Adverse effects of hepatitis B virus on sperm motility and fertilization ability during IVF.

The consequences of hepatitis B virus (HBV) infection for fertility are still unclear. Spermatozoa with decreased motility have been reported in HBV-infected patients. It has been demonstrated in vitro that HBV S protein has adverse effects on human sperm function with consequences for fertilization. In a case-control study design, 32 IVF cycles in couples with male HBV infection were compared with 64 cycles in non-infected couples, matched for age, time period, cycle rank and sperm parameters on the day of oocyte retrieval. Sperm motility before selection was significantly reduced in the HBV group (36.3 ± 11.6% versus 45.3 ± 14.4%,P = 0.003). A low fertilization rate (LFR) was more frequently observed in the HBV group (34.4% versus 15.6%, P = 0.036) and was associated with a decreased number of embryos available for transfer, although embryo quality on day 2 or 3 was not different.Implantation and pregnancy rates were comparable between groups. This study shows that HBV has a deleterious effect on sperm motility in vivo and that couples whose male partner is infected have a higher risk of LFR after IVF, a risk which is independent from the initial sperm motility.

In vitro maturation of oocytes for preserving fertility in autoimmune premature ovarian insufficiency.

OBJECTIVE: To test whether in vitro maturation (IVM) of oocytes is an option for preserving the fertility of women diagnosed with premature ovarian insufficiency (POI). DESIGN: Case report. SETTING: University hospital. PATIENT(S): A 36-year-old amenorrheic patient was referred for fertility preservation (FP) counseling with a diagnosis of autoimmune POI. Serum follicle-stimulating hormone (21.0 and 36.3 mIU/mL) and luteinizing hormone (35.0 and 60.0 mIU/mL) levels taken 4 weeks apart were around the menopausal range. Although serum antimüllerian hormone level was low (0.76 and 0.65 ng/mL), total counts of antral follicles remained unexpectedly normal (24 and 22). Significant levels of serum antiperoxidase, anti-21-hydroxylase, and antiovary antibodies led to the diagnosis of autoimmune polyendocrinopathy. Due to the unknown time before follicular exhaustion, we undertook a FP program. INTERVENTION(S): After unsuccessful follicular growth following a trial of ovarian stimulation using recombinant follicle-stimulating hormone (300 IU/day for 10 days), we decided to try IVM of immature oocytes aspirated from the remaining antral-stage follicles. MAIN OUTCOME MEASURE(S): Obtention of immature oocyte capable of maturing in vitro in a context of acute ovarian dysfunction. RESULT(S): Two cycles of IVM were performed, leading, after human chorionic gonadotropin priming, to six and 10 cumulus-oocyte complexes recovered and four and eight metaphase II oocytes. Finally, after intracytoplasmic sperm injection, a total of eight cleavage-stage embryos were frozen. When the patient presented in the clinic 1 year later for reutilization of the cryopreserved embryos, thyroid and adrenal functions were controlled with levothyroxine and hydrocortisone. Endometrium was primed with 17ß-estradiol (2 mg/day, vaginally) for 14 days. Progesterone (600 mg/day, vaginally) was subsequently combined with E2. Two embryos were thawed and further transferred into the uterus. The patient became pregnant and uneventfully delivered two baby boys at term. CONCLUSION(S): We report the first pregnancy and live birth achieved using IVM for FP in a woman diagnosed with autoimmune POI. The confirmation of our results would lead to modification in the management of young women diagnosed with autoimmune POI, who are usually not considered candidates for FP and often referred for egg donation when seeking pregnancy.

Large genomic rearrangements in the hepatocyte nuclear factor-1beta (TCF2) gene are the most frequent cause of maturity-onset diabetes of the young type 5.

Maturity-onset diabetes of the young (MODY) 5 is caused by mutations in the TCF2 gene encoding the transcription factor hepatocyte nuclear factor-1beta. However, in 60% of the patients with a phenotype suggesting MODY5, no point mutation is detected in TCF2. We have hypothesized that large genomic rearrangements of TCF2 that are missed by conventional screening methods may account for this observation. In 40 unrelated patients presenting with MODY5 phenotype, TCF2 was screened for mutations by sequencing. Patients without mutations were then screened for TCF2 rearrangements by the quantitative multiplex PCR of short fluorescent fragments (QMPSF). Among the 40 patients, the overall detection rate was 70%: 18 had point mutations, 9 had whole-gene deletions, and 1 had a deletion of a single exon. Similar phenotypes were observed in patients with mutations and in subjects with large deletions. These results suggest that MODY5 is more prevalent than previously reported, with one-third of the cases resulting from large deletions of TCF2. Because QMPSF is more rapid and cost effective than sequencing, we propose that patients whose phenotype is consistent with MODY5 should be screened first with the QMPSF assay. In addition, other MODY genes should be screened for large genomic rearrangements.

Mutations and sequence variants in GDF9 and BMP15 in patients with premature ovarian failure.

BACKGROUND AND OBJECTIVE: Mutations in bone morphogenic protein 15 (BMP15) and growth/differentiation factor 9 (GDF9) lead to altered fertility in animal models. In the human, a heterozygous point mutation of BMP15 has been associated with premature ovarian failure (POF). SUBJECT AND METHODS: We have directly sequenced both genes in a cohort of 203 POF patients presenting with primary or secondary amenorrhea and high FSH levels and in a control population including 54 women with regular menstrual cycles who had at least one child. RESULTS: We have identified several heterozygous variants. One alteration in GDF9 (S186Y) and one in BMP15 (L148P) may have pathogenic effects as both positions are conserved in vertebrate species, ranging from the chicken to mammals. These variants were absent in the control samples. We also found synonymous and neutral substitutions. CONCLUSIONS: We propose that although mutations in BMP15 and GDF9 are not a major cause of ovarian insufficiency, they may be involved in POF.

Female hypofertility: collaboration between clinician and biologist.

Hypofertility is defined as the absence of conception after one year of trying. Women's exploration needs biologist attendance for the ovarian reserve evaluation and radiologist attendance for the exploration of the uterus, the fallopian tubes and the ovary. The management of women's treatment as ovarian stimulation combine hormonal levels and transvaginal ultrasonography during all the treatment. The collaboration between clinician and biologist is necessary for the diagnosis and during women's infertily treatment.