The continuum of ovarian response leading to BIRTH, a real world study of ART in Spain.

BACKGROUND: The first biosimilar of recombinant follicle stimulating hormone (rFSH) launched in Europe was Bemfola® in 2014 following a clinical development programme demonstrating efficacy and safety to the satisfaction of the European Medicines Agency. Since then the increasing use of biosimilar rFSH has provided the opportunity to study both effectiveness across the whole population and the variation of rFSH use during routine clinical care in a real-world setting in Spain. METHODS: This is a real-world study of 1222 women treated in 26 assisted reproduction treatment centres throughout Spain providing experience of the use of a biosimilar recombinant follicle stimulating hormone in four distinct populations. The four populations studied were poor responders, suboptimal responders, normal responders and oocyte donors. The primary endpoint was the total number of oocytes retrieved. Secondary endpoints included number of days of rFSH stimulation, total dose of rFSH administered, number of MII oocytes, number of fertilized oocytes, quality of embryos, number of embryos transferred, implantation rates, clinical pregnancy rates following embryo transfer, number of multiple pregnancies and number of serious adverse reactions, including moderate-to-severe OHSS. RESULTS: Differences were seen across the populations both in the characteristics of the women and ART outcomes suggestive of a continuum of fertility prognosis. In the poor responders, suboptimal responders, normal responders and oocyte donor populations the mean age in years was 39.9 (±SD 3.4), 38.4 (±SD 2.9), 34.4 (±SD 3.3) and 26 (±SD 4.6) respectively and number of oocytes retrieved was 4.1 (±SD 2.7), 8.6 (±SD 6.0), 12.2 (±SD 7.2) and 19.5 (±SD 9.5) respectively. The proportion of embryos graded as best quality was 18.5%, 33.0% and 43.8%, and graded as worst quality was 20.4%, 5.8% and 5.8% for poor responders, suboptimal responders and normal responders respectively. In a similar pattern, for poor responders, suboptimal responders and normal responders the implantation rates were 16.0%, (8/50), 22.4% (49/219), 30.6% (97/317) respectively and clinical pregnancy rates were 23.2% (10/43), 30.4% (59/194) and 37.0% (114/308) respectively. Adverse events were reported in only 7 of 1222 women (0.6%). CONCLUSIONS: Overall the results were consistent with the national ART results reported for Spain, hence this study provides reassurance of the clinical effectiveness of a biosimilar rFSH used in a real world setting. TRIAL REGISTRATION: ClinicalTrials.gov identifier - NCT02941341.

Normalized second and fourth finger lengths in male and female partners and IVF cycle outcomes.

RESEARCH QUESTION: Hox genes are involved in limb formation during normal embryological development. Their modulation by circulating maternal oestrogens and androgens determines the length of the second and fourth fingers of the adult hand. Do these same intrauterine hormone levels also determine fertility outcomes in the adult? DESIGN: To study the association between the length of the second and fourth fingers of both partners undergoing IVF (as a surrogate of their previous intrauterine exposure to oestrogens and androgens) with treatment outcome after IVF, data corresponding to 256 IVF cycles were analysed. Finger length was normalized to the individual height. RESULTS: In the female partner, a longer normalized second finger length of the left (2DLN) hand, reflecting a high intrauterine exposure to oestrogens, was independently and significantly (P = 0.011) associated with obtaining at least one top-quality embryo in a multivariate model. Conversely, in the male partner a longer normalized fourth finger length of the left hand (4DLN), reflecting a high intrauterine exposure to androgens, was independently and significantly (P = 0.032) associated with obtaining at least one top-quality embryo in the same multivariate model. In the female partner, 2DLN was inversely and significantly (P = 0.01) associated with achievement of pregnancy. CONCLUSIONS: Intrauterine exposure to high levels of oestrogens and androgens in females and males, respectively, predisposes to the production of higher-quality embryos under in-vitro conditions during adulthood. Paradoxically, this also seems to result in a lower pregnancy rate.

Polycystic ovary syndrome throughout a woman's life.

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among reproductive-aged women and the main cause of infertility due to anovulation. However, this syndrome spans the lives of women affecting them from in-utero life until death, leading to several health risks that can impair quality of life and increase morbidity and mortality rates. Fetal programming may represent the beginning of the condition characterized by hyperandrogenism and insulin resistance which leads to a series of medical consequences in adolescence, adulthood, and old age. Menstrual and fertility problems evolve into metabolic complications as age advances. An early and precise diagnosis is important for an adequate management of PCOS, especially at the extreme ends of the reproductive lifespan. However, many different phenotypes are included under the same condition, being important to look at these different phenotypes separately, as they may require different treatments and have different consequences. In this way, PCOS exhibits a great metabolic complexity and its diagnosis needs to be revised once again and adapted to recent data obtained by new technologies. According to the current medical literature, lifestyle therapy constitutes the first step in the management, especially when excess body weight is associated. Pharmacotherapy is frequently used to treat the most predominant manifestations in each age group, such as irregular menses and hirsutism in adolescence, fertility problems in adulthood, and metabolic problems and risk of cancer in old age. Close surveillance is mandatory in each stage of life to avoid health risks which may also affect the offspring, since fetal and post-natal complications seem to be increased in PCOS women.

Strategies to manage refractory endometrium: state of the art in 2016.

The endometrium is one of a number of factors involved in achieving optimal outcomes after assisted reproductive treatment. Owing to its "passive" growth following adequate ovarian stimulation, it has received virtually no attention. Only when either endometrial thickness or ultrasonographic pattern seem inadequate have different strategies been assessed to try to improve it, especially in those cases where it seems difficult or impossible to make it grow. The objective of this review is to summarize the different strategies that have been investigated in patients with inadequate endometrium, to attempt to provide solid evidence of therapies that may be beneficial and to move away from empirism. A review of the existing literature was performed by searching MEDLINE, EMBASE, Cochrane library and Web of Science for publications in English related to refractory endometrium. Most current treatments are based on anecdotal cases and not on solid data, although worldwide many doctors and patients use them. In conclusion, this review found that it is not easy to provide a pragmatic, evidence-based approach to help physicians and patients confused by the available data on how to improve a poor endometrium. Honest balanced information provided to our patients is the best that we can do.