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The effect of a raised body mass index (BMI) on the outcome of assisted reproduction technology (ART) still represents a controversial issue. Even less clear is whether BMI acts with a potential detrimental effect on IVF outcomes via a deleterious effect on innate quality of oocytes or on the environmental milieu within the uterus. With the aim to better understand the mechanisms underlying the potential deleterious effect of an increased BMI on IVF outcomes, we have evaluated the effects of female BMI on number and quality of retrieved oocytes, fertilization rate, embryo score and incidences of ongoing pregnancy and live births among couples undergoing IVF in an Italian population. Data from 1602 women who underwent their first IVF cycle were retrospectively analyzed. A significantly reduced percentage of mature oocytes when comparing obese (BMI ≥ 30 kg/m2) and normal-weight patients (BMI = 18.50–24.99 kg/m2) was found. After adjusting for maternal age and other confounders, odds for ongoing pregnancy rate showed no differences across different BMI categories. However, a significant increased odds ratio (OR) could be observed for miscarriage rate in patients with BMI ≥ 25 (OR = 2.5; p = 0.04). These results should be taken into account in order to define optimal strategies for overweight and obese patients referring to ART procedures.

Subtle alterations in coagulation and fibrinolysis have been recently reported in patients with endometriosis supporting a potential hypercoagulable status associated with the disease. This cross-sectional study aimed at evaluating some variables of coagulation status and inflammatory markers in women with endometriosis. A total of 314 women who underwent surgery were considered. The case group (n = 169) included patients with a surgical diagnosis of endometriosis, at any stage of disease. The control group (n = 145) included women with a surgical diagnosis of benign gynecologic pathology. No difference was found for thrombin time, International Normalized Ratio (INR), platelet count, neutrophil count, lymphocyte count, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio (PLR) between women with endometriosis and controls. Conversely, patients with endometriosis had significantly shortened activated partial thromboplastin time (APTT) when compared to controls (1.08 ± 0.06 and 1.12 ± 0.19, respectively; P < .01). In the subgroup analysis, women with ovarian endometriosis had significantly shortened APTT values in comparison to women without this form and women with stage I to II endometriosis had significantly shorter APTT values and higher PLR than those with stage III to IV disease. In multivariate logistic regression analysis, after controlling for potential confounders, a shortened APTT remained associated with the disease. Activated partial thromboplastin time is shorter in women with endometriosis but still in the normal range. The evidence is insufficient to foresee a possible use of APTT as a diagnostic marker and to claim a crucial role of a systemic hypercoagulable state in the origin of the disease. A role of the local coagulation system in the pathogenesis of the disease cannot be excluded.

Serum TSH increased considerably during COH in adequately treated hypothyroid women undergoing IVF. We suggest strictly monitoring these women during IVF cycles and, if necessary, promptly adjusting the levothyroxine dose. This is the most pragmatic approach but, to date, it is not supported by clinical evidence. Further studies aimed at clarifying the most suitable therapeutic strategy are thus warranted.

The use of long-acting recombinant FSH in random-start protocols for fertility preservation appears to be a valuable option.

Uterine fibroids are the most common gynecologic benign tumors. Studies supporting a strong pregnancy-related growth of leiomyomas generally claimed a crucial role of sex steroid hormones. However, sex steroids are unlikely the unique actors involved as estrogen and progesterone achieve a pick serum concentration in the last trimester while leiomyomas show a typical increase during the first trimester. Given the rapid exponential raise in serum human Chorionic Gonadotrophin (hCG) at the beginning of gestation, we conducted a review to assess the potential role of hCG in the striking growth of leiomyomas during initial pregnancy. Fibroid growth during initial pregnancy seems to correlate to the similar increase of serum hCG levels until 12 weeks of gestation. The presence of functional Luteinizing Hormone/human Chorionic Gonadotropin (LH/hCG) receptors was demonstrated on leiomyomas. In vitro treatment of leiomyoma cells with hCG determines an up to 500% increase in cell number after three days. Expression of cyclin E and cyclin-dependent kinase 1 was significantly increased in leiomyoma cells by hCG treatment. Moreover, upon binding to the receptor, hCG stimulates prolactin secretion in leiomyoma cells, promoting cell proliferation via the mitogen-activated protein kinase cascade. Fibroid enlargement during initial pregnancy may be regulated by serum hCG.

BackgroundVitamin D plays an important role in human physiology and pathology. The receptor for vitamin D regulates 0.5–5% of the human genome. Accordingly, vitamin D insufficiency has been shown to increase the risk of several diseases. In recent years, based on growing evidence, on a role of vitamin D has been also postulated in reproductive health both in animals and humans, especially in female fertility female fertility. In vitro fertilization success was shown to be higher in women with appropriate reserves of vitamin D. However a causal relation has not been demonstrated and randomized controlled trials testing the effectiveness of vitamin D supplementation in IVF are warranted.MethodsThis is a multicenter randomized double blinded placebo controlled study aimed at determining the benefits of vitamin D [25(OH)D] supplementation in improving clinical pregnancy rate in women undergoing IVF. Eligible women with a serum level of 25-hydroxyvitamin D [25(OH)D] < 30 ng/ml will be randomized. Recruited women will be given the drug (either 600,000 IU of 25(OH) D or placebo in a single oral administration) at the time of randomization. Two centres will participate and the sample size (700 women) is foreseen to be equally distributed between the two. Patients will be treated according to standard IVF protocols.DiscussionThe primary aim of the study is the cumulative clinical pregnancy rate per oocyte retrieval. Clinical pregnancy is defined as the presence of at least one intrauterine gestational sac with viable foetus at first ultrasound assessment (3 weeks after a positive human chorionic gonadotropin [hCG] assessment). Secondary outcomes include: 1) clinical and embryological variables; 2) oocyte and endometrium quality at a molecular level. To investigate this latter aspect, samples of cumulus cells, follicular and endometrial fluids will be obtained from a subgroup of 50 age-matched good-prognosis cases and controls.Trial registrationThe protocol was included in EudraCT on 22nd September 2015 with the registration number assigned ‘2015-004233-27’; it was submitted through the database of the Italian “Osservatorio Nazionale della Sperimentazione Clinica (OsSC)” - (National Monitoring Centre of Clinical Trials) to the National Competent Authority on 8th March 2016 and approved on 23rd June 2016.

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