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Journal: Reproductive sciences (Thousand Oaks, Calif.)

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Ovarian cryopreservation followed by autotransplantation is still considered an experimental strategy for fertility preservation (FP) mainly because the success rates are unknown.

Concepts: Fertility, Fertility preservation

27

Objectives:Deep infiltrating endometriosis (DIE) represents the most complex form of endometriosis and its treatment is still challenging. The coexistence of DIE with other appearances of endometriosis stimulates new studies to improve the preoperative diagnosis. Adenomyosis is a clinical form that shares several symptoms with DIE. The present study investigated the possible presence of adenomyosis in a group of women with DIE and its impact on pre- and postoperative symptoms.Materials and Methods:A group of women (n = 121) undergoing laparoscopic treatment for DIE were enrolled. Clinical and ultrasound evaluations were performed as preoperative assessment. The ultrasonographical appearances of DIE and of adenomyosis were recorded by 2-dimensional ultrasound. The following symptoms were considered: dysmenorrhea, dyspareunia, abnormal uterine bleeding, bowel, and urinary symptoms. Pain was evaluated by the visual analog scale system and menstrual bleeding was assessed by the use of the pictorial blood assessment chart. In a subgroup of women (n = 55), a follow-up evaluation (3-6 months after surgery) was done.Results:A relevant number of patients with DIE showed adenomyosis (n = 59; 48.7%); in this group, dysmenorrhea (P = .0019), dyspareunia (P = .0004), and abnormal uterine bleeding (P < .001) were statistically higher than that in the group with only DIE. After surgery, painful symptoms improved in the whole group but remained significantly higher (P < .001) in the group with adenomyosis.Conclusions:Deep infiltrating endometriosis is frequently associated with adenomyosis, significantly affecting pre- and postoperative symptoms and thus influencing the follow-up management.

Concepts: Combined oral contraceptive pill, Menopause, Menstrual cycle, Endometrium, Menstruation, Endometriosis, Adenomyosis, Menorrhagia

26

The etiology of endometriosis remains poorly understood but circulating stem cells may contribute. Telomeres shorten with cell divisions and age. Stem cells attempt to compensate for telomere attrition through the action of telomerase. Since circulating stem cells may contribute to endometriosis, we compared telomere content in lymphocytes of patients with and without endometriosis.Methods:Observational study comparing peripheral lymphocytes telomere content, measured by quantitative polymerase chain reaction, in patients with (n = 86) and without endometriosis (n = 21).Findings:Patients with endometriosis had longer telomeres than that of matched, endometriosis-free controls (telomere to single copy gene ratio [T/S ratio] of 1.62 vs 1.34, respectively, P = .00002). Patients with endometriosis were 8.1-fold more likely to have long telomeres. (odds ratio = 8.1, 95% confidence interval: 1.28-51.57, P = .0264).Interpretation:Longer telomeres could be consistent with a stem cell origin of endometriosis.

Concepts: DNA, Gene expression, Enzyme, Cell division, Stem cell, Chromosome, DNA replication, Reverse transcriptase

26

Myoinositol (MI) and d-chiroinositol (DCI) are 2 stereoisomers and insulin sensitizers. Their physiological ratio differs from tissue to tissue, and they are regulated by an insulin-dependent epimerase whose activity is drastically reduced in conditions of insulin resistance. Based on literature data and on the fact that MI phospholipids are follicle-stimulating hormone (FSH) second messengers, we speculated that patients with polycystic ovary syndrome (PCOS) having hyperinsulinemia, present an enhanced MI to DCI epimerization in the ovary, leading to MI deficiency that impairs FSH signaling, resulting in reduced oocyte quality. In the present study, 20 patients with PCOS and 20 healthy women were enrolled for measurement of MI and DCI levels in their follicular fluid. Follicular fluid samples were taken using a vaginal probe and both MI and DCI were quantified analytically. Results showed that the ratio of MI-DCI dropped from 100:1 in healthy participants to 0.2:1 in patients with PCOS who additionally displayed significantly higher levels of insulin resistance, hyperinsulinemia, and luteinizing hormone. This study is the first one to analyze the misbalance in the MI-DCI ratio in the ovary of patients with PCOS, supporting the concept that maintaining the physiological levels of the 2 stereoisomers is crucial, in restoring the ovarian functionality.

Concepts: Signal transduction, Hormone, Menopause, Endocrinology, Luteinizing hormone, Metformin, Follicle-stimulating hormone, Polycystic ovary syndrome

24

Mitochondrial dysfunction has been suggested as a major cause of age-induced decline in oocyte quality. In the past, donor oocyte cytoplasmic transfer showed some success but was abandoned due to the concerns with heteroplasmy. Recent studies indicated presence of oogonial precursor cells (OPCs) in the human ovary, which could be an autologous source of “healthy mitochondria.” We sought to investigate the clinical efficacy of OPC-derived autologous mitochondrial injection (AMI) to improve oocyte quality in women with multiple in vitro fertilization (IVF) failures.

Concepts: Cell, Reproduction, Eukaryote, Mitochondrion, Mitochondrial DNA, Cytosol, Cytoplasm, In vitro fertilisation

3

The effectiveness of emergency contraception (EC) is usually estimated by comparing the number of observed pregnancies to that of expected pregnancies after unprotected intercourse. Second-generation selective progesterone receptors modulators have been developed and evaluated for EC use. Among these compounds, ulipristal acetate (UPA) has been proven to share the same antiprogestin activity as mifepristone, and as with mifepristone, UPA has been demonstrated to be effective up to 120 hours after unprotected intercourse. The UPA is more effective than levonorgestrel (LNG) in preventing the appearance of clinically evident pregnancies. The LNG delays ovulation only when taken at the beginning of the fertile period; taken later, it is ineffective on ovulation, while it has been proven to impair the subsequent luteal function. The effectiveness of LNG decreases as time elapses and is limited to 72 hours after unprotected intercourse. The UPA maintains consistent effectiveness for 5 days after unprotected intercourse, and this effectiveness is independent on which of these 5 days it is taken. The ability of UPA to delay ovulation decreases progressively as ovulation approaches and is null at the time of the luteinizing hormone (LH) peak: 1 to 2 days before ovulation, UPA behaves as a placebo. The persistent effectiveness of the drug cannot be due to antiovulatory action, as it decreases sharply as LH approaches its peak level. The effectiveness is most likely due to the dramatic endometrial effects of the drug that are produced regardless of when it is taken. These effects are consistently present, as the threshold for altering endometrial morphology is lower than the threshold for altering folliculogenesis.

Concepts: Emergency contraception, Hormonal contraception, Luteinizing hormone, Menstrual cycle, Corpus luteum, Progesterone, Human chorionic gonadotropin, Ovulation

2

Elevated body mass index (BMI) is associated with the incidence, prevalence, and progression of pelvic organ prolapse (POP). This study investigated the effect of peripartum BMI on pelvic floor support 1 year postpartum (PP1y). One hundred eight nulliparous women had their BMI recorded and underwent POP assessments using the Pelvic Organ Prolapse Quantification System at baseline, third trimester (36th to 38th week of pregnancy [G36-38w]), and PP1y. Pelvic organ prolapse was defined as ≥stage II. Women gained on average 1.9 kg between baseline and PP1y. After adjustment, increasing BMI PP1y was associated with increasing anterior wall descent (P < .0001) and higher odds of having POP PP1y (odds ratio: 1.41, 95% confidence interval: 1.01-1.97, P = .045). Trial of labor compared to unlabored cesarean delivery, POP G36-38w, and decreased fetal weight were independently associated with anterior vaginal wall laxity PP1y. Our finding suggests that postpartum BMI influences pelvic floor laxity 1 year after delivery. Postpartum weight reduction may serve as a strategy for POP prevention in some women.

Concepts: Pregnancy, Childbirth, Uterus, Medical statistics, Mass, Obstetrics, Body mass index, Kilogram

1

The association between maternal smoking and preterm birth (PTB) has been known for more than 50 years but the effect of passive smoking is controversial. This retrospective cohort study in Bristol, United Kingdom, examines the effect of environmental tobacco smoke exposure (ETSE) on gestational age at delivery, birth weight, PTB, and being small-for-gestational age (SGA). Environmental tobacco smoke exposure was defined by either self-report or exhaled carbon monoxide (eCO) levels, and exposed women were compared with unexposed controls. Two models were used: The first included all women with adjustment for maternal smoking, and the second considered nonsmokers alone. Both models were further adjusted for maternal age, body mass index, parity, ethnicity, employment status, socioeconomic position, asthma, preeclampsia, and offspring sex. Logistic regression and likelihood ratio tests were used to test for any association between exposure and the binary outcomes (PTB and SGA), while linear regression and F tests were used to test for associations between exposure and the continuous outcomes. There were 13 359 deliveries in 2012 to 2014, with complete data for 5066 and 4793 women in the self-reported and eCO-measured exposure groups, respectively. Self-reported exposure was associated with earlier delivery (-0.19 weeks; 95% confidence interval [CI]: -0.32 to -0.05) and reduced birth weight (-56 g, 95% CI: -97 to -16 g) but no increase in the risk of PTB or SGA. There was no evidence for an association between eCO-measured exposure and any of the outcome measures. This information is important when advising women and their families and adds further support to continued public health efforts to reduce exposure to tobacco smoke.

Concepts: Cohort study, Childbirth, Smoking, Tobacco, Tobacco smoking, Passive smoking, Obstetrics, Likelihood-ratio test

1

This Phase 2 study evaluated the safety and efficacy of elagolix for treating endometriosis-associated pain. A total of 155 women with laparoscopically confirmed endometriosis were randomized to placebo, elagolix 150 mg, or elagolix 250 mg once daily for 12 weeks. Placebo patients were rerandomized to elagolix and elagolix patients continued their dosing assignment for 12 additional weeks; the primary efficacy measure was changed from baseline in the monthly mean numerical rating scale for pain at week 12. Monthly mean (standard error of the mean) reductions were greater with elagolix versus placebo (-1.19 ± 0.18, -1.25 ± 0.18, and -0.88 ± 0.18 for elagolix 150 mg, 250 mg, and placebo, respectively); differences were not statistically significant. Monthly mean dysmenorrhea and nonmenstrual pelvic pain scores were reduced with elagolix, with significant differences for dysmenorrhea at weeks 8 and 12 versus placebo (P < .05). Minimal bone mineral density changes were observed with elagolix treatment. In women with endometriosis-associated pain, elagolix demonstrated an acceptable efficacy and safety profile in this Phase 2 study.

Concepts: Statistics, Density, Statistical significance, Placebo, Arithmetic mean, Acupuncture, Standard deviation, Endometriosis

1

Reproductive tract infection is a major initiator of preterm birth (PTB). The objective of this prospective cohort study of 88 participants was to determine whether PTB correlates with the vaginal microbiome during pregnancy. Total DNA was purified from posterior vaginal fornix swabs during gestation. The 16S ribosomal RNA gene was amplified using polymerase chain reaction primers, followed by chain-termination sequencing. Bacteria were identified by comparing contig consensus sequences with the Ribosomal Database Project. Dichotomous responses were summarized via proportions and continuous variables via means ± standard deviation. Mean Shannon Diversity index differed by Welch t test (P = .00016) between caucasians with PTB and term gestation. Species diversity was greatest among African Americans (P = .0045). Change in microbiome/Lactobacillus content and presence of putative novel/noxious bacteria did not correlate with PTB. We conclude that uncultured vaginal bacteria play an important role in PTB and race/ethnicity and sampling location are important determinants of the vaginal microbiome.

Concepts: DNA, Gene, Childbirth, Molecular biology, RNA, Ribosomal RNA, Ribosome, Reproductive system