[Male age in assisted reproductive technologies: Is there a limit?] / Âge du père en assistance médicale à la procréation : faut-il une limite ?

In France, there does exist any age limit for infertile men management neither in the law nor for the coverage by the "French Assurance Maladie". French law specifies only that both partners of the couple have to be "of childbearing age", but there is no definition for men of childbearing age. Does legislation have to determine a limit on man management in function of his age? Could ART practitioners decide (themselves) whether they take care of infertile men or not? Should male age be a criteria to decide this management? Would ART practitioners "need" a legislation to help them to decide? In 2016, the "French Assurance Maladie" covers all costs for infertile couple if woman is less than 43 years old, whatever male age. If an age-threshold should be establish for the coverage of infertile men management by the "French Assurance Maladie", then what should be this threshold? In order to try to answer these questions, we asked them to French ART practitioners (gynecologists and embryologists) and gynecologists. The first questionnaire included 13 questions and was filled by 244 ART specialists; the second was filled by 138 gynecologists. Most of them agree to limit the male management and the coverage by the "French Assurance Maladie" at 60 for men in ART. Gynecologists who does not practice ART wish a limit for insurance (80% of them but are only 57% to wish a legal limit).

[Infertility over forty: Pros and cons of IVF]. / Prendre en charge les femmes de 40ans et plus en FIV : pour ou contre ou pour et contre ?

The population attempting pregnancy and having babies is ageing. The declining fertility potential and the late age of motherhood are increasing significantly the number of patients over forty consulting infertility specialists. Assisted reproductive technologies (ART) cannot compensate the natural decline in fertility with age. In France, in public hospital, ART is free of charge for women until 43 years, over 43, social insurance does not reimburse ART. Hence, 43 years is the usual limit, but between 40 and 42 is ART useful? The answer varies according to physicians, couples or society. On medical level, the etiology of the infertility must be taken into account. If there is an explanation to infertility (male or tubal infertility) ART is better than abstention. If the infertility is only due to age the question is raised. In France, the reimbursement by the society of a technique with very low results is discussed. However efficacy is not absolutely compulsory in Medicine. On the opposite to give false hopes may be discussed too. To obtain a reasonable consensus is rather difficult.

[Social egg freezing: which problems?]. / Conservation ovocytaire, quelle problématique ?

In today's society, many women push pregnancy further away from the "right" childbearing age. Assisted reproduction, except egg donation, is unable to fully overcome the effect of age on fertility loss. The effectiveness of oocyte vitrification is demonstrated, and oocyte vitrification is allowed in the French Bioethics law of 2011. In the French law, oocyte' s cryopreservation is proposed to oocyte donors without child. Social egg freezing for non-medical reason is already legal in some countries, but leads to new debates and discussions.

Is intracytoplasmic morphologically selected sperm injection (IMSI) beneficial in the first ART cycle? a multicentric randomized controlled trial.

Intracytoplasmic morphologically selected sperm injection (IMSI), by selecting spermatozoa at high magnification improves the outcome of intracytoplasmic sperm injection (ICSI) mainly after several failures. However, only few monocentric randomized studies are available and they do not analyse results as a function of sperm characteristics. In 255 couples attempting their first assisted reproductive technology (ART) attempt for male infertility (motile sperm count <1×106 after sperm selection, but at least 3×106 spermatozoa per ejaculate to allow a detailed analysis of sperm characteristics), a prospective randomized trial was performed to compare the clinical outcomes of IMSI and ICSI and to evaluate the influence of sperm characteristics on these outcomes. IMSI did not provide any significant improvement in the clinical outcomes compared with ICSI neither for implantation (24% vs. 23%), nor clinical pregnancy (31% vs. 33%) nor live birth rates (27% vs. 30%). Moreover, the results of IMSI were similar to the ICSI ones whatever the degree of sperm DNA fragmentation, nuclear immaturity and sperm morphology. These results show that IMSI instead of ICSI has no advantage in the first ART attempts. However, this does not rule out IMSI completely and more randomized trials must be performed especially regarding patients carrying severe teratozoospermia, or high sperm DNA fragmentation levels or having previous ICSI failures.

[Endometrial preparation in oocyte recipients]. / Préparation endométriale chez les receveuses dans un programme de don d'ovocytes.

Oocyte donation is offered to patients with premature ovarian failure to achieve pregnancy when no other assisted reproductive technology is possible. Some clinical and biological factors have been identified for influencing the outcome of oocyte donation cycles. Embryo implantation depends on embryo quality, method for the embryo transfer, and endometrial differentiation. In our center, the oocyte recipients receive for the endometrial preparatory cycle the same treatment that for the patients undergoing frozen embryos transfers, with good clinical pregnancy rates, about 35% per transfer. Estrogen and progesterone supplementation with GnRH agonist down regulation are used in synchronized protocols or for frozen embryos transfers. The synchronization between recipient's endometrium and donor's ovarian stimulation is very restrictive. Nowadays, the oocytes vitrification lithens the oocyte donation process: the endometrial preparation has a limited duration and is well controlled, and embryos that are transferred are all fresh embryos.

[Is it possible to avoid working on weekends in an Assisted Reproductive Technology program?]. / Peut-on éviter le travail du week-end en Assistance Médicale à la Procréation ?

Is it possible to safely avoid weekend oocyte retrievals and embryo transfers? It is possible to safely avoid Sunday oocyte retrieval and embryo transfers during GnRH agonist or antagonist cycles, to avoid oocyte retrievals 2 days seem also possible by delaying or advancing hCG administration in both analogs cycles but it is more difficult to avoid embryo transfers during two days. In intra uterine insemination programs, it is possible to avoid ovulation monitoring and inseminations by the use of GnRH antagonists. In IVF programs, ovulation monitoring could be avoid on weekends but the risk of ovarian hyperstimulation would exists in case of polycystic ovary or polycystic like ovary.

[Low circulating anti-Müllerian hormone and normal follicle stimulating hormone levels: which prognosis in an IVF program?]. / Pronostic en fécondation in vitro des patientes ayant une AMH basse et une FSH normale.

OBJECTIVE: To evaluate the results of controlled ovarian hyperstimulation (COH) for IVF in patients with low anti-Müllerian hormone (AMH) and normal basal follicle stimulating hormone (FSH) and Estradiol levels (≤50 pg/mL). PATIENTS AND METHODS: A retrospective cohort study including 704 patients for whom AMH and FSH levels (measured between days 3 and 5 of the menstrual cycle) were available, is performed in the IVF center at the Sèvres Hospital (France). Three groups are designed and analyzed: group 1 with AMH less or equal to 2 ng/mL and FSH less or equal to 10 mUI/mL (study group), Group 2 with AMH greater than 2 ng/mL and FSH less or equal to 10 mUI/mL (control group) and Group 3 with AMH less or equal to 2 ng/mL and FSH greater than 10 mUI/mL (group with decreased ovarian reserve). RESULTS: IVF outcome for patients from the study group is significantly worse than that of the second but not than that of the third group. In the first group, the number of retrieved oocytes, the number of total obtained embryos, the clinical pregnancy rate and the live birth rate are significantly lower than in the second group; moreover, there are more cancelled cycles because of poor response in the first group. There is no difference with the third group. DISCUSSION AND CONCLUSIONS: This study shows that women with a low baseline AMH have a similar response to COH to the poor responders patients with a decreased ovarian reserve revealed by an elevated FSH level. Thus, when a woman undergoing IVF cycle presents a low AMH, she might be considered as a poor responder patient regardless of the FSH level and, although the clinical pregnancy rate is not so disappointing (18%), the couple should be informed of a higher risk of cycle cancellation.

[In Vitro Fertilization: beware of oocyte retrieval without oocyte!]. / Fécondation in vitro : ponction blanche : méfions-nous !

A 30-year-old woman undergoing an In Vitro Fertilization (IVF) treatment for tubal infertility and for whom no oocyte was retrieved at the puncture ("white puncture") presented an ectopic pregnancy. The patient was asymptomatic except some bleeding events reported for several days prior to the puncture. The ovulation monitoring was normal throughout the stimulation by gonadotrophin and hCG was administered for the final oocyte maturation on the twelfth day of stimulation at a rate of 2771 pg/ml of estradiol with a perfect ultrasound follicular growth. This case demonstrates that we have to beware of a "white puncture" and that the hCG measurement the day of the oocyte retrieval is necessary because of the possibility of an ectopic pregnancy.

[Single embryo transfer: is Scandinavian model valuable in France?]. / Faut-il systématiser le transfert de l'embryon unique ? Le modèle scandinave est-il applicable en France ?

The aim of infertility treatment is clearly to obtain one healthy baby. If the transfer of a top quality single embryo could provide a baby to all the patients, there would be no more discussion. The problem is that, nowadays, French pregnancy rates after fresh embryo or frozen embryo transfer are not the same as in Nordic countries. All studies show that in unselected patients, single embryo transfer decreases twin pregnancy rate but decreases pregnancy rate too. Pregnancy rate is dependent on embryo quality, women's age, rank of IVF attempt (clear data) but also on body mass index, ovarian reserve, smoking habits. All these data cannot be taken into account in a law. That is the reason why a flexible policy of transfer adapted to each couple is preferable. Each couple and each IVF team are unique and must keep the freedom to choose how many embryos must be transferred to obtain healthy babies, and to avoid twin pregnancies but without demonizing them.

[Intra-uterine insemination: ovarian stimulation or not?]. / Insémination intra-utérine: pourquoi continuer à stimuler l'ovulation?

Conflicting results have been published about intra-uterine insemination efficacy. In many studies, success rates is due to ovarian stimulation and number of follicles. In the present fight against multiple pregnancies, ovarian stimulation is discussed and present pregnancy rates are weak. Our aim is to demonstrate that there is a place for the association controlled ovarian hyperstimulation and intra-uterine insemination in the field of infertility treatments. It is possible to try and recognise women at high risk of multiple pregnancies, keeping the benefit of ovarian stimulation.

Cyclic FEE peptide increases human gamete fusion and potentiates its RGD-induced inhibition.

BACKGROUND: Alpha6beta1 integrin has been proposed to act as a sperm receptor on the mouse oocyte by interacting with spermatozoon fertilin beta. We investigated, in humans, whether oocyte integrins could act similarly in gamete fusion, using a cyclic peptide containing the putative disintegrin-binding domain of human fertilin beta [cyclic FEE (cFEE)] and RGD peptide. METHODS: Zona-free eggs were inseminated in the absence or presence of peptides. To maintain the membrane protein pattern, the zona pellucida was removed by microdissection. Immunofluorescence and confocal microscopy were used to detect integrin subunits on the oocyte. RESULTS: Unexpectedly, cFEE alone increased human gamete fusion by 94% instead of inhibiting fertilization. Furthermore, cFEE together with RGD potentiated the RGD-induced inhibition of fertilization in a dose-dependent manner. The data suggested the hypothesis of integrin cross-talk, further supported by the co-localization of alpha6beta1 and alphavbeta3 integrins, the putative receptors of cFEE and RGD peptides, respectively. CONCLUSIONS: RGD-sensitive and -insensitive integrins may be associated in a multimolecular complex working as a sperm receptor on the human oocyte membrane. Supplementation of human IVF culture medium with cFEE peptide might improve fertilization rates in ART.

[Leucocytospermia, oxidative stress and male fertility: facts and hypotheses]. / Leucospermie, stress oxydatif et fertilité masculine: certitudes et hypothèses.

Leukocytospermia is frequent and significantly increased (over 10(6)/ml) in 20% of male factor infertility. It induces the production of highly toxic reactive oxygen species (ROS) which impair genital track accessory glands and sperm cell functions. The seminal medium contains extremely potent antioxidative defenses which usually balance the oxidative stress. In vivo, these defenses can be overwhelmed when ROS production is extremely important and/or when it lasts for a very long period of time. Infertility can then appear. In vitro, ROS have been univoqually demonstrated for being highly toxic since spermatozoa are no longer protected. Sperm cell defects are : decrease of acrosome reaction and fusiogenic ability and increase of DNA fragmentations. In case of male factor infertility, a leukocytospermia represents an essential or an additional risk factor that should be treated, specially when in vitro therapy is to be scheduled, in order to improve gamete quality.