Charlotte Dupont

Obesity leads to higher risk of sperm DNA damage in infertile patients

There has been a growing interest over the past few years in the impact of male nutrition on fertility. Infertility has been linked to male overweight or obesity, and conventional semen parameter values seem to be altered in case of high body mass index (BMI). A few studies assessing the impact of BMI on sperm DNA integrity have been published, but they did not lead to a strong consensus. Our objective was to explore further the relationship between sperm DNA integrity and BMI, through a 3-year multicentre study. Three hundred and thirty male partners in subfertile couples were included. Using the terminal uridine nick-end labelling (TUNEL) assay, we observed an increased rate of sperm DNA damage in obese men (odds ratio (95% confidence interval): 2.5 (1.2-5.1)).

Maternal environment and the reproductive function of the offspring

Fetal programming of metabolic diseases is now a well established concept. The scope of the Developmental Origins of Health and Disease has, however, widened and led to the identification of new targets of fetal programming, notably effects on reproductive function. Epidemiologic studies about maternal nutrition and effects on offsprings fertility are rare, but a link between impaired fetal growth, possibly caused by maternal malnutrition, and reproductive function, has been established. The methodologic limitations inherent to human epidemiologic studies can be complemented through the use of animal models, which enable experimental studies on maternal environment and its effect on reproductive functions of the offspring. Altogether, an interaction between inappropriate maternal nutrition (excess or reduced nutritional intake, micronutrient unbalance, or alcohol intake) and reproductive maturation of the offspring has been shown in a majority of experiments as summarized in this review. The exact processes through which maternal nutrition or maternal environment affect reproductive function in the offspring remain unclear but epigenetic modifications are a clear link. Further studies are needed to better understand the mechanisms involved, identify the crucial critical periods, and prevent or treat the adverse effects.

Dietary lipid and cholesterol induce ovarian dysfunction and abnormal LH response to stimulation in rabbits

Background/Aim Excess of fat intake is dramatically increasing in women of childbearing age and results in numerous health complications, including reproductive disorders. Using rabbit does as a biomedical model, the aim of this study was to evaluate onset of puberty, endocrine responses to stimulation and ovarian follicular maturation in females fed a high fat high cholesterol diet (HH diet) from 10 weeks of age (i.e., 2 weeks before normal onset of puberty) or a control diet (C diet). Methodology/Principal Findings Three experiments were performed, each including 8 treated (HH group) and 8 control (C group) does. In experiment 1, the endocrine response to Gonadotropin releasing hormone (GnRH) was evaluated at 13, 18 and 22 weeks of age. In experiment 2, the follicular population was counted in ovaries of adult females (18 weeks of age). In experiment 3, the LH response to mating and steroid profiles throughout gestation were evaluated at 18 weeks of age. Fetal growth was monitored by ultrasound and offspring birth weight was recorded. Data showed a significantly higher Luteinizing hormone (LH) response after induction of ovulation at 13 weeks of age in the HH group. There was no difference at 18 weeks, but at 22 weeks, the LH response to GnRH was significantly reduced in the HH group. The number of atretic follicles was significantly increased and the number of antral follicles significantly reduced in HH does vs. controls. During gestation, the HH diet induced intra-uterine growth retardation (IUGR). Conclusion The HH diet administered from before puberty onwards affected onset of puberty, follicular growth, hormonal responses to breeding and GnRH stimulation in relation to age and lead to fetal IUGR.

Is intracytoplasmic morphologically selected sperm injection effective in patients with infertility related to teratozoospermia or repeated implantation failure

OBJECTIVEnTo evaluate the potential benefit of intracytoplasmic morphologically selected sperm injection (IMSI) in patients selected for either severe teratozoospermia or repeated implantation failure after conventional intracytoplasmic sperm injection (ICSI).nnnDESIGNnProspective nonrandomized observational study.nnnSETTINGnUniversity hospital assisted reproduction unit.nnnPATIENT(S)nFour hundred seventy-eight patients were enrolled to evaluate ICSI and IMSI results for two indications. The first group (T) was composed of patients with severe teratozoospermia (<10% normal spermatozoa in fresh ejaculated and selected semen, according to David classification) and no or one previous ICSI failure. In the second group (IF), patients with at least two previous failed ICSI attempts were enrolled in absence of severe male factor (>10% normal spermatozoa in fresh ejaculated semen and >20% in selected sperm).nnnINTERVENTION(S)nICSI/IMSI, biologic, and clinical data collection.nnnMAIN OUTCOME MEASURE(S)nLive-birth rate (LBR).nnnRESULT(S)nIn group T, LBR was significantly higher when IMSI procedure was used compared with ICSI (38% [50/132] vs. 20% [25/126]). However, LBR observed in group IF was not significantly different between IMSI and ICSI procedures (21% [19/90] vs. 22% [28/130]).nnnCONCLUSION(S)nIMSI procedure is a valuable option for patients with severe teratozoospermia at their first or second attempts, but it does not improve pregnancy rate in patients with repeated ICSI failures in the absence of severe male factor.

In Subfertile Couple, Abdominal Fat Loss in Men Is Associated with Improvement of Sperm Quality and Pregnancy: A Case-Series

Background The impact of overweight among men of reproductive-age may affect fertility. Abdominal fat, more than body mass index, is an indicator of higher metabolic risk, which seems to be involved in decreasing sperm quality. This study aims to assess the relationship between abdominal fat and sperm DNA fragmentation and the effect of abdominal fat loss, among 6 men in subfertile couples. Methods Sperm DNA fragmentation, abdominal fat and metabolic and hormonal profiles were measured in the 6 men before and after dietary advices. Seminal oxidative stress and antioxidant markers were determined. Results After several months of a lifestyle program, all 6 men lost abdominal fat (patient 1: loss of 3 points of abdominal fat, patient 2: loss of 3 points, patient 3: loss of 2 points, patient 4: loss of 1 point, patient 5: loss of 4 points and patient 6: loss of 13 points). At the same time, their rate of sperm DNA fragmentation decreased: 9.5% vs 31%, 24% vs 43%, 18% vs 47%, 26.3% vs 66%, 25.4% vs 35% and 1.7% vs 25%. Also, an improvement in both metabolic (significant decrease in triglycerides and total cholesterol; pu200a=u200a0.0139) and hormonal (significant increase in testosterone/oestradiol ratio; pu200a=u200a0.0139) blood profiles was observed after following the lifestyle program. In seminal plasma, the amount of SOD2 has significantly increased (pu200a=u200a0.0139) while in parallel carbonylated proteins have decreased. Furthermore, all spouses got pregnant. All pregnancies were brought to term. Conclusion This study shows specifically that sperm DNA fragmentation among men in subfertile couples could be affected by abdominal fat, but improvement of lifestyle factor may correct this alteration. The effect of specific abdominal fat loss on sperm quality needs further investigation. The reduction of oxidative stress may be a contributing factor.

Body mass index is not associated with sperm-zona pellucida binding ability in subfertile males

Lifestyle factors, such as weight and nutritional status may affect male fertility, including sperm fertilization ability. The objective of this retrospective study was to evaluate the association between body mass index (BMI) and sperm-zona pellucida binding ability assessed according to the zona binding (ZB) test, which has been described to be a relevant diagnostic tool for the prediction of in vitro fertilization (IVF) ability. Three hundred and six male patients from couples diagnosed with primary idiopathic or mild male factor infertility were included. Correlations between BMI and semen parameters according to ZB test indices were assessed, together with frequencies of positive and negative tests across the BMI categories. In this selected population, BMI was not related to conventional semen parameters or sperm quality assessed according to the ability of spermatozoa to bind to the zona pellucida. The previously described poor outcomes of IVF procedures in cases of male obesity could be due to other sperm defects, such as alterations of sperm capacitation or acrosome reaction. The link between male BMI and biological outcomes during IVF procedures, such as fertilization rates, should be further evaluated.

A Review of Outcome Data concerning Children Born following Assisted Reproductive Technologies

Assisted reproductive technologies (ARTS) are used for more than 30 years to help infertile couples. Concerns about long-term health of children conceived following ART have led to start follow-up studies. Despite methodological limitations and discrepant results, many of the studies and meta-analyses have reported an increased risk of birth defects after ART. Etiologies may be multiple births, a major drawback of ART, parents subfertility, or technologies themselves. Prematurity and intrauterine growth retardation (IUGR) seem to cause most of the pathologies reported in ART children. Nevertheless, epigenetic disorders need to be followed up since increases of imprinting diseases were reported. Consequently, alteration of gametes and early embryo development with ART may have consequences on children health since periconceptional period is critical for long-term development. Yet general condition of most of children conceived with ART is reassuring, but long-term followup is still strongly needed.

Maternal high-fat diet induces follicular atresia but does not affect fertility in adult rabbit offspring.

Alterations to the metabolic environment in utero can have an impact on subsequent female reproductive performance. Here, we used a model of rabbits receiving a high-fat diet (H diet; 7.7% fat and 0.2% cholesterol) or a control diet (C diet; 1.8% fat, no cholesterol) from 10 weeks of age up to mating at 27 weeks and throughout gestation and lactation. At weaning at 5 weeks of age, F1 female offspring were placed on either C or H diet, resulting in a total of four groups C/C, C/H, H/C and H/H diet. Female offspring were mated between 18 and 22 weeks of age and euthanized at 28 days of gestation. A few days before mating and/or just before euthanasia, F1 female rabbits were fasted overnight, weighed, and blood sampled for steroids and biochemistry. Organs were weighed at euthanasia and the ovaries were collected. C/H and H/H F1 offspring had higher cholesterol and high-density lipoprotein plasma concentrations, together with a higher fat mass compared with C/C does, reflecting the effect of the postnatal diet; however, no effect of the antenatal diet was observed on most parameters. The number of primordial, primary and secondary follicles were not different between the groups, but a significantly higher number of atretic follicles was observed in the C/H (P<0.001) and in the H/C (P<0.001) compared with control C/C ovaries, demonstrating both an effect of prenatal and postnatal maternal nutrition. These data indicated that both maternal and postnatal high-fat diet may induce follicular apoptosis; however, in this model, the reproduction was not affected.

Impact of maternal hyperlipidic hypercholesterolaemic diet on male reproductive organs and testosterone concentration in rabbits.

The concept of Developmental Origins of Health and Disease initially stemmed from the developmental programming of metabolic diseases. Reproductive functions and fertility in adulthood may also be programmed during foetal development. We studied the impact of dietary-induced maternal hyperlipidaemia and hypercholesterolaemia (HH), administered at 10 weeks of age and throughout the gestation and lactation, on male reproductive functions of rabbit offspring. Male rabbits born to HH dams and fed a control diet had significantly lighter testes and epididymes compared with rabbits born to control dams at adulthood. No significant changes in sperm concentration, sperm DNA integrity and sperm membrane composition were observed, but serum-free testosterone concentrations were decreased in HH males. This study confirms the importance of maternal metabolic status for the development of male reproductive organs.

Delivery rates after elective single cryopreserved embryo transfer related to embryo survival

OBJECTIVEnThe objective of this study was to assess if eSCET (elective Single Cryopreserved Embryo Transfer) outcome is related to blastomere survival rate. The final objective was to avoid multiple pregnancies and offer the best chances to women to achieve pregnancy even during their frozen-thawed embryo transfer (FET) cycles.nnnSTUDY DESIGNnPatients were included in this prospective observational study if they met the following criteria: (i) women age <37 years old; (ii) IVF of ICSI cycle rank ≤2, (iii) eSET proposed during fresh embryo transfer cycle and (iv) ≥1 good quality cryopreserved embryos available (<20% fragmentation and 4-5 blastomeres at day-2 or 7-9 blastomeres at day-3). Live birth rates (LBR) were compared into eSCET groups according to embryo survival (partially damaged or intact transferred embryo).nnnRESULTSnWe observed among selected patients, that partial loss of blastomeres (1 blastomere for day-2 embryos, 1 or 2 blastomeres for day-3 embryos) following FET cycles did not affect LBR compared with intact embryo.nnnCONCLUSIONnThese results underline the relevance of eSCET as a strategy to reduce multiple pregnancies frequency without reducing LBR.