The BISTIM study: a randomized controlled trial comparing dual ovarian stimulation (duostim) with two conventional ovarian stimulations in poor ovarian responders undergoing IVF.

Study Question: Is the total number of oocytes retrieved with dual ovarian stimulation in the same cycle (duostim) higher than with two consecutive antagonist cycles in poor responders?

Summary Answer: Based on the number of total and mature oocytes retrieved in women with poor ovarian response (POR), there is no benefit of duostim versus two consecutive antagonist cycles.

What Is Known Already: Recent studies have shown the ability to obtain oocytes with equivalent quality from the follicular and the luteal phase, and a higher number of oocytes within one cycle when using duostim. If during follicular stimulation smaller follicles are sensitized and recruited, this may increase the number of follicles selected in the consecutive luteal phase stimulation, as shown in non-randomized controlled trials (RCT).

[Dydrogesterone versus micronized vaginal progesterone as luteal phase support after fresh embryo transfer in IVF].

Objectives: The objective of the study was to compare the live birth rate and miscarriage rate after fresh embryo transfer (Fresh ET) when patients are treated either with oral dydrogesterone or micronized vaginal progesterone (MVP) as luteal phase support (LPS). The vaginal route is still preferred, despite the discomfort for the patients and recent RCTs showing similar results for dydrogesterone and MVP.

Methods: All 556 consecutive Fresh ET after autologous IVF procedure, from December 2011 to March 2013 in one centre in France were included.

Live birth after in-vitro maturation of oocytes in a patient with specific ovarian insufficiency caused by long-term mitotane treatment for adrenocortical carcinoma.

Research Question: How should the fertility of a woman with persistent specific ovarian dysfunction after long-term mitotane exposure be managed?

Design: Case report. A 33-year-old woman who underwent surgery for adrenocortical carcinoma and treated with mitotane was referred for infertility. She rapidly became amenorrhoeic while taking mitotane, a condition that persisted for 5 years after cessation.

Random antral follicle count performed on any day of the menstrual cycle has the same predictive value as AMH for good ovarian response in IVF cycles.

Objective: To determine whether the predictive value of AFC for ovarian response to stimulation for IVF depends on the day of the menstrual cycle when ultrasound is performed.

Methods: 410 women undergoing their first IVF cycle were included. All the women had AFC performed twice.

Comparison of stimulated versus modified natural cycles for endometrial preparation prior to frozen embryo transfer: a randomized controlled trial.

Research Question: To compare stimulated cycle (STC) versus modified natural cycle (MNC) for endometrial preparation prior to frozen embryo transfer (FET) in terms of convenience and efficacy.

Design: Prospective, open-label, randomized controlled study including 119 patients aged 20-38 years, undergoing intra-conjugal IVF/intracytoplasmic sperm injection, having regular cycles, at least two day 2 or day 3 frozen embryos, for whom it was the first or second FET performed, randomized to either MNC (n = 59) or STC (n = 60). Monitoring consisted of ultrasound and hormonal measurements.

Kallmann syndrome with FGFR1 and KAL1 mutations detected during fetal life.

Kallmann syndrome (KS) patients carrying FGFR1 mutations can transmit the disorder to their offspring as can asymptomatic female carriers of mutations in KAL1. We describe for the first time two cases in which KS was suspected during fetal life because of the family context and malformation detection by fetal ultrasound: syndactyly or unilateral renal agenesis in subjects with respectively FGFR1 and KAL1 mutations. In relevant family history, ultrasound monitoring can detect KS associated signs before birth and thus enable neonatal diagnosis and early management.

New NOBOX mutations identified in a large cohort of women with primary ovarian insufficiency decrease KIT-L expression.

Context: Primary ovarian insufficiency (POI) is a major cause of anovulation and infertility in women. This disease affects 1% of women before 40 years, and several genetic causes have been reported.

Objective: The aim of the study was to evaluate the prevalence of NOBOX mutations in a new large cohort of women with POI and to characterize these variants and identify a NOBOX novel target gene.

Ovarian macrocysts and gonadotrope-ovarian axis disruption in premenopausal women receiving mitotane for adrenocortical carcinoma or Cushing's disease.

Context: Mitotane is an adrenolytic and anticortisolic drug used in adrenocortical carcinoma (ACC), Cushing's disease (CD), and ectopic ACTH syndrome. Its effects on the ovaries are unknown.

Objective: To evaluate the ovarian and gonadotrope effects of mitotane therapy in premenopausal women.

Testicular histological and immunohistochemical aspects in a post-pubertal patient with 5 alpha-reductase type 2 deficiency: case report and review of the literature in a perspective of evaluation of potential fertility of these patients.

Background: Testicular morphology and immunohistochemical studies have never been reported in genetically documented adult patients with 5 alpha-reductase type 2 deficiency (5α-R2 deficiency).

Case Presentation: We describe the testicular histopathology of a 17-year-old XY subject with 5α-R2 deficiency caused by the recurrent homozygous Gly115Asp loss of function mutation of the SRD5A2 gene.We also performed an immunohistochemical analysis in order to further study the relationship between seminiferous tubules structure, Sertoli cell differentiation and androgenic signaling impairment in this case.

Insulin-like peptide 3 (INSL3) in men with congenital hypogonadotropic hypogonadism/Kallmann syndrome and effects of different modalities of hormonal treatment: a single-center study of 281 patients.

Context: Insulin-like factor 3 (INSL3) is a testicular hormone secreted during fetal life, the neonatal period, and after puberty.

Objective: To measure INSL3 levels in a large series of men with congenital hypogonadotropic hypogonadism (CHH)/ Kallmann syndrome (KS), in order to assess its diagnostic value and to investigate its regulation.

Patients: We studied 281 CHH/KS patients (91 untreated, 96 receiving T, and 94 receiving combined gonadotropin therapy [human chorionic gonadotropin, hCG, and FSH]) and 72 age-matched healthy men.

Estradiol levels in men with congenital hypogonadotropic hypogonadism and the effects of different modalities of hormonal treatment.

Objective: To evaluate the degree of E2 deficiency in male congenital hypogonadotropic hypogonadism (CHH), and its response to different hormonal treatments.

Design: Retrospective and prospective studies.

Setting: Academic institution.

Congenital hypogonadotropic hypogonadism in females: clinical spectrum, evaluation and genetics.

Congenital hypogonadotropic hypogonadisms (CHH) are a well-known cause of pubertal development failure in women. In a majority of patients, the clinical spectrum results from an insufficient and concomitant secretion of both pituitary gonadotropins LH and FSH that impedes a normal endocrine and exocrine cyclical ovary functioning after the age of pubertal activation of gonadotropic axis. In exceptional but interesting cases, they can result from an elective deficit of one of the gonadotropins follicle-stimulating hormone (FSH) or luteinizing hormone (LH) by genetic anomaly of their specific ss sub-unit.

Primary amenorrhea revealing an occult progesterone-secreting ovarian tumor.

Objective: To describe a patient with primary amenorrhea revealing an occult progesterone-secreting ovarian tumor.

Design: Case report.

Setting: University medical center.

Timing of FSH administration for ovarian stimulation in normo-ovulatory women: comparison of an early or a mid follicular phase initiation of a short-term treatment.

Background: In normo-ovulatory infertile women undergoing mild ovarian stimulation out of IVF, FSH stimulation regimen must be carefully adjusted to control the number of recruited follicles and to prevent multiple pregnancies. The aim of this prospective study was to assess the effect of the timing of FSH administration (fixed dose and duration) on the number of large follicles.

Methods: Women were prospectively randomized by means of sealed envelopes to receive daily 112.

IGFBP-1 inhibits EGF mitogenic activity in cultured endometrial stromal cells.

The properties of the insulin-like growth factor-binding proteins (IGFBP-1 to 6) are not limited to modulation of IGF actions. IGFBP-1, which shares an Arg-Gly-Asp (RGD) motif in its C-terminal domain, modulates cell motility by binding to integrin alpha5beta1. The cross-talks between integrins and growth factor receptor signalling pathways are extensively documented, particularly in the case of the epidermal growth factor receptor (EGFR).

Beneficial effects of GnRH agonist administration prior to ovarian stimulation for patients with a short follicular phase.

A short follicular phase is an early clinical feature of declining reproductive competence. The shortening of the follicular phase length is related to both advanced recruitment and selection of the dominant follicle secondary to an earlier and higher FSH rise during the luteal-follicular transition, while the late follicular growth is normal. As a short follicular phase may be detrimental for reproduction, it was postulated that increasing the duration of follicular phase could improve conception rate.

[Should infertile women with polycystic ovarian syndrome be treated with metformine?].

Polycystic ovary syndrome is a frequent endocrine disorder often associated with insulin resistance and hyperinsulinaemia which may play a role in hyperandrogenism and anovulation. The use of "insulin sensitizing" agents has been suggested to reduce insulin resistance and hyperandrogenism. In that respect, the use of metformin in polycystic ovary syndrome is reviewed.

Comparison of the effectiveness of recombinant and urinary FSH preparations in the achievement of follicular selection in chronic anovulation.

In order to compare the effectiveness of urinary and recombinant FSH (rFSH) preparations in achieving the threshold of follicular growth, stimulated cycles from patients with chronic anovulation, treated with a constant dose of FSH until the emergence of a selected follicle, were retrospectively analysed. Sixty-four cycles were performed using a similar starting dose of either urinary FSH (group 1) or rFSH (group 2), which was kept constant up to the time of follicular selection, assessed on ultrasound (follicular diameter >10 mm). The results of this study showed that, while the number of selected follicles was similar, the mean daily FSH dose required to achieve the threshold of follicular selection was significantly lower in group 2 (70.

A comprehensive endocrine description of Kennedy's disease revealing androgen insensitivity linked to CAG repeat length.

Our study aims to provide a comprehensive view of the endocrine features in Kennedy's disease (KD). Twenty-two men with KD underwent detailed endocrine investigations. Clinical signs of partial androgen resistance were present in more than 80% of the patients, with gynecomastia being the most prominent.

Comparison of recombinant and urinary follicle-stimulating hormone preparations in short-term gonadotropin releasing hormone agonist protocol for in vitro fertilization-embryo transfer.

Purpose: To compare the efficiency and efficacy of two recombinant human FSH (r-FSH) and urinary (u-FSH) preparations in patients undergoing superovulation for IVF-ET using a short-term gonadotropin releasing hormone agonist (GnRH-a) (Triptorelin) protocol.

Methods: A total of 88 women undergoing IVF-ET were included in this prospective study. They were randomized to receive u-FSH (150 IU/d), follitropin-alpha (100 IU/d), or follitropin-beta (100 IU/d) for 2 days, and dosages were subsequently adjusted according to the ovarian response.