Diagnosis and treatment of male infertility-related fertilization failure

Infertility affects approximately 15% of reproductive-aged couples worldwide, of which up to 30% of the cases are caused by male factors alone. The origin of male infertility is mostly attributed to sperm abnormalities, of which many are caused by genetic defects. The development of intracytoplasmic sperm injection (ICSI) has helped to circumvent most male infertility conditions. However, there is still a challenging group of infertile males whose sperm, although having normal sperm parameters, are unable to activate the oocyte, even after ICSI treatment. While ICSI generally allows fertilization rates of 70 to 80%, total fertilization failure (FF) still occurs in 1 to 3% of ICSI cycles. Phospholipase C zeta (PLC zeta) has been demonstrated to be a critical sperm oocyte activating factor (SOAF) and the absence, reduced, or altered forms of PLC zeta have been shown to cause male infertility-related FF. The purpose of this review is to (i) summarize the current knowledge on PLC zeta as the critical sperm factor for successful fertilization, as well as to discuss the existence of alternative sperm-induced oocyte activation mechanisms, (ii) describe the diagnostic tests available to determine the cause of FF, and (iii) summarize the beneficial effect of assisted oocyte activation (AOA) to overcome FF

Multivariate analysis identifies the estradiol level at ovulation triggering as an independent predictor of the first trimester pregnancy-associated plasma protein-A level in IVF/ICSI pregnancies

STUDY QUESTION: Can independent predictors of pregnancy-associated plasma protein-A (PAPP-A) levels be identified in a group of women who conceived following IVF/ICSI? SUMMARY ANSWER: The significantly decreased PAPP-A level in IVF and ICSI pregnancies compared with non-IVF/ICSI pregnancies was correlated strongly with the serum estradiol (E2) level at ovulation triggering. WHAT IS KNOWN ALREADY: The first trimester prenatal combined screening test for fetal aneuploidies in pregnancies conceived following assisted reproduction techniques (ART) is complicated by an alteration of the maternal biomarkers free β-hCG and PAPP-A, causing a higher false-positive rate compared with pregnancies which are conceived naturally. The use of controlled ovarian stimulation prior to IVF/ICSI is suggested to be the principle reason for these alterations of biomarkers in ART pregnancies. STUDY DESIGN, SIZE, DURATION: Between January 2010 and December 2011, 1474 women who conceived naturally and 374 women who conceived following IVF (n = 89), ICSI (n = 204) or intrauterine insemination (IUI, n = 81) were included in this retrospective study. Only singleton pregnancies were eligible for this study. For all women, serum analysis was performed in the same clinical laboratory. Measurement of nuchal translucency (NT) thickness was performed by four physicians belonging to the same infertility centre. PARTICIPANTS/MATERIALS, SETTING, METHODS: First-trimester combined screening test of aneuploidy parameters (maternal age, PAPP-A and free β-hCG, NT thickness) were compared between non-ART and ART (IVF, ICSI and IUI) singleton pregnancies. Next, a minimal threshold E2 level at ovulation triggering was suggested for IVF/ICSI pregnancies above which the PAPP-A levels were significantly decreased compared with non-ART pregnancies. Finally, a multivariate analysis was performed to reveal independent predictors of PAPP-A level in IVF/ICSI pregnancies. MAIN RESULTS AND THE ROLE OF CHANCE: We showed a decrease of the multiple of the median (MoM) PAPP-A level in IVF and ICSI singleton pregnancies compared with non-ART singleton pregnancies (P < 0.001), with MoM values of 0.74 (0.16-3.16) and 0.81 (0.12-4.61) versus 0.98 (0.14-5.76), respectively. Analysis of variance of the overall model was highly significant (Fisher test 3.76, P = 0.01), indicating that the model explains a significant portion of the variation in the data. No difference in PAPP-A level was found between non-ART and IUI pregnancies. The free β-hCG level and NT thickness did not differ between ART and non-ART pregnancies. PAPP-A levels in IVF and ICSI pregnancies were strongly correlated with the E2 level at ovulation triggering. We showed by multivariate analysis that an E2 cut-off level of 1300 pg/ml at the time of ovulation could predict a significantly lower PAPP-A level at first trimester combined screening (β -0.239 ± 0.088, P < 0.005). LIMITATION, REASONS FOR CAUTION: The measures of biochemical markers can differ between laboratories and with the used equipment; therefore, extrapolation of the E2 cut-off level to other infertility centres should be undertaken with caution. WIDER IMPLICATIONS OF THE FINDINGS: One should be careful when using correction factors for ART patients undergoing the first trimester combined screening test. The proposed E2 cut-off level may help to identify a subgroup of women within the population of ART patients for whom use of a correction factor is justified. STUDY FUNDING/COMPETING INTEREST(S): None

Anonieme donatie van gameten: de maatstaf?

Het aantal patiënten dat de laatste jaren een beroep doet op geassisteerde voortplantingstechnieken stijgt. Ook de vraag naar donorgameten groeit. In België is momenteel bij wet de anonimiteit van de donor de regel. Niet-anonieme donatie is enkel toegestaan indien zowel de donor als de ontvanger hierin toestemmen. Dit is niet overal in de wereld het geval en anonimiteit bij donatie van gameten wordt niet langer als vanzelfsprekend beschouwd. Enkele vooraanstaande ethische commissies sluiten de mogelijkheid van contact tussen donoren en nakomelingen niet langer uit en openden het debat hieromtrent. Dit artikel geeft een overzicht van de argumenten voor en tegen de anonieme donatie van gameten. In de literatuur is nagegaan of onderzoek hieromtrent reeds werd verricht. Tot slot wordt gesteld dat, in het belang van alle betrokken partijen, een sfeer van openheid moet kunnen gecreëerd worden, waarbinnen ieder voor zichzelf een geïnformeerde en gegronde keuze kan maken tot welke informatie hij/zij toegang wenst voor zichzelf en/of voor zijn/haar nakomelingen en familie