Isabelle Cedrin-Durnerin

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)).

Age and ovarian reserve are distinct predictive factors of cycle outcome in low responders.

The respective roles of age and ovarian reserve in predicting IVF outcome do not seem to be equivalent, as a high pregnancy rate seems to be preserved in the youngest women, despite low ovarian recruitment. The purpose of this study was to analyse the outcome of IVF/intracytoplasmic sperm injection (ICSI) procedures according to both age and ovarian reserve of patients with a low ovarian response to stimulation. A total of 163 IVF/ICSI cycles selected by a low response were analysed. The IVF outcome differed according to the womens age, with a cut-off value at 36 years. While the number of transferred embryos was similar, the pregnancy rate (PR) was 14.6% in younger patients but 4.9% (P < 0.04) in older ones. An elevated FSH was constantly associated with a poor cycle outcome. In contrast, when the FSH was normal, PR was significantly higher (P < 0.05) in women aged <36 (23.8%) than in women aged > or =36 (6.5%). This study shows that assisted reproduction outcome in women with a low ovarian response is primarily dependent on the ovarian status. The negative influence of age is relevant in patients with normal FSH. Therefore, even if the ovarian response to stimulation is low, patients aged <36 years with a normal FSH should proceed to oocyte retrieval.

A comparative study of high fixed-dose and decremental-dose regimens of gonadotropins in a minidose gonadotropin-releasing hormone agonist flare protocol for poor responders.

Selecting the most effective protocol for an IVF procedure is still a major challenge for women known as poor responders to controlled ovarian hyperstimulation (COH). Indeed, using the standard long-term GnRHagonist (GnRH-a) protocol in these patients requires a large amount of gonadotropins to obtain development of only few follicles. Moreover, the pregnancy rate (PR) remains inappropriately low because of poor oocyte and embryo quality. It was suggested that poor responders may take advantage of the initial endogenous gonadotropin “flare” induced by GnRH-a (1). Moreover, lowering the dose of agonist in short-term GnRH-a protocols may prove effective to decrease the requirement for gonadotropins and to induce an initial gonadotropin release with subsequent LH suppression (2).

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

OBJECTIVE To 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). DESIGN Prospective nonrandomized observational study. SETTING University hospital assisted reproduction unit. PATIENT(S) Four 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). INTERVENTION(S) ICSI/IMSI, biologic, and clinical data collection. MAIN OUTCOME MEASURE(S) Live-birth rate (LBR). RESULT(S) In 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]). CONCLUSION(S) IMSI 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.

Impact of endogenous luteinizing hormone serum levels on progesterone elevation on the day of human chorionic gonadotropin administration

OBJECTIVE To assess the relationship between endogenous LH serum levels after GnRH analogue administration and serum P elevation on the day of hCG administration (P hCG). DESIGN Retrospective study. SETTING Reproductive medicine center in a university hospital. PATIENT(S) A total of 708 patients undergoing a GnRH agonist or antagonist protocol for IVF intracytoplasmic sperm injection. INTERVENTION(S) Controlled ovarian stimulation. MAIN OUTCOME MEASURE(S) Serum P values according to GnRH analogue; correlation between serum LH measurements and P hCG values. RESULT(S) Serum P hCG values were significantly lower following the GnRH antagonist than agonist protocol. A positive correlation between serum P hCG and LH area under the curve or day 6 LH values was found in the GnRH agonist group and between P hCG and LH hCG levels in both GnRH analogue regimens. With multivariate analysis, P hCG values were positively correlated with serum E(2) levels on hCG administration day and with the total FSH dose in both GnRH analogue-treated groups. Additionally, the correlation between serum P hCG and LH hCG values was positive in patients treated with the GnRH agonist protocol. CONCLUSION(S) The lower serum P levels on hCG administration day following the GnRH antagonist protocol are mainly explained by lower granulosa cell steroidogenic activity. The correlation with serum LH hCG values was positive in the GnRH agonist-treated group.

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; p = 0.0139) and hormonal (significant increase in testosterone/oestradiol ratio; p = 0.0139) blood profiles was observed after following the lifestyle program. In seminal plasma, the amount of SOD2 has significantly increased (p = 0.0139) 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.

Pretreatment with estrogen does not affect IVF-ICSI cycle outcome compared with no pretreatment in GnRH antagonist protocol: a prospective randomized trial

OBJECTIVE To assess effects of estrogen pretreatment in GnRH antagonist protocol. DESIGN Prospective, randomized multicenter study. SETTING Ten private or university-based centers. PATIENT(S) A total of 472 patients undergoing IVF/ICSI. INTERVENTION(S) Randomization by sealed envelopes to receive 17β-estradiol (4 mg/d) or no pretreatment before daily recombinant FSH administration started on the first day of estrogen discontinuation or on cycle day 2 in nonpretreated women. MAIN OUTCOME MEASURE(S) The primary outcome measure was the number of retrieved oocytes. Secondary efficacy variables included total FSH dose, cycle duration, and outcome. RESULT(S) The mean numbers of retrieved oocytes (10.9 ± 5.7 vs. 10.2 ± 5.6) and obtained embryos (5.5 ± 3.7 vs. 4.8 ± 3.7) were not significantly different between women allocated to estrogen pretreatment (n = 238) and no pretreatment (n = 234). Total FSH amount (1,557 ± 408 vs. 1,389 ± 347 IU) and stimulation duration (10.8 ± 1.4 vs. 10.0 ± 1.5 days) were slightly but significantly increased in pretreated patients. Positive pregnancy tests, ultrasound pregnancy rate, and delivery rate per cycle were similar (36%, 33%, and 26.6%, respectively, vs. 38.2%, 35.4%, and 30%). CONCLUSION(S) These data confirm that estrogen pretreatment is associated with requirement of higher FSH doses and longer duration of stimulation without any significant increase in the number of retrieved oocytes. However, estrogen does not affect cycle outcome and therefore might be used in clinical practice for programming IVF retrievals during working days. CLINICAL TRIALS REGISTRATION NUMBER NCT01489852.

Assessment of theca cell function prior to controlled ovarian stimulation: the predictive value of serum basal/stimulated steroid levels

BACKGROUND Serum androgen levels correlate with ovarian sensitivity to follicle-stimulating hormone (FSH) but in practice, standard baseline serum testosterone (T) levels prior to in-vitro fertilization (IVF) may not be the most appropriate marker for determination. METHODS Infertile women enrolled in an IVF programme were included in this study. Serum T and Delta4-androstenedione (A), and the androgen precursor 17-hydroxyprogesterone (17-OHP) were measured before and 24 h after a gonadotrophin-releasing hormone agonist stimulation test (GAST). An early follicular phase antral follicle count (AFC) was also performed. Patients were subsequently enrolled in a long gonadotrophin-releasing hormone agonist protocol with a standard FSH dose (150 IU) for 7 days to assess the association between androgen levels and ovarian responsiveness to FSH. RESULTS The GAST elicited a significant increase in serum androgen levels that was well correlated with AFC. 17-OHP showed the greatest response to GAST and strongest correlation with AFC. The 17-OHP response to GAST differentiated patients with high ovarian reserve (OR) from those with low or normal OR as assessed by AFC, whereas only the estradiol response could differentiate those with low AFC. GAST-stimulated serum levels of 17-OHP were also correlated with ovarian response to FSH. Using receiver operating characteristic curve analysis, stimulated 17-OHP levels were predictive of the ovarian response to controlled ovarian stimulation, with similar power to that observed with AFC but lower power than with anti-Müllerian hormone. CONCLUSIONS Serum androgen levels following GAST are correlated with AFC and ovarian response to FSH. Serum T is a less sensitive marker of theca cell function than 17-OHP.

Fertility preservation in Turner syndrome

Premature ovarian insufficiency is a relatively rare condition that can appear early in life. In a non-negligible number of cases the ovarian dysfunction results from genetic diseases. Turner syndrome (TS), the most common sex chromosome abnormality in females, is associated with an inevitable premature exhaustion of the follicular stockpile. The possible or probable infertility is a major concern for TS patients and their parents, and physicians are often asked about possible options to preserve fertility. Unfortunately, there are no recommendations on fertility preservation in this group. The severely reduced follicle pool even during prepubertal life represents the major limit for fertility preservation and is the root of numerous questions regarding the competence of gametes or ovarian tissue crybanked. In addition, patients suffering from TS show higher than usual rates of spontaneous abortion, fetal anomaly, and maternal morbidity and mortality, which should be considered at the time of fertility preservation and before reutilization of the cryopreserved gametes. Apart from fulfillment of the desire of becoming genetic parents, TS patients may be potential candidates for egg donation, gestational surrogacy, and adoption. The present review discusses the different options for preserving female fertility in TS and the ethical questions raised by these approaches.

Biological predictive criteria for clinical pregnancy after elective single embryo transfer

In this prospective observational study, the onset of a clinical pregnancy after elective single embryo transfer (eSET) was significantly associated with: 1) the womans age as well as the number of good- and top-quality embryos; and 2) the day of the embryo transfer (day 3>day 2). Good-quality embryos had the same ability to implant, regardless of the zygotic score, the day 1 early cleavage rate, the fragmentation degree, and the top-quality assessment, specifying the eligibility criteria for eSET.