The effect of vitrified-warmed blastocyst transfer on postnatal growth: a 1-year follow-up questionnaire study.

RESEARCH QUESTION: Is postnatal growth of singletons aged 12 months born after vitrified-warmed blastocyst transfer (frozen embryo transfer [FET]) different from children born after fresh blastocyst transfer? DESIGN: A retrospective cohort study conducted at a single university-affiliated obstetrics and fertility centre between 2014 and 2016. Women who underwent fresh transfer or FET at blastocyst stage and obtained a singleton live birth were included. Propensity score inverse probability weighting was used to balance baseline maternal characteristics between fresh and FET cycles. RESULTS: Of the 382 women with singleton live births, 124 underwent a fresh blastocyst transfer and 258 underwent a FET. Significantly higher birth weight and length z-scores were observed after FET (P = 0.01 and P = 0.002, respectively) compared with the fresh transfer group. At 12 months of age, the fresh and FET groups showed no significant effect on the weight z-score, but the FET was associated with a higher height z-score (P = 0.001) compared with fresh blastocyst transfer. The comparison between males and females from the same study group showed higher birth weight z-score for males in the FET group (P < 0.001). During the first 12 months, however, males in the FET group showed a slower growth trajectory in terms of weight (P = 0.007). CONCLUSIONS: At 12 months of postnatal life, an increased height and sex-dependent differences in growth trajectories were observed in singletons born after FET compared with those born after fresh embryo transfer.

Levonorgestrel-releasing intrauterine system versus oral medroxyprogesterone acetate in infertile women with endometrial hyperplasia without atypia.

RESEARCH QUESTION: How does use of a levonorgestrel-releasing intrauterine system (LNG-IUS) in infertile women with endometrial hyperplasia without atypia affect endometrial hyperplasia regression and pregnancy rates compared with oral medroxyprogesterone acetate (MPA)? DESIGN: This prospective cohort study included 215 infertile women with an indication for assisted reproductive technology (ART) and a diagnosis of endometrial hyperplasia without atypia. Endometrial hyperplasia was diagnosed by hysteroscopic endometrial biopsy. At the time of first- and second-line treatment, patients were offered therapy with either oral MPA 10 mg daily or LNG-IUS. Follow-up biopsies were scheduled after 90 days' treatment. After endometrial hyperplasia regression, patients were admitted to IVF/intracytoplasmic sperm injection (ICSI) cycles. RESULTS: Baseline characteristics and confounders including age at diagnosis, body mass index and duration of infertility did not differ between LNG-IUS users and control participants and were accounted for using propensity score weighting. Endometrial hyperplasia regression rate at first follow-up was higher in the LNG-IUS group than the oral progestins group (28/28, 100% and 110/187, 58.8%; P < 0.001), while that after second-line treatment was comparable between the two groups (89/91, 97.8% and 122/124, 98.4%; P = 0.22). Clinical pregnancy rate, miscarriage rate and cumulative live birth rate following ART in patients ever receiving LNG-IUS were similar to those of patients receiving only MPA (34% versus 39.5%, 22.6% versus 34.7% and 26.4% versus 25.8%). CONCLUSION: Endometrial hyperplasia regression is greater in women receiving LNG-IUS compared with oral MPA, while live birth rates following ART are comparable between the two groups. The use of LNG-IUS does not jeopardize the chances of pregnancy in women seeking fertility treatment.

The neglected members of the family: non-BRCA mutations in the Fanconi anemia/BRCA pathway and reproduction.

BACKGROUND: BReast CAncer (BRCA) genes are extensively studied in the context of fertility and reproductive aging. BRCA proteins are part of the DNA repair Fanconi anemia (FA)/BRCA pathway, in which more than 20 proteins are implicated. According to which gene is mutated and which interactions are lost owing to the mutation, carriers and patients with monoallelic or biallelic FA/BRCA mutations exhibit very different phenotypes, from overt FA to cancer predisposition or no pathological implications. The effect of the so far neglected non-BRCA FA mutations on fertility also deserves consideration. OBJECTIVE AND RATIONALE: As improved treatments allow a longer life expectancy in patients with biallelic FA mutations and overt FA, infertility is emerging as a predominant feature. We thus reviewed the mechanisms for such a manifestation, as well as whether they also occur in monoallelic carriers of FA non-BRCA mutations. SEARCH METHODS: Electronic databases PUBMED, EMBASE and CENTRAL were searched using the following term: 'fanconi' OR 'FANC' OR 'AND' 'fertility' OR 'pregnancy' OR 'ovarian reserve' OR 'spermatogenesis' OR 'hypogonadism'. All pertinent reports in the English-language literature were retrieved until May 2021 and the reference lists were systematically searched in order to identify any potential additional studies. OUTCOMES: Biallelic FA mutations causing overt FA disease are associated with premature ovarian insufficiency (POI) occurring in the fourth decade in women and with primary non-obstructive azoospermia (NOA) in men. Hypogonadism in FA patients seems mainly associated with a defect in primordial germ cell proliferation in fetal life. In recent small, exploratory whole-exome sequencing studies, biallelic clinically occult mutations in the FA complementation group A (Fanca) and M (Fancm) genes were found in otherwise healthy patients with isolated NOA or POI, and also monoallelic carrier status for a loss-of-function mutation in Fanca has been implicated as a possible cause for POI. In those patients with known monoallelic FA mutations undergoing pre-implantation genetic testing, poor assisted reproduction outcomes are reported. However, the mechanisms underlying the repeated failures and the high miscarriage rates observed are not fully known. WIDER IMPLICATIONS: The so far 'neglected' members of the FA/BRCA family will likely emerge as a relevant focus of investigation in the genetics of reproduction. Several (rather than a single) non-BRCA genes might be implicated. State-of-the-art methods, such as whole-genome/exome sequencing, and further exploratory studies are required to understand the prevalence and mechanisms for occult FA mutations in infertility and recurrent miscarriage.

The Importance of a Multi-Disciplinary Approach to the Endometriotic Patients: The Relationship between Endometriosis and Psychic Vulnerability.

Endometriosis is a chronic inflammatory condition, which is distinguished by the presence of the endometrial-like glands and stroma outside the uterine cavity. Pain and infertility are the most commonly expressed symptoms, occurring in 60% and 40% of cases, respectively. Women with endometriosis, especially those with pelvic pain, also have a greater vulnerability to several psychiatric disorders. There is, in particular, a tendency to contract affective or anxiety disorders as well as panic-agoraphobic and substance use disorders. Endometriosis with pelvic pain, infertility and psychic vulnerability usually leads to disability and a markedly lower quality of life for women of reproductive age. Thus, the burden of endometriosis is not limited to the symptoms and dysfunctions of the disease; it extends to the social, working and emotional spheres, leading to a severe impairment of global functioning. An analysis of scientific literature revealed a close relationship between specific temperamental traits, the expression of several psychiatric symptoms, chronicity of pain, risk of substance use and lower probability of a positive outcome. Endometriosis symptoms and the impact of related psychological consequences, increased vulnerability and the possible onset of psychiatric symptoms may influence coping strategies and weaken resilience, so triggering a vicious cycle leading to a marked deterioration in the quality of life. A multidisciplinary approach consisting of a medical team composed of gynecologists, psychologists, psychiatrists, experts in Dual Disorder, algologists and sexologists, would guarantee the setting of a target and taking the best decision on a personalized treatment plan. That approach would allow the prompt detection of any psychopathological symptoms and improve the endometriosis-related physical symptoms, bringing a healthier quality of life and a greater likelihood of a positive outcome.

Female Reproductive Health and Exposure to Phthalates and Bisphenol A: A Cross Sectional Study.

The xenoestrogenicity of some plasticisers (phthalates and bisphenol A) is documented in the literature and may pose a risk to female reproductive health. The aim of this study was to assess exposure to six phthalates. This was achieved by measuring their respective metabolites (mono-ethylphthalate (MEP); mono-n-butylphthalate (MnBP); mono-n-ottylphthalate (MnOP); and monobenzylphthalate (MBzP)), as well as the sum of two of the diethyl-hexyl phthalate metabolites-(∑DEHP) and bisphenol A (BPA) in a female population with infertility problems, and by conducting a correlation analysis between infertility factors, work activities, and lifestyle habits, in order to formulate a causal hypothesis. A cross-sectional epidemiological study was carried out and women under 43 years of age were recruited from an assisted reproduction technology (ART) center; the sample of 186 women was given a specific questionnaire and a spot urine sample was collected. Phthalate metabolites and urinary BPA were analyzed by HPLC/MS/MS. The results showed significantly higher mean values for MEP in women with recurrent pregnancy loss (RPL) (820.5 ± 1929.5 µg/g of creatinine) and idiopathic infertility (230.0 ± 794.2 µg/g of creatinine) than in women with other infertility factors (76.9 ± 171.8 µg/g of creatinine). Similarly, for MnOP levels, women with idiopathic infertility (2.95 ± 3.44 µg/g of creatinine) showed significantly higher values than women with the other infertility factors taken together (1.35 ± 2.05 µg/g of creatinine). Women with tubal factors of infertility, RPL, and endocrine dysfunctions show higher values of DEHP (p = 0.032). Considering occupations, women working in commerce showed more than twice as much urinary BPA levels (1.10 ± 0.48 µg/g of creatinine) compared to women working in other industries (0.45 ± 0.35 µg/g of creatinine). The presence of significantly higher values of certain phthalates, DEHP in particular, especially in women with RPL and idiopathic infertility, suggests a possible involvement of these compounds as competing factors in reproductive issues. The study of sources of exposure suggested that the working activity in trade, as a casher in particular, represents a major one for BPA (p = 0.015).

Cross Sectional Study on Exposure to BPA and Phthalates and Semen Parameters in Men Attending a Fertility Center.

Among the possible risk factors for male reproduction, exposure to phthalates and alkylphenols is widely documented. This study evaluated the possible association between chemical exposure and the quality of the seminal fluid of 105 subjects in a fertility clinic. The urinary levels of seven phthalate metabolites (monoethylphthalate, MEP; monobenzylphthalate, MBzP; mono n-butylphthalate, MnBP; mono-(2-ethylhexyl) phthalate, MEHP; mono(2-ethyl-5-hydroxyhexyl) phthalate, MEHHP; mono-n-octylphthalate, MnOP; mono-isononylphthalate, MiNP) and bisphenol A (BPA), were analysed by high performance liquid chromatography/tandem mass spectrometry HPLC/MS/MS. The regression analysis showed that the semen volume was positively associated with MnBP, MnOP and BPA levels while was negatively associated with MiNP levels. The sperm concentration had a significant inverse relationship with MEP levels. A negative association was found between the use of plastic containers for food storage (p = 0.037) and semen volume (3.06 vs. 2.30 mL as average values, never vs daily). A significant positive correlation emerged (p < 0.005) between the consumption of canned food and the levels of BPA (2.81 vs. 0.14 µg/g creat as average values, daily vs. never) and between the use of perfumes and levels of MEP (389.86 vs. 48.68 µg/g creat, as average values, daily vs. never). No further statistically significant associations were found, even considering the working activity. Some evidence emerged about the possible link between exposure and seminal fluid quality: further case/control or prospective studies will allow us to confirm this causality hypothesis.