The effectiveness of GnRH agonists as fertility-preserving agents is debatable. A thorough literature search has found insufficient evidence to show that GnRH agonist co-treatment is effective in protecting the ovary from the damage of chemotherapy. A large randomized controlled trial with adequate follow-up is needed.

Empty follicle syndrome is a condition in which no oocytes are retrieved after an apparently adequate ovarian response to stimulation and meticulous follicular aspiration. It is a rare condition of obscure etiology. A patient with primary infertility who underwent seven assisted reproductive technique cycles is described. In spite of a satisfactory ovarian response, aspiration yielded no oocytes in four cycles and 1-4 low quality oocytes in three cycles. In the index treatment cycle, ovulation was triggered using GnRH agonist 40 h prior to ovum pickup and hCG was added 6 h after the first trigger. Eighteen oocytes were recovered, of which 16 were mature and were inseminated by ICSI. Two embryos were transferred 48 h after aspiration and nine embryos were cryopreserved. The patient conceived and delivered a healthy boy at 38 weeks of gestation. The literature is reviewed and possible etiologies and treatment options of this enigmatic syndrome are suggested.

Primary Ovarian Insufficiency (POI) affects ~1% of women under forty. Exome sequencing of two Finnish sisters with non-syndromic POI revealed a homozygous mutation in FANCM, leading to a truncated protein (p.Gln1701*). FANCM is a DNA-damage response gene whose heterozygous mutations predispose to breast cancer. Compared to the mother's cells, the patients' lymphocytes displayed higher levels of basal and mitomycin C (MMC)-induced chromosomal abnormalities. Their lymphoblasts were hypersensitive to MMC and MMC-induced monoubiquitination of FANCD2 was impaired. Genetic complementation of patient's cells with wild-type FANCM improved their resistance to MMC re-establishing FANCD2 monoubiquitination. FANCM was more strongly expressed in human fetal germ cells than in somatic cells. FANCM protein was preferentially expressed along the chromosomes in pachytene cells, which undergo meiotic recombination. This mutation may provoke meiotic defects leading to a depleted follicular stock, as in Fancm-/-mice. Our findings document the first Mendelian phenotype due to a biallelic FANCM mutation.

No abstract