Recurrent implantation failure refers to failure to achieve a clinical pregnancy after transfer of at least four good-quality embryos in a minimum of three fresh or frozen cycles in a woman under the age of 40 years. The failure to implant may be a consequence of embryo or uterine factors. Thorough investigations should be carried out to ascertain whether there is any underlying cause of the condition. Ovarian function should be assessed by measurement of antral follicle count, FSH and anti-Mu¨llerian hormone. Increased sperm DNA fragmentation may be a contributory cause. Various uterine pathology including fibroids, endometrial polyps, congenital anomalies and intrauterine adhesions should be excluded by ultrasonography and hysteroscopy. Hydrosalpinges are a recognized cause of implantation failure and should be excluded by hysterosalpingogram; if necessary, laparoscopy should be performed to confirm or refute the diagnosis. Treatment offered should be evidence based, aimed at improving embryo quality or endometrial receptivity. Gamete donation or surrogacy may be necessary if there is no realistic chance of success with further IVF attempts.

The study was conducted to evaluate if the diagnosis and treatment of intrauterine lesions with office hysteroscopy is of value in improving the pregnancy outcome in patients with recurrent in-vitro fertilization and embryo transfer failure. Four hundred and twenty-one patients who had undergone two or more failed IVF-embryo transfer cycles were prospectively randomized into two groups. Group I (n = 211) did not have office hysteroscopic evaluation, Group II (n = 210) had office hysteroscopy. The patients who had normal hysteroscopic findings were included in Group IIa (n = 154) and patients who had abnormal hysteroscopic findings were included in Group IIb (n = 56). Intrauterine lesions diagnosed were operated during the office procedure. Fifty-six (26%) patients in Group II had intrauterine pathologies and the treatment was performed at the same time. No difference existed in the mean number of oocyte retrieved, fertilization rate, number of embryos transferred or first trimester abortion rates among the patients in groups. Clinical pregnancy rates in Group I, Group IIa and Group IIb were 21.6%, 32.5% and 30.4% respectively. There was a significant difference in the clinical pregnancy rates between patients in Group I and Group IIa (21.6% and 32.5%, P = 0.044, respectively) and Group I and Group IIb (21.6% and 30.4%, P = 0.044, respectively). There was no significant difference in the clinical pregnancy rate of patients in Groups IIa and IIb. Patients with normal hysterosalpingography but recurrent IVF-embryo transfer failure should be evaluated prior to commencing IVF-embryo transfer cycle to improve the clinical pregnancy rate.

The study was conducted to investigate the effect of conservative surgery of ovarian endometriomas before an ICSI cycle. Ninety-nine patients with endometriomas who were referred to an intracytoplasmic sperm injection (ICSI) cycle were enrolled in the study. The patients were prospectively randomized into two groups; group I (49 patients) underwent conservative ovarian surgery before the ICSI cycle and group II (50 patients) underwent the ICSI cycle directly. The stimulation was started 3 months after the operation in group I and directly in group II. In the ovarian surgery group, stimulation was significantly longer (14.0 days in group I and 10.8 days in group II; P = 0.001), total recombinant FSH dose was significantly higher (4575 IU in group I and 3675 IU in group II; P = 0.001), and mean number of mature oocytes was significantly lower (7.8 in group I and 8.6 in group II; P = 0.032). There was no difference in terms of fertilization (86% in group I and 88% in group II), implantation (16.5% in group I and 18.5% in group II) and pregnancy rates (34% in group I and 38% in group II). Ovarian surgery resulted in longer stimulation, higher FSH requirement and lower oocyte number, but fertilization, pregnancy and implantation rates did not differ between the groups.

Array CGH is becoming an important clinical assay for unbalanced chromosome abnormalities whether cells grow in culture or not and in cases of analysis on one or few cells.

To date, mutations in two genes, SPATA16 and DPY19L2, have been identified as responsible for a severe teratozoospermia, namely globozoospermia. The two initial descriptions of the DPY19L2 deletion lead to a very different rate of occurrence of this mutation among globospermic patients. In order to better estimate the contribution of DPY19L2 in globozoospermia, we screened a larger cohort including 64 globozoospermic patients. Twenty of the new patients were homozygous for the DPY19L2 deletion, and 7 were compound heterozygous for both this deletion and a point mutation. We also identified four additional mutated patients. The final mutation load in our cohort is 66.7% (36 out of 54). Out of 36 mutated patients, 69.4% are homozygous deleted, 19.4% heterozygous composite and 11.1% showed a homozygous point mutation. The mechanism underlying the deletion is a non-allelic homologous recombination (NAHR) between the flanking low-copy repeats. Here, we characterized a total of nine breakpoints for the DPY19L2 NAHR-driven deletion that clustered in two recombination hotspots, both containing direct repeat elements (AluSq2 in hotspot 1, THE1B in hotspot 2). Globozoospermia can be considered as a new genomic disorder. This study confirms that DPY19L2 is the major gene responsible for globozoospermia and enlarges the spectrum of possible mutations in the gene. This is a major finding and should contribute to the development of an efficient molecular diagnosis strategy for globozoospermia.