Developmental epigenetic programming of adult germ cell death disease: Polycomb protein EZH2-miR-101 pathway.

AIM: The Developmental Origin of Health and Disease refers to the concept that early exposure to toxicants or nutritional imbalances during perinatal life induces changes that enhance the risk of developing noncommunicable diseases in adulthood. Patients/materials & methods: An experimental model with an adult chronic germ cell death phenotype resulting from exposure to a xenoestrogen was used. RESULTS: A reciprocal negative feedback loop involving decreased EZH2 protein level and increased miR-101 expression was identified. In vitro and in vivo knockdown of EZH2 induced an apoptotic process in germ cells through increased levels of apoptotic factors (BIM and BAD) and DNA repair alteration via topoisomerase 2B deregulation. The increased miR-101 levels were observed in the animal blood, meaning that miR-101 may be a part of a circulating mark of germ cell death. CONCLUSION: miR-101-EZH2 pathway deregulation could represent a novel pathophysiological epigenetic basis for adult germ cell disease with environmental and developmental origins.

In vitro fertilization versus conversion to intrauterine insemination in Bologna-criteria poor responders: how to decide which option?

OBJECTIVE: To compare the continuation of in vitro fertilization (IVF) with the conversion to intrauterine insemination (IUI) in cases of suboptimal ovarian response in Bologna-criteria poor responders. DESIGN: Retrospective and multicenter comparative study. SETTING: Three academic fertility centers and a fertility private clinic. PATIENT(S): Analysis of 7,176 initiated IVF cycles from January 2010 to January 2013. The 461 cycles with poor ovarian response (fewer than three follicles ≥16 mm at hCG trigger) in patients with poor response according to the Bologna criteria were included. INTERVENTION(S): Decision to pursue IVF (n = 184), convert to IUI (n = 141), or cancel cycle (n = 136) when only one or two follicles were recruited. MAIN OUTCOME MEASURE(S): Live birth, ultrasound pregnancy, and early pregnancy rates were compared depending on whether they resulted from IVF or IUI and were stratified according to patient age and the number of mature follicles at trigger. RESULT(S): Live birth rates were significantly higher for IVF patients compared with IUI conversion when two follicles were present (11.6% IVF vs. 1.6% IUI), especially for patients <40 years of age (13.1% IVF vs. 2% in IUI). In case of a monofollicular recruitment, the pregnancy outcomes were similar. CONCLUSION(S): A therapeutic strategy could therefore be to pursue IVF for women demonstrating two follicles and to convert to IUI for cycles with only one follicle if the sperm and tubal parameters are favorable.

[Male infertility due to azoospermia and in vitro fertilization assisted by ICSI. Findings based on a prospective study of our first 42 patients]. / Fécondation in vitro assistée par micro-injection (F.I.V.-I.C.S.I.). Etude prospective de 42 patients.

INTRODUCTION: Our experience of ICSI began in 1997. This study reviews our four-year experience based on 42 consecutive couples. MATERIAL AND METHOD: Between February 1997 and December 2000, 42 sterile couples due to male infertility were treated by ICSI. Surgical exploration and "open" gamete collection were proposed regardless of the predefined type of azoospermia, obstructive or non-obstructive. RESULT: Seventy one cycles were performed: ICSI used epididymal spermatozoa in 49 cycles, and testicular spermatozoa in 22 cycles. The fertilization rate was 76% for fresh semen and 87% for frozen semen. The fertilization rate was 88% for epididymal spermatozoa and 68% for testicular spermatozoa. 13 pregnancies were obtained (18.3%), 11 babies were born at term including 3 twin pregnancies. No significant difference was observed between fresh and frozen semen, or between obstructive and non-obstructive azoospermia. CONCLUSION: IVF-ICSI applied to sterility due to male infertility has revolutionized the management of sterile couples. However, as for any new procedure in medicine, we must be vigilant, as a sufficient follow-up is necessary to definitively evaluate the safety of ICSI, especially in terms of the risk of genetic abnormalities.