A large observational data study supporting the PROsPeR score classification in poor ovarian responders according to live birth outcome.

STUDY QUESTION: Can the Poor Responder Outcome Prediction (PROsPeR) score identify live birth outcomes in subpopulations of patients with poor ovarian response (POR) defined according to the ESHRE Bologna criteria (female age, anti-Müllerian hormone (AMH), number of oocytes retrieved during the previous cycle (PNO) after treatment with originator recombinant human follitropin alfa? SUMMARY ANSWER: The PROsPeR score discriminated the probability of live birth in patients with POR using observational data with fair discrimination (AUC ≅ 70%) and calibration, and the AUC losing less than 5% precision compared with a model developed using the observational data. WHAT IS KNOWN ALREADY: Although scoring systems for the likelihood of live birth after ART have been developed, their accuracy may be insufficient, as they have generally been developed in the general population with infertility and were not validated for patients with POR. The PROsPeR score was developed using data from the follitropin alfa (GONAL-f; Merck KGaA, Darmstadt, Germany) arm of the Efficacy and Safety of Pergoveris in Assisted Reproductive Technology (ESPART) randomized controlled trial (RCT) and classifies women with POR as mild, moderate or severe, based upon three variables: female age, serum AMH level and number of oocytes retrieved during the previous cycle (PNO). STUDY DESIGN, SIZE, DURATION: The external validation of the PROsPeR score was completed using data derived from eight different centres in France. In addition, the follitropin alfa data from the ESPART RCT, originally used to develop the PROsPeR score, were used as reference cohort. The external validation of the PROsPeR score l was assessed using AUC. A predetermined non-inferiority limit of 0.10 compared with a reference sample and calibration (Hosmer-Lemeshow test) were the two conditions required for evaluation. PARTICIPANTS/MATERIALS, SETTING, METHODS: The observational cohort included data from 8085 ART treatment cycles performed with follitropin alfa in patients with POR defined according to the ESHRE Bologna criteria (17.6% of the initial data set). The ESPART cohort included 477 ART treatment cycles with ovarian stimulation performed with follitropin alfa in patients with POR. MAIN RESULTS AND THE ROLE OF CHANCE: The external validation of the PROsPeR score to identify subpopulations of women with POR with different live birth outcomes was shown in the observational cohort (AUC = 0.688; 95% CI: 0.662, 0.714) compared with the ESPART cohort (AUC = 0.695; 95% CI: 0.623, 0.767). The AUC difference was -0.0074 (95% CI: -0.083, 0.0689). This provided evidence, with 97.5% one-sided confidence, that there was a maximum estimated loss of 8.4% in discrimination between the observational cohort and the ESPART cohort, which was below the predetermined margin of 10%. The Hosmer-Lemeshow test did not reject the calibration when comparing observed and predicted data (Hosmer-Lemeshow test = 1.266688; P = 0.260). LIMITATIONS, REASONS FOR CAUTION: The study was based on secondary use of data that had not been collected specifically for the analysis reported here and the number of characteristics used to classify women with POR was limited to the available data. The data were from a limited number of ART centres in a single country, which may present a bias risk; however, baseline patient data were similar to other POR studies. WIDER IMPLICATIONS OF THE FINDINGS: This evaluation of the PROsPeR score using observational data supports the notion that the likelihood of live birth may be calculated with reasonable precision using three readily available pieces of data (female age, serum AMH and PNO). The PROsPeR score has potential to be used to discriminate expected probability of live birth according to the degree of POR (mild, moderate, severe) after treatment with follitropin alfa, enabling comparison of performance at one centre over time and the comparison between centres. STUDY FUNDING/COMPETING INTEREST(S): This analysis was funded by Merck KGaA, Darmstadt, Germany. P.L. received grants from Merck KGaA, outside of the submitted work. N.M. reports grants, personal fees and non-financial support from Merck KGaA outside the submitted work. T.D.H. is Vice President and Head of Global Medical Affairs Fertility, Research and Development at Merck KGaA, Darmstadt, Germany. P.A. has received personal fees from Merck KGaA, Darmstadt, Germany, outside the submitted work. C.R. has received grants and personal fees from Gedeon Richter and Merck Serono S.A.S., France, an affiliate of Merck KGaA, Darmstadt, Germany, outside the submitted work. P.S. reports congress support from Merck Serono S.A.S., France (an affiliate of Merck KGaA, Darmstadt, Germany), Gedeon Richter, TEVA and MDS outside the submitted work. C.A., J.P., G.P. and R.W. declare no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

IVF outcomes in patients with a history of bariatric surgery: a multicenter retrospective cohort study.

STUDY QUESTION: How does a history of dramatic weight loss linked to bariatric surgery impact IVF outcomes? SUMMARY ANSWER: Women with a history of bariatric surgery who had undergone IVF had a comparable cumulative live birth rate (CLBR) to non-operated patients of the same BMI after the first IVF cycle. WHAT IS KNOWN ALREADY: In the current context of increasing prevalence of obesity in women of reproductive age, weight loss induced by bariatric surgery has been shown to improve spontaneous fertility in obese women. However, little is known on the clinical benefit of bariatric surgery in obese infertile women undergoing IVF. STUDY DESIGN, SIZE, DURATION: This exploratory retrospective multicenter cohort study was conducted in 10 287 IVF/ICSI cycles performed between 2012 and 2016. We compared the outcome of the first IVF cycle in women with a history of bariatric surgery to two age-matched groups composed of non-operated women matched on the post-operative BMI of cases, and non-operated severely obese women. PARTICIPANTS/MATERIALS, SETTING, METHODS: The three exposure groups of age-matched women undergoing their first IVF cycle were compared: Group 1: 83 women with a history of bariatric surgery (exposure, mean BMI 28.9 kg/m2); Group 2: 166 non-operated women (non-exposed to bariatric surgery, mean BMI = 28.8 kg/m2) with a similar BMI to Group 1 at the time of IVF treatment; and Group 3: 83 non-operated severely obese women (non-exposed to bariatric surgery, mean BMI = 37.7 kg/m2). The main outcome measure was the CLBR. Secondary outcomes were the number of mature oocytes retrieved and embryos obtained, implantation and miscarriage rates, live birth rate per transfer as well as birthweight. MAIN RESULTS AND THE ROLE OF CHANCE: No significant difference in CLBR between the operated Group 1 patients and the two non-operated Groups 2 and 3 was observed (22.9%, 25.9%, and 12.0%, in Groups 1, 2 and 3, respectively). No significant difference in average number of mature oocytes and embryos obtained was observed among the three groups. The implantation rates were not different between Groups 1 and 2 (13.8% versus 13.7%), and although lower (6.9%) in obese women of Group 3, this difference was not statistically significant. Miscarriage rates in Groups 1, 2 and 3 were 38.7%, 35.8% and 56.5%, respectively (P = 0.256). Live birth rate per transfer in obese patients was significantly lower compared to the other two groups (20%, 18%, 9.3%, respectively, in Groups 1, 2 and 3, P = 0.0167). Multivariate analysis revealed that a 1-unit lower BMI increased the chances of live birth by 9%. In operated women, a significantly smaller weight for gestational age was observed in newborns of Group 1 compared to Group 3 (P = 0.04). LIMITATIONS, REASONS FOR CAUTION: This study was conducted in France and nearly all patients were Caucasian, questioning the generalizability of the results in other countries and ethnicities. Moreover, 950 women per group would be needed to achieve a properly powered study in order to detect a significant improvement in live birth rate after bariatric surgery as compared to infertile obese women. WIDER IMPLICATIONS OF THE FINDINGS: These data fuel the debate on the importance of pluridisciplinary care of infertile obese women, and advocate for further discussion on whether bariatric surgery should be proposed in severely obese infertile women before IVF. However, in light of the present results, infertile women with a history of bariatric surgery can be reassured that surgery-induced dramatic weight loss has no significant impact on IVF prognosis. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by unrestricted grants from FINOX-Gédéon Richter and FERRING Pharmaceuticals awarded to the ART center of the Clinique Mathilde to fund the data collection and the statistical analysis. There are no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: NCT02884258.

Disparities in reproductive outcomes according to the endometrial preparation protocol in frozen embryo transfer : The risk of early pregnancy loss in frozen embryo transfer cycles.

PURPOSE: The purpose of this study was to determine the effect of stimulated and artificial endometrial preparation protocols on reproductive outcomes in frozen embryo transfer (FET) cycles. METHODS: We performed a retrospective study of 1926 FET cycles over a 3.5-year period in the Fertility Unit at a University Hospital. Stimulated and artificial protocols were used for endometrial preparation. The embryos for FET were obtained from either in vitro fertilization or intracytoplasmic sperm injection cycles. Live birth rate and early pregnancy loss rates were retrospectively compared. In artificial protocols, oral or vaginal administration of oestradiol 2 mg two or three times a day was followed by vaginal supplementation with progesterone 200 mg two or three times a day. In stimulated protocols, recombinant follicle-stimulating hormone was administered from day 4 onward. Vaginal ultrasound was used for endometrial and ovarian monitoring. A pregnancy test was performed 14 days after FET. If it was positive, oestradiol and progesterone were administered up until the 12th week of gestation in artificial cycles. We defined early pregnancy losses as biochemical pregnancies (preclinical losses) and miscarriages. RESULTS: Data on 865 artificial cycles (45% of the total) and 1061 stimulated cycles (55%) were collected. Early pregnancy loss rate was significantly lower for stimulated cycles (34.2%) than for artificial cycles (56.9%), and the live birth rate was significantly higher for stimulated cycles (59.7%) than for artificial cycles (29.1%). CONCLUSION: In frozen embryo transfer, artificial cycles were associated with more early pregnancy loss and lower live birth rate than stimulated cycles.

High-magnification selection of spermatozoa prior to oocyte injection: confirmed and potential indications.

Intracytoplasmic morphologically selected sperm injection (IMSI) involves the use of differential interference contrast microscopy at high magnification (at least ·6300) to improve the observation of live human spermatozoa (particularly by showing sperm head vacuoles that are not necessarily seen at lower magnifications) prior to intracytoplasmic sperm injection (ICSI) into the oocyte. However, a decade after IMSI's introduction, the technique's indications and ability to increase pregnancy and/or birth rates (relative to conventional ICSI) are subject to debate. In an attempt to clarify this debate, this work performed a systematic literature review according to the PRISMA guidelines. The PubMed database was searched from 2001 onwards with the terms 'IMSI', 'MSOME' and 'high-magnification, sperm'. Out of 168 search results, 22 relevant studies reporting IMSI outcomes in terms of blastocyst, pregnancy, delivery and/or birth rates were selected and reviewed. The studies' methodologies and results are described and discussed herein. In view of the scarcity of head-to-head IMSI versus ICSI studies, the only confirmed indication for IMSI is recurrent implantation failure following ICSI. All other potential indications of IMSI require further investigation.

A genome-wide DNA methylation study in azoospermia.

The objective of this study was to assess genome-wide DNA methylation in testicular tissue from azoospermic patients. A total of 94 azoospermic patients were recruited and classified into three groups: 29 patients presented obstructive azoospermia (OA), 26 displayed non-obstructive azoospermia (NOA) and successful retrieval of spermatozoa by testicular sperm extraction (TESE+) and 39 displayed NOA and failure to retrieve spermatozoa by TESE (TESE-). An Illumina Infinium Human Methylation27 BeadChip DNA methylation array was used to establish a testicular DNA methylation pattern for each type of azoospermic patient. The OA and NOA groups were compared in terms of the relative M-value (the log2 ratio between methylated and non-methylated probe intensities) for each CpG site. We observed significantly different DNA methylation profiles for the NOA and OA groups, with differences at over 9000 of the 27 578 CpG sites; 212 CpG sites had a relative M-value >3. The results highlighted 14 testis-specific genes. Patient clustering with respect to these 212 CpG sites corresponded closely to the clinical classification. The DNA methylation patterns showed that in the NOA group, 78 of the 212 CpG sites were hypomethylated and 134 were hypermethylated (relative to the OA group). On the basis of these DNA methylation profiles, azoospermic patients could be classified as OA or NOA by considering the 212 CpG sites with the greatest methylation differences. Furthermore, we identified genes that may provide insight into the mechanism of idiopathic NOA.

Tumor necrosis factor-308 polymorphism increases the embryo implantation rate in women undergoing in vitro fertilization.

STUDY QUESTION: Do TNF-308 and -238 polymorphisms impact the embryo implantation rate after in vitro fertilization (IVF) in women without female infertility factor? SUMMARY ANSWER: The presence of the TNF-308A allele is associated with high implantation and multiple pregnancy rates in women without known infertility factors after ovarian hyperstimulation with exogenous FSH. WHAT IS ALREADY KNOWN: Multiple pregnancies are frequent after the use of Assisted Reproductive Technologies. Single embryo transfer (SET) has been proposed as a simple way to prevent these risks. However, the extension of SET indications to patients not selected based on specific criteria is controversial because of reduced pregnancy rates. To date, the predictive value of the parameters used for SET (age, gynecological history of the patient and uterine characteristics) allows a pregnancy rate of ~30%. STUDY DESIGN, SIZE, DURATION: The potential predictive value of TNF polymorphisms (-308, rs1800629 and -238, rs361525) on implantation rate was evaluated in 424 women requiring IVF due to male fertility factors. This cohort retrospective study was conducted over 4 years in University-affiliated hospitals. PARTICIPANTS, SETTING, METHODS: The entire patient group included 424 women undergoing intracytoplasmic sperm injection (ICSI) due to male fertility factors without the contribution of any female factor. From among this group, a selected patient group included 120 women with a normal karyotype, age under 38 years, serum follicle-stimulating hormone (Day-3 FSH) levels below 10 IU/l, a long agonist desensitization protocol associated with recombinant FSH treatment and a Caucasian background. MAIN RESULTS AND THE ROLE OF CHANCE: The TNF-238 polymorphism was not associated with implantation rate. In contrast, the presence of the TNF-308A allele was associated with increased Day 3-E2 levels as well as higher implantation and multiple pregnancy rates after fresh embryo transfer in women from the entire and selected patient groups. Moreover, in the selected patient group, the presence of the TNF-308A allele was also associated with a decrease in the miscarriage rate. The benefit of the TNF-308A allele in predicting implantation rates was not observed after the use of frozen embryos. LIMITATIONS, REASONS FOR CAUTION: Future studies are needed to evaluate whether the TNF-308A allele might also be a biomarker in women with infertility factors. WIDER IMPLICATIONS OF THE FINDING: The TNF-308A allele may represent a good candidate for a potential predictive, non-invasive biomarker in the SET strategy. However, its impact should be evaluated in prospective studies. STUDY FUNDING/COMPETING INTEREST: This study was conducted with financial support from the French Institute for Health and Medical Research (INSERM), Organon France for a FARO (Fond d'Aide à la Recherche Organon) fellowship (to V.T.) and CHU Nice PHRC (PHRC 09-279).There are no competing interests.

Small human sperm vacuoles observed under high magnification are pocket-like nuclear concavities linked to chromatin condensation failure.

Since an embryo's ability to grow to the blastocyst stage and implant can be improved by selection of a normal spermatozoon with a vacuole-free head, this study set out to determine the nature of small sperm vacuoles observed under high magnification (>×6300). For 15 infertile men with various sperm profiles, high-magnification microscopy was used to select motile, morphometrically normal spermatozoa with no vacuoles (n=450) or more than two small vacuoles (each of which occupied less than 4% of the head's area; n=450). Spermatozoa acrosome reaction status and degree of chromatin condensation were analysed. Three-dimensional deconvolution microscopy was used to accurately image the nucleus and acrosome at all depths in all spermatozoa. In all 450 spermatozoa with small vacuoles, the latter were seen to be abnormal, DNA-free nuclear concavities. Spermatozoa with small vacuoles were significantly more likely than vacuole-free spermatozoa to have noncondensed chromatin (39.8% versus 9.3%, respectively; P<0.0001). There was no significant difference between the two groups of spermatozoa in terms of acrosome reaction status. No association between chromatin condensation and acrosome reaction status was observed. Small human sperm vacuoles observed under high magnification are pocket-like nuclear concavities related to failure of chromatin condensation.

[Sexuality and infertility]. / Sexualité et infertilité

Following the recent medical innovations, it is now possible to disassociate sexuality and reproduction. With contraception, people can have free sexuality without the fear of an unexpected pregnancy. Frequently, Assisted Reproductive Technologies (ART), with in vitro fertilization, can obtain a pregnancy without intercourse. There are three major problems concerning infertility and sexuality. Firstly, infertility because of a sexual disorder; secondly, sexual disorder induced by infertility diagnosis; thirdly, sexual disorder induced by ART. Praticians should be aware of possible existence of sexual problems to allow the couple to express them. Once diagnosed, these troubles can be treated by the pratician himself or the couple has to be referred to a psychologist or a sexologist.

Follicular fluid protein content (FSH, LH, PG4, E2 and AMH) and polar body aneuploidy.

PURPOSE: Our objective was to identify a marker for oocyte aneuploidy in follicular fluid (FF) in women with an increased risk of oocyte aneuploidy after controlled ovarian hyperstimulation. MATERIALS AND METHODS: Three groups of oocytes were constituted for polar body screening by FISH (chromosomes 13, 16, 18, 21 and 22): Group 1, advanced maternal age (n = 156); Group 2, implantation failure (i.e. no pregnancy after the transfer of more than 10 embryos; n = 101) and Group 3, implantation failure and advanced maternal age (n = 56). FSH and other proteins were assayed in the corresponding FF samples. RESULTS: Of the 313 oocytes assessed, 35.78 % were abnormal. We found a significant difference between the follicular FSH levels in normal oocytes and abnormal oocytes (4.85 ± 1.75 IU/L vs. 5.41 ± 2.47 IU/L, respectively; p = 0.021). We found that the greater the number of chromosomal abnormalities per oocyte (between 0 and 3), the higher the follicular FSH level. CONCLUSION: High FF FSH levels were associated with oocyte aneuploidy in women having undergone controlled ovarian hyperstimulation.

[Intra-uterine insemination outcomes according to the serum AMH level on day 3]. / Valeur prédictive de l'hormone antimüllérienne sur les issues des inséminations intra-utérines.

UNLABELLED: The aim of this retrospective study was to compare the IUI outcomes according to serum antiMullerian hormone (AMH) levels on day 3 of cycle. PATIENTS AND METHOD: Three hundred and sixteen patients undergoing their first IUI cycle after a serum AMH level test in our laboratory. These patients were less than 39 years of age and the number of motile spermatozoa inseminated (NMSI) was superior or equal to five millions. Patients were divided in three groups according to their serum AMH level: the group 1 with AMH level less than 1ng/ml, the group 2 with AMH level between 1 and 4.5ng/ml, and the group 3 with AMH level greater than 4.5ng/ml. MAIN OUTCOMES MEASURE(S): clinical pregnancy rate and ongoing pregnancy rate per IUI cycle. RESULT(S): No statistical difference has been observed on follicle stimulation, number of mature follicle, oestradiol level on day hCG, clinical pregnancy rate, spontaneous abortion. The ongoing pregnancy rate per IUI practised were respectively: 15.5% for AMH inferior to 1ng/ml versus 15.2% for AMH between 1 to 4.5ng/ml and versus 13.6% for AMH superior to 4.5ng/ml. CONCLUSION(S): AMH value does not seem to have an impact on the IUI outcomes and particularly on the pregnancy rates.

[The experiences of patients and the maternal representations throughout the different steps of an oocyte donation]. / Le vécu des patientes et les représentations maternelles au fil des étapes d'un don d'ovocytes.

This research aims to study the experiences and the maternal representations of infertile women throughout the different steps of a medically assisted procreation (MAP) with oocyte donation. The analysis of collected data (interviews and questionnaires) shows that the resort of egg donation creates psychic adjustment (particularly in terms of maternal representations) that appear specific to this type of procreation.

[Ovarian stimulation monitoring: past, present and perspectives]. / Le monitorage de l'ovulation : passé, présent et perspectives.

Since the inception of Assisted Reproductive Technology (ART), knowing the moment of ovulation has always been a priority. Initially, the monitoring was accomplished by observing the luteinizing hormone (LH) surge just before ovulation. Currently, in all ART facilities, the monitoring of all stimulated ovulatory cycles is done by using the conventional two-dimensional (2D) ultrasound to measure follicle diameter and by drawing blood tests that measure estradiol, progesterone, and luteinizing hormone levels. These exams allow determination of the numbers and quality of growing ovarian follicles and evaluation of follicle maturity before choosing the appropriate time for ovulation triggering. The monitoring of ovulatory cycles has now become enhanced with the arrival of new software called SonoAVC. This software allows the utilization of 3D blocks to immediately calculate the total number and volume of the follicles inside the ovary. This automatic approach is faster, precise, and more efficient. It also has better reproducibility than the classical 2D diameters. Furthermore, certain ART professionals envision that by using the SonoVac technology, patients will no longer need to be monitored with regular ultrasounds and with systematic hormonal testing.

Higher interleukin-18 and mannose-binding lectin are present in uterine lumen of patients with unexplained infertility.

The uterine luminal environment was explored with regard to interleukin-18 (IL-18) and mannose-binding lectin (MBL) and the possibility that the procedure of flushing the uterine cavity would optimize the physiological initial pseudo-inflammatory uterine reaction. Uterine flushings were performed among 175 IVF/intracytoplasmic sperm injection (ICSI) patients at the time of oocyte retrieval and the cycles were compared with a control group matched for age, number of previous attempts and type of assisted reproductive procedure (IVF or ICSI) in which no flushing were performed (n = 175). Samples collected were divided into two groups according to the presence/absence of endometrial cells in samples. IL-18 and MBL expressions were explored by enzyme-linked immunosorbent assay. Implantation rates were significantly higher in those patients who underwent the uterine flushing compared with controls (P = 0.04). Luminal concentrations of IL-18 and MBL were higher if endometrial cells were present in flushings, suggesting endometrial origin of the secretion. Both concentrations of MBL and IL-18 were higher in patients with unexplained infertility compared with patients involved in IVF/ICSI for male or tubal infertility (P = 0.005 and 0.02, respectively). The exploration of the endoluminal environment before oocyte retrieval may enhance pregnancy rates and show distinct features in patients with unexplained infertility.

Preconceptional diagnosis for Robertsonian translocation as an alternative to preimplantation genetic diagnosis in two situations: a pilot study.

INTRODUCTION: Preimplantation genetic diagnosis (PGD) is widely used for women heterozygous for a Robertsonian translocation. Preconceptional diagnosis (PCD), performed before fertilization, may be an alternative to PGD, especially in countries where PGD is restricted or prohibited, as in France. It could also give different information and clarify the influence of reproductive and obstetric history. METHODS: In our study, translocation was diagnosed before ICSI in five cases (group A), and after newborn or fetal aneuploidy or miscarriage in two cases, (group B). RESULTS: First polar body (PB1) analysis using acrocentric centromeric probes was done for 85 PB1s, and aneuploidy rate was at 42.4%. Oocyte aneuploidy rate differed (p<0.0001) between groups A and B (30% vs 84%). Despite the small group sizes, we demonstrate a correlation (p=0.0358) of aneuploidy rate in polar bodies after 2 or more attempts. Three live births were recorded, all in group A. DISCUSSION: PCD could thus be an alternative to PGD. This pilot study also provides new prognostic information taking into account the women's natural history, but further confirmation is required.

Gamete cytogenetic study in couples with implantation failure: aneuploidy rate is increased in both couple members.

PURPOSE: Implantation failure is known to be associated with an increased risk of aneuploidy in embryos, a situation leading to a pre-implantation genetic screening, not allowed in different countries like France. Our aim was to evaluate the gamete aneuploidy incidence in this context, using first polar body and spermatozoa aneuploidy screening. METHODS: Three groups were considered: 11 couples with pregnancy obtained after IVF for female infertility (group 1); 20 couples with pregnancy obtained after IVF for male infertility (group 2); and 35 couples with implantation failure (group 3). In group 3, 28 couples treated by ICSI volunteered for first polar body analysis (PB1). RESULTS: Spermatozoa aneuploidy rate was increased in groups 2 (1.6%) and 3 (2.1%) in comparison to group 1 (0.6%). PB1 aneuploidy rate was 35.4% in group 3. Finally, eight couples (32%) had no particular chromosomal risk in gametes, 15/25 (60%) presented an increased spermatic (>2%) or oocyte (>1/3) aneuploidy rate, and 2/25 (8%) had both. CONCLUSION: Those results confirm that implantation failure has a heterogeneous origin, that gamete chromosome abnormality rate is one of the major contributing factors, and that 1st Polar body and spermatozoa aneuploidy screening or pre-implantation genetics screening may be indicated for these couples.

Stability of aneuploidy rate in polar bodies in two cohorts from the same patient.

The aim of this study was to evaluate the stability of the aneuploidy rate of the first polar body. Knowing the stability of the oocyte aneuploidy rate for each patient would allow the first analysis to be used as a prognostic tool for further attempts at intracytoplasmic sperm injection (ICSI). After a first unsuccessful ICSI attempt with preconceptional screening, 24 women underwent a second attempt. First polar body aneuploidy rates were compared in the course of two successive ovarian stimulations. The first polar body was biopsied after laser dissection of the zona pellucida and five chromosomes were analysed using the MultiVysion polar body multicolour probe panel. A total of 200 polar bodies were analysed; 91 and 109 in the first and second ICSI attempts, respectively. The total aneuploidy rate was identical in the first and second attempts; 44.0% (40/91) and 44.0% (48/109), respectively. The first evaluation of the aneuploidy rate was statistically (P = 0.0007) correlated with the second, with a correlation coefficient, r = 0.707. The stability of the aneuploidy rate in different cohorts from the same patient, if confirmed in a larger series, makes this parameter a useful tool for counselling couples.

[True and false hyperprolactinemia: how to discriminate one from the other in infertility management?]. / Vraies et fausses hyperprolactinémies: comment les distinguer, dans le cadre du bilan d'infertilité?

Serum prolactin measurement is usually performed in infertility evaluation, even if there's no specific clinical presentation of hyperprolactinemia. High levels of prolactin are noted in 20 to 30% of menstrual abnormalities and in about 10% of regular menses. It is of importance to determine whether hyperprolactinemia is related to pituitary adenoma, drug administration, general diseases, or circulating large forms of prolactin, in order to avoid heavy, expensive, time consuming and unnecessary clinical investigations or therapeutic actions. We must first to confirm the biological diagnosis of hyperprolactinemia with few repeated plasmatic measurements, and, later, if necessary use TRH-metoclopramide test and/or pituitary magnetic resonance imaging.

An idiopathic infertility with oocytes metaphase I maturation block: case report.

BACKGROUND: A case of idiopathic primary infertility was attributed to a block in oocyte meiosis affecting the transition between metaphase I and metaphase II. METHODS AND RESULTS: A couple suffering unexplained primary infertility was unsuccessfully treated by various means of assisted reproductive technology. After four unsuccessful pregnancy attempts using intrauterine inseminations (IUI), IVF was attempted (all oocytes remained unfertilized), followed by an ICSI cycle. None of the retrieved oocytes expelled the polar body, and therefore were not injected. The failure of these assisted reproduction cycles was, in both cases, due to the immaturity of the oocytes recovered. Cytogenetic analysis of the oocytes retrieved for ICSI provided evidence of meiotic arrest. Using cytogenetic staging criteria we were able to show that this arrest occurred between metaphase I and anaphase I. CONCLUSIONS: Meiotic blocks affecting oocytes have already been described for various mammals. We discuss here mechanisms that might be involved in this possibly inherited disorder in humans, and ways in which our knowledge of them could be increased.

[Can donor insemination be optimised?]. / Peut-on optimiser l'insémination avec donneur?

OBJECTIVE: To compare the different donor insemination technics. MATERIAL AND METHOD: Analysis of the published studies about donor insemination which value the effectiveness of Intra Cervical Insemination (ICID) and Intra Uterine Insemination (IUID), the interest of ovulation induction, the possible complications, and the cost-effectiveness ratio. RESULTS: The meta-analysis of the Cochrane data base (10 comparative studies IUID versus ICID, 2568 donor insemination cycles) lead to a pregnancy rate per cycle (PRC) 17.77% with IUID versus 7.68% with ICID. The odds ratio is 2.63 (CI from 1.85 to 3.73). With these PRC, the direct cost per evolutive pregnancy is 54,780 F with ICID and 25,675 F with IUID. CONCLUSION: If it is possible to propose ICID to patient with an excellent regularity of ovulation. IUID with ovulation induction by gonadotropins is today the gold standard, and more especially as the law restrict the number of donor inseminations. Indeed, the IUID is two or three times more effective than ICID, consume the half of sperm straws, use a semen of moderate quality, there is no complication provided that the cycle is cancelled if there is more than two mature follicles and the cost-effectiveness ratio is greatly in favour with IUID.