensively studied and discussed. We present the case report of a woman with hypogonadotrophic hypogonadism who developed severe OHSS during ovulation induction with urinary human follicle stimulating hormone (FSH) and HCG in the presence of low circulating oestradiol concentrations. The implication of FSH treatment and complications in hypogonadotrophic hypogonadal patients, and the role of pre-ovulatory oestradiol concentrations in the prediction of OHSS, are discussed. [ABSTRACT FROM PUBLISHER]

The study was conducted on 144 women who experienced preclinical abortions, i.e. a transitory rise in β-human chorionic gonadotrophin (HCG) without any clinical or sonographic evidence of pregnancy, to identify the relationship between preclinical abortions and intrauterine pathology. Hysteroscopy was performed 1–2 weeks after the decline of β-HCG concentrations to negative values. Intrauterine adhesions were detected in three patients (2.1%), most of these being of the mild type. Concomitant intrauterine abnormalities, mainly uterine septa, were found in 14 (9.7%) cases. We believe that preclinical abortions do not predispose intrauterine adhesions and curettage is superfluous. An incomplete uterine septum seems to be the major factor predisposing this early pregnancy wastage. Hysteroscopy following this condition is an easy and efficient means for both identifying intrauterine pathology and excluding adhesions. [ABSTRACT FROM PUBLISHER]