A comprehensive study of common and rare genetic variants in spermatogenesis-related loci identifies new risk factors for idiopathic severe spermatogenic failure.

Study Question: Can genome-wide genotyping data be analysed using a hypothesis-driven approach to enhance the understanding of the genetic basis of severe spermatogenic failure (SPGF) in male infertility?

Summary Answer: Our findings revealed a significant association between SPGF and the gene and identified three novel genes (, , and ) along with 32 potentially pathogenic rare variants in 30 genes that contribute to this condition.

What Is Known Already: SPGF is a major cause of male infertility, often with an unknown aetiology. SPGF can be due to either multifactorial causes, including both common genetic variants in multiple genes and environmental factors, or highly damaging rare variants.

Immune and spermatogenesis-related loci are involved in the development of extreme patterns of male infertility.

We conducted a genome-wide association study in a large population of infertile men due to unexplained spermatogenic failure (SPGF). More than seven million genetic variants were analysed in 1,274 SPGF cases and 1,951 unaffected controls from two independent European cohorts. Two genomic regions were associated with the most severe histological pattern of SPGF, defined by Sertoli cell-only (SCO) phenotype, namely the MHC class II gene HLA-DRB1 (rs1136759, P = 1.

Common genetic variation in KATNAL1 non-coding regions is involved in the susceptibility to severe phenotypes of male infertility.

Background: Previous studies in animal models evidenced that genetic mutations of KATNAL1, resulting in dysfunction of its encoded protein, lead to male infertility through disruption of microtubule remodelling and premature germ cell exfoliation. Subsequent studies in humans also suggested a possible role of KATNAL1 single-nucleotide polymorphisms in the development of male infertility as a consequence of severe spermatogenic failure.

Objectives: The main objective of the present study is to evaluate the effect of the common genetic variation of KATNAL1 in a large and phenotypically well-characterised cohort of infertile men because of severe spermatogenic failure.

Common Variation in the PIN1 Locus Increases the Genetic Risk to Suffer from Sertoli Cell-Only Syndrome.

We aimed to analyze the role of the common genetic variants located in the locus, a relevant prolyl isomerase required to control the proliferation of spermatogonial stem cells and the integrity of the blood-testis barrier, in the genetic risk of developing male infertility due to a severe spermatogenic failure (SPGF). Genotyping was performed using TaqMan genotyping assays for three taggers (rs2287839, rs2233678 and rs62105751). The study cohort included 715 males diagnosed with SPGF and classified as suffering from non-obstructive azoospermia (NOA, = 505) or severe oligospermia (SO, = 210), and 1058 controls from the Iberian Peninsula.

Intronic variation of the SOHLH2 gene confers risk to male reproductive impairment.

Objective: To evaluate whether SOHLH2 intronic variation contributes to the genetic predisposition to male infertility traits, including severe oligospermia (SO) and different nonobstructive azoospermia (NOA) clinical phenotypes.

Design: Genetic association study.

Setting: Not applicable.

Comparison of the effect of two combinations of myo-inositol and D-chiro-inositol in women with polycystic ovary syndrome undergoing ICSI: a randomized controlled trial.

The purpose of this study was to evaluate the effect of two doses of D-chiro-inositol (DCI) in combination with Myo-inositol (MYO) in women with PCOS undergoing ICSI. This was a multicenter controlled, randomized, double-blind parallel group study with two MYO-DCI formulations for 12 weeks. The study group (SG) was administered 550 mg of MYO + 150 mg of DCI twice daily; the control group (CG) was administered 550 mg of MYO + 13.

Could the addition of hp-hMG and GnRH antagonists modulate the response in IVF-ICSI cycles?

Objective: To assess if the luteinizing hormone/human chorionic gonadotropin present in some gonadotropin formulations may be of benefit in protocols with GnRH antagonists.

Methods: Open, quasi-experimental, multicenter, prospective, parallel-controlled study compared 136 women undergoing in vitro fertilization--intracytoplasmic sperm injection after stimulation with highly purified human menopausal gonadotropin (hp-hMG) (n = 44), recombinant-follicle stimulating hormone (r-FSH) (n = 46), or a combination of both (r FSH + hp-hMG) (n = 46) following an antagonist protocol. Blood determinations were made on day 6 of stimulation and on the day of ovulation induction, with centralized analysis.

Expression of transcription factors in endometrium during natural cycles.

Purpose: The sex steroid control of the endometrial cycle is mediated by transcription factors, four of which are the estrogen and progesterone receptors, c-jun and c-fos, all expressed by the endometrium. The aim of this study was to analyze the distribution of the transcription factors in the different endometrial compartments during natural cycles.

Methods: We studied 53 reproductively-normal women, of whom 26 were in the proliferative phase and 27 in the secretory phase.

Apoptosis in human granulosa cells after induction of ovulation in women participating in an intracytoplasmic sperm injection program.

Objectives: To investigate whether analysis of granulosa cell apoptosis can be useful in assessing follicular and oocyte maturation and the regulation of granulosa cell apoptosis by follicular fluid steroids in preovulatory follicles of stimulated women.

Study Design: Apoptosis in aspirated granulosa cells (n=64) was measured using the Annexin V-affinity assay by flow cytometry. Follicular fluid steroids were determined by ELISA and RIA.