Postponement of child bearing and maternal age at first pregnancy are on the rise, contributing considerably to an increase in age-related infertility and the demand for assisted reproductive technologies (ART) treatment. This brings to the infertility clinics many women with low ovarian reserve and poor ovarian response (POR) to conventional stimulation. The Bologna criteria were released to standardize the definition of POR and pave the way for the formulation of evidence-based, efficient modalities of treatment for women undergoing IVF-ET. More than four years have passed since the introduction of these criteria and the debate is still ongoing whether a revision is due. Women with POR comprise several sub-groups with diverse baseline distinctiveness, a major issue that has fueled the discussion. Although antral follicle count (AFC) and anti-Müllerian hormone (AMH), are considered good predictors of ovarian reserve, their threshold values are still not universally standardized. Different definitions for sonographic AFC and diverse assays for AMH are held responsible for this delay in standardization. Adding established risk factors to the criteria will lead to more reliable and reproducible definition of a POR, especially in young women. The original criteria did not address the issue of oocyte quality, and the addition of risk factors may yield specific associations with quality vs. quantity. Patient’s age is the best available criterion, although limited, to predict live-birth and presumably oocyte quality. High scale studies to validate these criteria are still missing while recent evidence raises concern regarding over diagnosis.

BACKGROUND: Overgrowth of bacteria in the birth canal is associated with an increased risk of late miscarriage, preterm labour, post-partum endometritis and low birthweight. Conception rates in assisted reproduction treatments (ART) remain frustratingly low. We examined whether the nature of bacterial flora, found in the uterine cervical canal at embryo transfer, is associated with the rate of conception in ART. METHODS: We sampled for bacteriological culture the cervical canal of 204 patients who underwent embryo transfer. Of these, 139 (68%) were of fresh embryos, following recent vaginal oocyte retrieval and prophylactic antibiotic therapy, and 65 (32%) of frozen–thawed embryos, without any vaginal intervention in the preceding days. Bacteriological work-up included identification, colony count and antibiotic susceptibility profile. Conception was correlated with bacterial type and colony count. RESULTS: In 75 patients (36.8%) sterile cervical cultures or lactobacillus were recorded. Of these 75 patients, 23 (30.7%) conceived, whereas among the 129 in whom any pathogenic micro-organism was recovered only 21 (16.3%) conceived (P = 0.002). No difference in colonization was found between women who underwent frozen–thawed versus fresh embryo transfer (57 and 67% respectively). Any Gram-negative colonization was associated with no conception. All Gram-positive, and 90% of the Gram-negative bacteria, were sensitive to augmentin. CONCLUSIONS: Failure to conceive in ART is significantly associated with bacterial colonization of the uterine cervix.

Propofol, frequently used for i.v. induction of anaesthesia in assisted reproduction procedures, has been suspected of damaging oocytes. Concentrations of propofol have recently been shown to increase in follicular fluid during oocyte retrieval. Our study was designed to assess whether exposure to increasing concentrations of propofol has a measurable effect on in-vitro fertilization, cleavage and embryo development. A cohort of 130 women underwent i.v. anaesthesia using propofol and fentanyl. Time of anaesthesia from i.v. injection of propofol was measured, as were the doses of the two drugs. In 32 women expected to have more than 15 oocytes retrieved, first, middle and last oocytes were cultured separately. The mean time from i.v. injection to first follicle aspiration was 200 s. The mean time for the aspiration of each additional oocyte was 17.6 s. In 10 out of 11 cases where follicular fluid concentrations of propofol were measured, there was an increase from the first to the last follicle, but no difference was found in the ratio of mature to immature oocytes. Nor were any differences found in fertilization, cleavage and embryo cell number. In so far as in-vitro development reflects embryo quality, we conclude that the time elapsed between retrieval of the first and last oocyte does not affect oocyte quality.

Hyperandrogenic anovulation is characterized by polycystic appearance of the ovaries, elevated free serum testosterone with decreased concentrations of serum sex hormone binding globulin, an increased ratio of luteinizing hormone to follicle stimulating hormone and varying degrees of insulin resistance. We hypothesize that this is the result of variably increased 'ovarian androgenic insulin responsiveness' acting in combination with body mass. Women who develop hyperandrogenism and anovulation when lean (having normal serum insulin concentrations) represent the more severely affected individuals, whereas those who can resume ovulation by losing weight (and lowering their elevated serum insulin) represent a milder form. The tendency of these women to develop ovarian hyperstimulation syndrome despite hypophyseal desensitization suggests a primary ovarian defect which is apparently more pronounced in lean subjects. The unique ability of surgical damage to the ovary to induce ovulation, raises the possibility that inflammatory-like tissue remodelling has a major role in rescuing follicles from androgen-induced atresia. Approaches that may facilitate the study of this possible mechanism may include examination of in-vitro perfused, post-surgery mammalian ovaries and the elucidation of signal transduction mechanism(s) of insulin in the ovary, with special reference to cells emanating from affected women.

Sensitivity to macrocyclic lactones, which are commonly used in veterinary clinics, was first found in Rough Collies, and was attributed in 2001 to a 4 bp deletion in the MDR1 gene. The list of affected breeds currently includes 13 breeds. Researchers from different countries and continents examined the allelic frequencies of the nt230(del4) MDR1 mutation, emphasizing the clinical importance of this test not only to mutation-prone dogs, but also to their crosses and mongrels, since treatment of a deletion carrier with these compounds may lead to its death. In this study, the allelic frequencies of nt230(del4) MDR1 mutation in affected breeds, their crosses, unrelated pure breeds and mongrels are reported for the state of Israel (n = 1416 dogs). The Israeli data were compared with reports from the US, Europe, UK, Australia and Japan. The allelic frequencies of nt230(del4) MDR1 mutation in Israel for Australian, Swiss and German Shepherds (31%, 17% and 2.4%, respectively) are similar to the corresponding frequencies worldwide, much higher for Border Collies (4.8%), twice lower for Rough Collies (28%, compared to 55% or more elsewhere), and ~1% for mongrels. The frequencies for crosses of Australian Shepherd and Border Collies in Israel are 4 and 1.6 times lower, respectively, compared to the frequencies for the respective pure breeds. This work, that for the first time presents the frequency of nt230(del4) MDR1 mutation in Israel, along with a worldwide survey, has implications for clinicians, owners and breeders of sheepdogs and their crosses and supports the need for extra care in treatment and in future breeding. Of note, the relative proportion of affected breeds, in the overall tested dogs, might be higher than their actual proportion in Israel due to directed samples collection by veterinarians for clinical purposes, as these are mainly limited to certain affected breeds or dogs that resemble them.