Varicocele recurrence is one of the most common complications associated with varicocele repair. A systematic review was performed to evaluate varicocele recurrence rates, anatomic causes of recurrence, and methods of management of recurrent varicoceles. The PubMed database was evaluated using keywords "recurrent" and "varicocele" as well as MESH criteria "recurrent" and "varicocele." Articles were not included that were not in English, represented single case reports, focused solely on subclinical varicocele, or focused solely on a pediatric population (age <18). Rates of recurrence vary with the technique of varicocele repair from 0% to 35%. Anatomy of recurrence can be defined by venography. Management of varicocele recurrence can be surgical or via embolization.
Hua R et al., 2016·Nan fang yi ke da xue xue bao = Journal of Southern Medical University
To investigate the associations of occupational, educational and residential factors with the outcomes of in vitro fertilization -embryo transfer (IVF-ET). A retrospective analysis was conducted among 3998 patients undergoing the first treatment with IVF-ET and 3064 perinatal infants in our center between January, 2010 and June, 2014. The relation of the patients' occupation, educational background, and residence registry with IVF-ET outcomes was analyzed. The risk of abortion in the first trimester was significantly higher in female patients engaged in agriculture (OR=4.319, P=0.047). Occupation and educational background of the patients and their spouse were related with the incidence of ectopic pregnancy following IVF-ET. The total incidence rate of perinatal birth defects was 2.1% in this cohort, and was the highest in Shenzhen (5.5%) but this difference was not statistically significant (P>0.05). The patients' occupation and educational background are related with the outcomes of IVF-ET, suggesting the importance of health education and prenatal examination.
NaProTECHNOLOGYHuman Dignity in Infertility TreatmentAssisted Reproduction CritiqueNaProTECHNOLOGY vs ART
Open Access
The article raises the issue of today’s application of assisted (artificial) reproduction methods, which are incom-patible with human dignity. The authors articulate the principles of human dignity, which are formulated as an evaluation tool of criteria and them revealing system of indicators in the assessed object. The article compares Naprotechnology as a contemporary holistic method of diagnosis and treatment of infertility, which comprises therapeutic, surgical and fertility awareness method, with methods of assisted reproduction and identifies their medical and ethical differences. The project of the Assisted Reproduction Law of the Republic of Lithuania is evaluated in the aspect of human dignity as well.
Annual report (Jahrbuch) of the Deutsches IVF-Register (DIR) for treatment year 2015. DIR is the German national IVF/ICSI registry, founded 1982 — the oldest continuously operating ART registry. Voluntary professional-society database with high de-facto coverage of German fertility centres. Reports cycles, transfers, pregnancies and clinical outcomes by treatment type (IVF, ICSI, frozen embryo transfer, donor). German-language registry document. Used as a Phase B historical-archive source for the ART Registry Comparison study (cross-registry classification by reporting completeness on 7 framework dimensions).
Conduct an economic evaluation based on best currently available evidence comparing alternative treatments levonorgestrel-releasing intrauterine system, depot-medroxyprogesterone acetate, combined oral contraceptive pill (COCP) and 'no treatment' to prevent recurrence of endometriosis after conservative surgery in primary care, and to inform the design of a planned trial-based economic evaluation. We developed a state transition (Markov) model with a 36-month follow-up. The model structure was informed by a pragmatic review and clinical experts. The economic evaluation adopted a UK National Health Service perspective and was based on an outcome of incremental cost per quality-adjusted life year (QALY). As available data were limited, intentionally wide distributions were assigned around model inputs, and the average costs and outcome of the probabilistic sensitivity analyses were reported. On average, all strategies were more expensive and generated fewer QALYs compared to no treatment. However, uncertainty attributing to the transition probabilities affected the results. Inputs relating to effectiveness, changes in treatment and the time at which the change is made were the main causes of uncertainty, illustrating areas where robust and specific data collection is required. There is currently no evidence to support any treatment being recommended to prevent the recurrence of endometriosis following conservative surgery. The study highlights the importance of developing decision models at the outset of a trial to identify data requirements to conduct a robust post-trial analysis.
Sparic R et al., 2016·International journal of fertility & sterility
Myomas are the most common benign tumors of the genital organs in women of childbearing age, causing significant morbidity and impairing their quality of life. In our investigation, we have reviewed the epidemiological data related to the development of myomas in order to homogenize the current data. Therefore, a MEDLINE and PubMed search, for the years 1990-2013, was conducted using a combination of keywords, such as "myoma," "leiomyoma," "fibroids," "myomectomy," "lifestyle," "cigarette," "alcohol," "vitamins," "diet," and "hysterectomy". Randomized controlled studies were selected based upon the authors' estimation. Peer-reviewed articles examining myomas were sorted by their relevance and included in this research. Additional articles were also identified from the references of the retrieved papers and included according to authors' estimation. Many epidemiologic factors are linked to the development of myomas; however, many are not yet fully understood. These factors include age, race, heritage, reproductive factors, sex hormones, obesity, lifestyle (diet, caffeine and alcohol consumption, smoking, physical activity and stress), environmental and other influences, such as hypertension and infection. Some of the epidemiological data is conflicting. Thus, more research is needed to understand all the risk factors that contribute to myoma formation and how they exactly influence their onset and growth.
Khatiwada S et al., 2016·Clinical diabetes and endocrinology
A growing body of evidence suggests that metabolic syndrome is associated with endocrine disorders including thyroid dysfunction. Thyroid dysfunction in metabolic syndrome patients may further add to cardiovascular disease risk thereby increasing mortality. This study was done to assess thyroid function in metabolic syndrome patients and evaluate its relationship with the components of metabolic syndrome. A cross sectional study was carried out among 169 metabolic syndrome patients at B P Koirala Institute of Health Sciences, Dharan, Nepal. Anthropometric measurements (height, weight, waist circumference) and blood pressure were taken. Fasting blood samples were analysed to measure glucose, triglyceride, high density lipoprotein (HDL) cholesterol and thyroid hormones (triiodothyronine, thyroxine and thyroid stimulating hormone). Thyroid dysfunction was seen in 31.9 % (n = 54) metabolic syndrome patients. Subclinical hypothyroidism (26.6 %) was the major thyroid dysfunction followed by overt hypothyroidism (3.5 %) and subclinical hyperthyroidism (1.7 %). Thyroid dysfunction was much common in females (39.7 %, n = 29) than males (26 %, n = 25) but not statistically significant (p = 0.068). The relative risk of having thyroid dysfunction in females was 1.525 (CI: 0.983-2.368) as compared to males. Significant differences (p = 0.001) were observed in waist circumference between patients with and without thyroid dysfunction and HDL cholesterol which had significant negative correlation with thyroid stimulating hormone. Thyroid dysfunction, particularly subclinical hypothyroidism is common among metabolic syndrome patients, and is associated with some components of metabolic syndrome (waist circumference and HDL cholesterol).
Hapangama DK et al., 2016·Women's health (London, England)
Heavy menstrual bleeding (HMB) is a common gynecological complaint with multiple etiologies and diverse pathophysiological origins. This review discusses HMB with reference to the recently proposed PALM-COEIN classification system for abnormal uterine bleeding, initially describing the endometrial events in normal menstruation followed by discussion of the perturbations of normal endometrial shedding that can result in HMB. Our present understanding of the mechanisms of menstrual bleeding as well as many of the pathological aberrations of HMB is incomplete. Further research into the pathophysiology of HMB is urgently needed, as clear knowledge of the mechanisms of this disorder will provide new therapeutic targets to formulate more effective treatments.
NaProTECHNOLOGYPhilippinesFinancial ConstraintsDeveloping Countries
Flores R, 2016·Scholars Academic Journal of Biosciences
The latest retrievable data about infertility in the Philippines was made available to the public by Merck Serono, a private pharmaceutical company who commissioned the survey in 2011. The survey was conducted by Synovate in 100 participating households in the Philippines, particularly in key cities located in Luzon, Visayas and Mindanao. The survey results revealed that one out of ten Filipino couples are suffering from infertility. And these couples are not seeking treatment (1) financial constraints; (2) time constraints; and (3) the patient’s belief. Of all these, financial constraints, at 86%, is the primary reason why infertile couples are not seeking treatment. In addition to this data, the Chief of The Medical City’s Reproductive Medicine, Infertility and Gynecologic Endoscopy, Dr. Marc Anthony Ancheta, further reveals that “some 35 to 40% of a couple’s inablity to conceive a child are due to female factors; while the other 35 to 40% could be attributed to male factors.” While male factor infertility is also deserving of proper attention, it is the female factor infertility that should receive greater attention and focus in terms of treatment. Why? Because, primarily, the female’s reproductive cycle is very complex and would need months and/or years to partially identify the underlying reason/s of infertility; and second, the female’s ability to conceive naturally will fall by 50% when she reached the age of 35. Therefore, there should be urgency in treating female factor infertility in an efficient, ethical and affordable way. And these conditions can be achieved by the use of NaPro Technology.
Ethics/PhilosophyPrinciple of Double EffectIntended vs Foreseen ConsequencesPregnancy Intervention Decisions
- A pregnant woman is diagnosed with uterine cancer. Is it permissible to operate to remove the cancer, even though doing so will result in the loss of the baby?
- A dying man is in extreme pain. Is it permissible to administer large doses of morphine to reduce the pain, even though doing so will shorten the amount of time the man has left to live?
- A country has been attacked by another. Is it morally permissible for the country that has been attacked to respond by, among other things, bombing its attacker’s industrial centers, even though doing so will also bring about the deaths of some civilian workers?
- A pregnant woman is diagnosed with uterine cancer. Is it permissible to operate to remove the cancer, even though doing so will result in the loss of the baby? Supporters of the principle of double effect will argue that it is permissible to remove the cancerous uterus (thus also terminating the pregnancy) if this is the only way to stop the spread of the cancer and if the physician does not intend to end the pregnancy, only to remove the cancer. The good effect (removal of the cancer) does not follow from the bad effect (termination of the pregnancy).
- A dying man is in extreme pain. Is it permissible to administer large doses of morphine to reduce the pain, even though doing so will shorten the amount of time the man has left to live? Again, defenders of the principle of double effect will argue that, since the genuine intent is only to relieve the pain and since there is no other way to accomplish this goal, large doses of pain killers may be permitted even though they will hasten the inevitable end of the patient's life.
- A country has been attacked by another. Is it morally permissible for the country that has been attacked to respond by, among other things, bombing its attacker’s industrial centers, even though doing so will also bring about the deaths of some civilian workers? The principle of double effect has been a cornerstone of the wartime policy of many countries, including the United States. Indeed, long range strategic bombers (such as the B-52) are essentially weapons for the mass destruction of civilian populations. Both the atomic bombs dropped on Japan were dropped on civilian centers.
The principle of double effect finds its natural home in deontological, non-consequentialist moral theories, since it turns very specifically on the intention of the moral agent.
Utilitarianism and other consequentialist doctrines give little or no weight to the agent’s intentions, and as a result the principle of double effect makes little sense within such theories.
We will see a similar issue arise when we discuss the difference between killing and letting die, a distinction that is much more meaningful within deontological theories than consequentialist ones.
Typically, for an act to qualify as morally permissible under the principle of the double effect, a number - The act must be morally good or at least morally neutral;
- The agent must intend only the good effect, nor the bad effect;
- The good effect cannot be the causal result of the bad effect;
- There must be a proportionately serious reason for permitting the evil effect;
- There must not be any other, less morally troubling way of accomplishing the good effect.
To determine whether there are any increases in pregnancy-related complications and adverse pregnancy outcomes in singleton pregnancies after assisted reproductive technology (ART) compared with those conceived naturally. Meta-analysis. University-affiliated teaching hospital. PATIENT(S): Singleton pregnancies conceived with ART and naturally. INTERVENTION(S): PubMed, Google Scholar, Cochrane Libraries and Chinese database were searched through March 2015 to identify studies that met pre-stated inclusion criteria. Either a fixed- or a random-effects model was used to calculate the overall combined risk estimates. Subgroup analysis was performed to explore potential heterogeneity moderators. MAIN OUTCOME MEASURE(S): Pregnancy-related complications and adverse pregnancy outcomes. RESULT(S): Fifty cohort studies comprising 161,370 ART and 2,280,241 spontaneously conceived singleton pregnancies were identified. The ART singleton pregnancies had a significantly increased risk of pregnancy-induced hypertension (relative risk [RR] 1.30, 95% confidence interval [CI] 1.04-1.62; I(2) = 79%), gestational diabetes mellitus (RR 1.31, 95% CI 1.13-1.53; I(2) = 6%), placenta previa (RR 3.71, 95% CI 2.67-5.16; I(2) = 72%), placental abruption (RR 1.83, 95% CI 1.49-2.24; I(2) = 22%), antepartum hemorrhage (RR 2.11, 95% CI 1.86-2.38; I(2) = 47%), postpartum hemorrhage (RR 1.29, 95% CI 1.06-1.57; I(2) = 65%), polyhydramnios (RR 1.74, 95% CI 1.24-2.45; I(2) = 0%), oligohydramnios (RR 2.14, 95% CI 1.53-3.01; I(2) = 0%), cesarean sections (RR 1.58, 95% CI 1.48-1.70; I(2) = 92%), preterm birth (RR 1.71, 95% CI 1.59-1.83; I(2)=80%), very preterm birth (RR 2.12, 95% CI 1.73-2.59; I(2) = 90%), low birth weight (RR 1.61, 95% CI 1.49-1.75; I(2) = 80%), very low birth weight (RR 2.12, 95% CI 1.84-2.43; I(2) = 67%), small for gestational age (RR 1.35, 95% CI 1.20-1.52; I(2) = 82%), perinatal mortality (RR 1.64, 95% CI 1.41-1.90; I(2)=45%), and congenital malformation (RR 1.37, 95% CI 1.29-1.45; I(2)=41%). Relevant heterogeneity moderators have been identified by subgroup analysis. Sensitivity analysis yielded consistent results. No evidence of publication bias was observed. CONCLUSION(S): The ART singleton pregnancies are associated with higher risks of adverse obstetric outcomes. Obstetricians should manage these pregnancies as high risk.
Dyer S et al., 2016·Human reproduction (Oxford, England)
20. International Committee for Monitoring Assisted Reproductive Assisted Reproductive Technology 2008, 2009 and 2010. Dyer S(1), Chambers GM(2), de Mouzon J(3), Nygren KG(4), Zegers-Hochschild F(5), Mansour R(6), Ishihara O(7), Banker M(8), Adamson GD(9). (1)Department of Obstetrics & Gynaecology, Groote Schuur Hospital and Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa silke.dyer@uct.ac.za. (2)National Perinatal Epidemiology and Statistics Unit, University of New South Wales, Sydney, Australia. (3)Institut National de la Santé et de la Recherche Médicale Service de Gynécologie Obstétrique II et de Médecine de la Reproduction, Groupe Hospitalier Cochin-Saint Vincet de Paul, Paris, France. (4)Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. (5)Clinica las Condes and Program of Ethics and Public Policies in Human Reproduction, University Diego Portales, Santiago, Chile. (6)Egyptian IVF-ET Center, Cairo, Egypt. (7)Department of Obstetrics and Gynaecology, Saitama Medical University, Moroyama, Japan. (8)Nova IVI Fertility, Chennai, India. (9)Palo Alto Medical Foundation Fertility Physicians of North California, San Jose, CA, USA. Comment in Hum Reprod. 2016 Jul;31(7):1381-2. 10.1093/humrep/dew092. What were utilization, outcomes and practices in assisted reproductive technology (ART) globally in 2008, 2009 and 2010? Global utilization and effectiveness remained relatively constant despite marked variations among countries, while the rate of single and frozen embryo transfers (FETs) increased with a concomitant slight reduction in multiple birth rates. ART is widely practised in all regions of the world. Monitoring utilization, an approximation of availability and access, as well as effectiveness and safety is an important component of universal access to reproductive health. STUDY DESIGN, SIZE, This is a retrospective, cross-sectional survey on utilization, effectiveness and safety of ART procedures performed globally from 2008 to 2010. PARTICIPANTS, SETTING, Between 58 and 61 countries submitted data from a total of nearly 2500 ART clinics each year. Aggregate country data were processed and analyzed based on forms and methods developed by the International Committee for Monitoring Assisted Reproductive Technologies (ICMART). Results are presented at country, regional and global level. MAIN For the years 2008, 2009 and 2010, >4 461 309 ART cycles were initiated, resulting in an estimated 1 144 858 babies born. The number of aspirations increased by 6.4% between 2008 and 2010, while FET cycles increased by 27.6%. Globally, ART utilization remained relatively constant at 436 cycles/million in 2008 and 474 cycles/million population in 2010, but with a wide country range of 8-4775 cycles/million population. ICSI remained constant at around 66% of non-donor aspiration cycles. The IVF/ICSI combined delivery rate (DR) per fresh aspiration was 19.8% in 2008; 19.7% in 2009 and 20.0% in 2010, with corresponding DRs for FET of 18.8, 19.7 and 20.7%. In fresh non-donor cycles, single embryo transfer increased from 25.7% in 2008 to 30.0% in 2010, while the average number of embryos transferred fell from 2.1 to 1.9, again with wide regional variation. The rates of twin deliveries following fresh non-donor transfers were, in 2008, 2009 and 2010, 21.8, 20.5 and 20.4%, respectively, with a corresponding triplet rate of 1.3, 1.0 and 1.1%. Fresh IVF and ICSI carried a perinatal mortality rate per 1000 births of 22.8 (2008), 19.2 (2009) and 21.0 (2010), compared with 15.1, 12.8 and 14.6/1000 births following FET in the same periods of observation. The proportion of women aged 40 years or older undergoing non-donor ART increased from 20.8 to 23.2% from 2008 to 2010. LIMITATIONS, The data presented are reliant on the quality and completeness of data submitted by individual countries. This report covers approximately two-thirds of the world ART activity. The ICMART World Reports provide the most comprehensive global statistical census and review of ART utilization, effectiveness, safety and quality. While ART treatment continues to increase globally, the wide disparities in access to treatment and embryo transfer practices warrant attention by clinicians and policy makers. The authors declare no conflict of interest and no specific support from any organizations in relation to this manuscript. ICMART acknowledges financial support from American Society for Reproductive Medicine; European Society for Human Reproduction and Embryology; Fertility Society of Australia; Japan Society for Reproductive Medicine; Japan Society of Fertilization and Implantation; Red Latinoamericana de Reproduccion Asistida; Society for Assisted Re
As the HIV/AIDS epidemic continues to spread in Africa and Asia, use of the injectable contraceptive steroid DMPA is widespread and has been increasing. Since studies dating back to 1992 have suggested that DMPA may increase the transmission of HIV to women, we endeavored to determine if the extant epidemiological and biological evidence is sufficient to conclude that DMPA use constitutes a definite hazard to women's health. We searched contraceptives or contraception AND HIV and searched bibliographies of articles thus identified. We included in the meta-analysis all studies examining the association between use of DMPA (or injectable contraceptives comprising mostly DMPA) and the presence (cross-sectional studies, n = 8) or acquisition (longitudinal studies, n = 16) of HIV+ status in women, using a random effects models to estimate odds ratios (ORs; cross-sectional studies) and hazard ratios (HRs; longitudinal studies). Studies were excluded if the comparison group included women using any form of steroidal contraception. Statistically significant positive associations between DMPA use and HIV positivity were observed both in cross-sectional (OR = 1.41, 95% CI 1.15 - 1.73) and longitudinal studies (HR = 1.49, 95% CI 1.28 - 1.73). The biological plausibility of increased vulnerability to HIV infection due to progestational action (via thinning of the vaginal epithelial barrier and immunosuppression) as well as glucocorticoid agonistic immunosuppression, are discussed. The epidemiological and biological evidence now make a compelling case that DMPA adds significantly to the risk of male-to-female HIV transmission.
Progesterone support in pregnancy has been in use for over 60 years, having received its start in the 1940s. Its initial use was in patients who had habitual spontaneous abortion caused by luteal phase deficiency. More recently, the administration of progesterone later in pregnancy has been considered to be justified because of an observed decrease in circulating progesterone with the onset of labor, an association of premature labor with decreased progesterone concentrations, and the observation that progesterone has a tocolytic effect. A considerable boost to the use of progestational agents to reduce preterm delivery was received with the publication of two papers which showed a significant reduction in preterm delivery rates with the prophylactic administration of either progesterone or 17-a hydroxyprogesterone caproate. Recently it has been shown, however, that its use is not universal. This may be related to the significant late sequelae that were documented following the in utero exposure of the fetus to the potent steroid diethylstilbestrol (DES) and that this bad experience cast “a long shadow,” In spite of this, the use of progesterone, at least in early pregnancy, is widespread in the various artificial reproductive programs and is growing in its use as an agent to reduce prematurity. Over the years, there has been an extraordinary amount of confusion related to the use of progesterone support in pregnancy. The Food & Drug Administration (FDA) created some of this confusion. In various labeling of progesterone products by the FDA, one of the contraindications to the use of oral progesterone is listed as “known or suspected pregnancy.” And, yet, no such contraindication is identified for the use of progesterone gel. In fact, progesterone gel is indicated for progesterone supplementation or replacement as a part of an assisted reproductive technology (ART) treatment program for infertile women with a progesterone deficiency. To make this even more confusing, oral progesterone, while it was contraindicated in “known or suspected pregnancy,” its official labeling stated that it “should be used during pregnancy only if indicated (see contraindications).” Also, up until very recently, there was a dire “warning” contained in the labeling for USP progesterone injection in sesame seed oil regarding an increased possibility of birth defects. An analysis of the fetal safety of isomolecular progesterone (Pregn-4-ene-3,20-dione) administration during the course of 1,310 pregnancies over a 35-year period of time (1979-2014) was undertaken to address this confusion.
Santamaria A et al., 2015·J Matern Fetal Neonatal Med
To evaluate whether myo-inositol supplementation may reduce gestational diabetes mellitus (GDM) rate in overweight women. In an open-label, randomized trial, myo-inositol (2 g plus 200 μg folic acid twice a day) or placebo (200 μg folic acid twice a day) was administered from the first trimester to delivery in pregnant overweight non-obese women (pre-pregnancy body mass index ≥ 25 and < 30 kg/m(2)). The primary outcome was the incidence of GDM. From January 2012 to December 2014, 220 pregnant women were randomized at two Italian University hospitals, 110 to myo-inositol and 110 to placebo. The incidence of GDM was significantly lower in the myo-inositol group compared to the placebo group (11.6% versus 27.4%, respectively, p = 0.004). Myo-inositol treatment was associated with a 67% risk reduction of developing GDM (OR 0.33; 95% CI 0.15-0.70). Myo-inositol supplementation, administered since early pregnancy, reduces GDM incidence in overweight non-obese women.
Perimenopause/MenopauseDietary PatternsDiet and Glucose MetabolismInsulin Resistance and Bone
We hypothesized that diet would have direct effects on glucose metabolism with direct and indirect effects on bone metabolism in a cohort of Canadian adults. We assessed dietary patterns (Prudent [fruit, vegetables, whole grains, fish, and legumes] and Western [soft drinks, potato chips, French fries, meats, and desserts]) from a semiquantitative food frequency questionnaire. We used fasting blood samples to measure glucose, insulin, homeostatic model assessment insulin resistance (HOMA-IR), 25-hydroxyvitamin D (25OHD), parathyroid hormone, bone-specific alkaline phosphatase (a bone formation marker), and serum C-terminal telopeptide (CTX; a bone resorption marker). We used multivariate regression models adjusted for confounders and including/excluding body mass index. In a secondary analysis, we examined relationships through structural equations models. The Prudent diet was associated with favorable effects on glucose metabolism (lower insulin and HOMA-IR) and bone metabolism (lower CTX in women; higher 25OHD and lower parathyroid hormone in men). The Western diet was associated with deleterious effects on glucose metabolism (higher glucose, insulin, and HOMA-IR) and bone metabolism (higher bone-specific alkaline phosphatase and lower 25OHD in women; higher CTX in men). Body mass index adjustment moved point estimates toward the null, indicating partial mediation. The structural equation model confirmed the hypothesized linkage with strong effects of Prudent and Western diet on metabolic risk, and both direct and indirect effects of a Prudent diet on bone turnover. In summary, a Prudent diet was associated with lower metabolic risk with both primary and mediated effects on bone turnover, suggesting that it is a potential target for reducing fracture risk.
Comment in BMJ. 2015 Dec 23;351:h6913. 10.1136/bmj.h6913. JAMA. 2015 Dec 22-29;314(24):2627-9. 10.1001/jama.2015.17297. The likelihood of achieving a live birth with repeat in vitro fertilization (IVF) is unclear, yet treatment is commonly limited to 3 or 4 embryo transfers. To determine the live-birth rate per initiated ovarian stimulation IVF cycle and with repeated cycles. DESIGN, SETTING, Prospective study of 156,947 UK women who received 257,398 IVF ovarian stimulation cycles between 2003 and 2010 and were followed up until June 2012. In vitro fertilization, with a cycle defined as an episode of ovarian stimulation and all subsequent separate fresh and frozen embryo transfers. Live-birth rate per IVF cycle and the cumulative live-birth rates across all cycles in all women and by age and treatment type. Optimal, prognosis-adjusted, and conservative cumulative live-birth rates were estimated, reflecting 0%, 30%, and 100%, respectively, of women who discontinued due to poor prognosis and having a live-birth rate of 0 had they continued. Among the 156,947 women, the median age at start of treatment was 35 years (interquartile range, 32-38; range, 18-55), and the median duration of infertility for all 257,398 cycles was 4 years (interquartile range, 2-6; range, <1-29). In all women, the live-birth rate for the first cycle was 29.5% (95% CI, 29.3%-29.7%). This remained above 20% up to and including the fourth cycle. The cumulative prognosis-adjusted live-birth rate across all cycles continued to increase up to the ninth cycle, with 65.3% (95% CI, 64.8%-65.8%) of women achieving a live birth by the sixth cycle. In women younger than 40 years using their own oocytes, the live-birth rate for the first cycle was 32.3% (95% CI, 32.0%-32.5%) and remained above 20% up to and including the fourth cycle. Six cycles achieved a cumulative prognosis-adjusted live-birth rate of 68.4% (95% CI, 67.8%-68.9%). For women aged 40 to 42 years, the live-birth rate for the first cycle was 12.3% (95% CI, 11.8%-12.8%), with 6 cycles achieving a cumulative prognosis-adjusted live-birth rate of 31.5% (95% CI, 29.7%-33.3%). For women older than 42 years, all rates within each cycle were less than 4%. No age differential was observed among women using donor oocytes. Rates were lower for women with untreated male partner-related infertility compared with those with any other cause, but treatment with either intracytoplasmic sperm injection or sperm donation removed this difference. Among women in the United Kingdom undergoing IVF, the cumulative prognosis-adjusted live-birth rate after 6 cycles was 65.3%, with variations by age and treatment type. These findings support the efficacy of extending the number of IVF cycles beyond 3 or 4.
Fertility AwarenessUrinary Hormone MonitoringBBT and Cervical Mucus ValidationPregnanediol Glucuronide Threshold
Do the basal body temperature (BBT) shift and the cervical mucus markers for the beginning of the post-ovulatory infertile phase (POIP) of a menstrual cycle agree with the corresponding urinary pregnanediol glucuronide (PdG) threshold value? Perfect agreement between the cervical mucus markers and BBT shift and the hormonal definition of the start of post-ovulatory infertility occurred for only 7-17% of the cycles. The PdG threshold of 7.0 µmol/24 h is an objective and accurate marker for the beginning of the POIP. The rise in serum progesterone also produces the BBT shift and changes in cervical mucus which determine the mucus peak. Serum progesterone and urinary PdG are closely correlated when variations in urine volume are taken into account. STUDY DESIGN, SIZE, Individual menstrual cycle profiles of urinary PdG excretion rates for 91 fertile cycles from normally cycling women were analysed to identify the day of the beginning of the POIP. These days were compared with those determined by the day of the BBT shift +2 days, the day of the mucus peak +4 days and the later of these two indicators. The study lasted 3 years. PARTICIPANTS/MATERIALS, SETTING, A total of 62 women with normal menstrual cycles were Palmerston North, New Zealand; Sydney, Australia and Santiago, Chile. The cycles were displayed individually in a proprietary database program which recorded the PdG excretion rates, the BBT shift day and the cervical mucus peak day. A group of 15 women from a separate Chilean study had PdG urinary data measured as well as their day of ovulation determined by ultrasound. MAIN The BBT and cervical mucus markers differed significantly in their identification of the beginning of the POIP when compared with the PdG excretion rate of 7.0 µmol/24 h. The observation that the BBT shift day and the mucus peak day could be identified even though the PdG excretion rates were still at baseline levels in some cycles could lead to an unexpected pregnancy for women using these natural family planning (NFP) indicators. LIMITATIONS, The study consisted only of fertile cycles from women with regular cycles of 20-40 days duration. All the women were intending to avoid a pregnancy during the study, thus the limits of the fertile window were not tested. The NFP signals occurring earlier than the PdG threshold day could lead to an unexpected pregnancy. The signals occurring on the same day or later than the PdG threshold would not lead to unexpected pregnancies, but would require extra abstinence that could lead to non-compliance with the NFP method. A possible improvement in reliability of NFP methods is suggested. This study (project #90905) was funded by the NDP/UNFPA/UNICEF/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP). D.G.C. currently works for a diagnostic development company, Science Haven Ltd. The other authors have nothing to declare.
Contraception/ComparisonBreast Cancer RiskHormone-Releasing IUD SafetyValidation
Main aim was to estimate the association between use of exogenous hormones and breast cancer (BC) risk in a large population-based survey, and to assess the representativeness and overall validity of the data. The survey 'Women's Health and Use of Hormones' was conducted in Finland in 2009, including 7,000 BC cases and 20,000 matched population controls. Conditional logistic regression was used to estimate odds ratios and their 95 % confidence interval. For validation, exposure prevalences were compared with population data from Statistics Finland and two large population-based surveys. We found positive associations with BC risk and exclusive use of hormone-releasing intrauterine device (HR IUD) in postmenopausal women (1.48, 95 % CI 1.10-1.99), when compared to never-users of any hormonal contraceptive and considering only prediagnostic use in cases. Regarding use of other hormonal contraceptives (HC), a positive association between long HC use (≥2 years) and BC was observed in both groups, OR being 1.37 (95 % CI 1.12-1.68) for premenopausal and 1.11 (95 % CI 1.03-1.20) for postmenopausal women, when compared to never-users of other HC. Observed association between HR IUD use and risk of BC in postmenopausal women is worrying and deserves further attention. Selection bias seemed not to explain this result. Considering the increasing popularity of HR IUD use in, e.g., USA, impact of possible adverse effects in public health could be significant.
Casein-free, gluten-free diets have been reported to mitigate some of the and behavioral traits associated with autism, but the mechanism for this palliative effect has not been elucidated. We
recently showed that the opioid peptide beta-casomorphin-7, derived from bovine (bBCM7) milk, uptake, lowers levels of the antioxidant glutathione (GSH) and decreases the methyl (SAM) in both Caco-2 human GI epithelial cells and SH-SY5Y human neuroblastoma cells. can also release a similar peptide (hBCM-7), the bBCM7 and hBCM-7 vary greatly in potency; as the bBCM-7 potent and similar to morphine in it's effects. Since SAM is required for DNA methylation, investigate the epigenetic effects of these food-derived opioid peptides. In the current to characterize functional pathways and key genes responding to DNA methylation peptides. SH-SY5Y neuroblastoma cells were treated with 1 μM hBCM7 and bBCM7 after 4 h with or without treatment. Transcriptional changes were assessed using a methylation status was analyzed at 450,000 CpG sites. Functional implications from both Ingenuity Pathway Analysis 4.0 and KEGG pathway analysis was performed to identify biological transcripts that were significantly altered at DNA methylation or transcriptional levels (p < 0.05, FDR <0.1). Here we show that hBCM7 and bBCM7, as well as morphine, cause epigenetic pathways related to gastrointestinal disease and inflammation. These epigenetic consequences potency order as opiate inhibition of cysteine uptake insofar as hBCM7 was less potent than bBCM7, potent than morphine. Our findings indicate that epigenetic effects of milk-derived opiate dysfunction and inflammation in sensitive individuals. While the current study was performed using SH-SY5Y
neuronal cellular models, similar actions on other cells types might combine to cause symptoms of intolerance. actions may provide a potential contributing mechanism for the beneficial effects of a casein-free gastrointestinal symptoms in neurological conditions including autism and other conditions. Lastly, contributes to the evolving awareness of a “gut-brain connection”.
Epigenetics, Gluten free casein free diet, Autism, Glutathione, Gastrointestinal, Inflammation
Adverse health outcomes related to exposure to endocrine disrupting chemicals, including increased incidences of coronary heart disease, prostate and testicular cancers, and congenital disabilities, have been reported in firefighters or their offspring. We, therefore, measured the estrogenic and antiestrogenic activity of extracts of used firefighter gear to assess exposure to these agents. Extracts and known chemical contaminants were examined for estrogenicity and antiestrogenicity in yeast cells expressing the estrogen receptor. Most extracts of used gear and phthalate diesters detectable on this gear displayed strong antiestrogenic effects. Notably, new glove and hood extracts showed significant estrogenic activity. Overall, our data suggest that firefighters are exposed to both estrogenic and antiestrogenic agents, possibly phthalates that may lead to health risks observed in this occupation as a result of perturbation of hormone homeostasis.
Traditionally, IVF success rates have been reported in terms of live birth per fresh cycle or embryo transfer. With the increasing use of embryo freezing and thawing it is essential that we report not only outcomes following fresh but also those after frozen embryo transfer as a complete measure of success of an IVF treatment. Most people agree that an individual's chance of having a baby following fresh and frozen embryo transfer should be described as cumulative live birth rate. However, views on the most appropriate parameters required to calculate such an outcome have been inconsistent. There is an additional dimension - time for all frozen embryos to be used up by a couple, which can influence the outcome. Given that cumulative live birth rate is generally perceived to be the preferred reporting system in IVF, it is time to have an international consensus on how this statistic is calculated, reported and interpreted by stakeholders across the world.
Daily JW et al., 2015·Pain medicine (Malden, Mass.)
There has been no attempt to date to synthesize the available evidence for the efficacy of ginger for treating primary dysmenorrhea. This systematic review evaluates the current evidence for the effectiveness of ginger for treating primary dysmenorrhea. Literature searches were conducted using 12 electronic databases including PubMed, EMBASE, Cochrane Library, Korean databases, Chinese medical databases, and Indian scientific database. "ginger" or "Zingiber officinale" and "dysmenorrhea" and "pain." Studies using ginger as a treatment of primary dysmenorrhea were considered for inclusion. The major outcome of primary dysmenorrhea was assessed using a pain visual analogue score (PVAS). Initial searches yielded 29 articles. Of these original results, seven met specific selection criteria. Four of the RCTs compared the therapeutic efficacy of ginger with a placebo during the first 3-4 days of the menstrual cycle and were included in the meta analysis. The meta-analysis of these data showed a significant effect of ginger in reducing PVAS in subjects having primary dysmenorrhea (risk ratio, -1.85; 95% CI of -2.87, -0.84, P = 0.0003). Six RCTs out of 7 exhibited low to moderate of risk of bias. Collectively these RCTs provide suggestive evidence for the effectiveness of 750-2000 mg ginger powder during the first 3-4 days of menstrual cycle for primary dysmenorrhea.
Progesterone is essential for the maintenance of pregnancy. However, whether progesterone supplementation in the first trimester of pregnancy would increase the rate of live births among women with a history of unexplained recurrent miscarriages is uncertain. We conducted a multicenter, double-blind, placebo-controlled, randomized trial to investigate whether treatment with progesterone would increase the rates of live births and newborn survival among women with unexplained recurrent miscarriage. We randomly assigned women with recurrent miscarriages to receive twice-daily vaginal suppositories containing either 400 mg of micronized progesterone or matched placebo from a time soon after a positive urinary pregnancy test (and no later than 6 weeks of gestation) through 12 weeks of gestation. The primary outcome was live birth after 24 weeks of gestation. A total of 1568 women were assessed for eligibility, and 836 of these women who conceived naturally within 1 year and remained willing to participate in the trial were randomly assigned to receive either progesterone (404 women) or placebo (432 women). The follow-up rate for the primary outcome was 98.8% (826 of 836 women). In an intention-to-treat analysis, the rate of live births was 65.8% (262 of 398 women) in the progesterone group and 63.3% (271 of 428 women) in the placebo group (relative rate, 1.04; 95% confidence interval [CI], 0.94 to 1.15; rate difference, 2.5 percentage points; 95% CI, -4.0 to 9.0). There were no significant between-group differences in the rate of adverse events. Progesterone therapy in the first trimester of pregnancy did not result in a significantly higher rate of live births among women with a history of unexplained recurrent miscarriages. (Funded by the United Kingdom National Institute of Health Research; PROMISE Current Controlled Trials number, ISRCTN92644181.).
Body LiteracyMenstrual Cycle as Vital SignMenstrual EvaluationAdolescent Reference Ranges
Despite variations worldwide and within the U.S. population, median age at menarche has remained relatively stable-between 12 years and 13 years-across well-nourished populations in developed countries. Environmental factors, including socioeconomic conditions, nutrition, and access to preventive health care, may influence the timing and progression of puberty. A number of medical conditions can cause abnormal uterine bleeding, characterized by unpredictable timing and variable amount of flow. Clinicians should educate girls and their caretakers (eg, parents or guardians) about what to expect of a first menstrual period and the range for normal cycle length of subsequent menses. Identification of abnormal menstrual patterns in adolescence may improve early identification of potential health concerns for adulthood. It is important for clinicians to have an understanding of the menstrual patterns of adolescent girls, the ability to differentiate between normal and abnormal menstruation, and the skill to know how to evaluate the adolescent girl patient. By including an evaluation of the menstrual cycle as an additional vital sign, clinicians reinforce its importance in assessing overall health status for patients and caretakers.
Evidence is growing that the equilibrium between reactive oxygen species and antioxidants plays a vital role in women's reproductive health. The objective of this study was to evaluate variations in serum antioxidant concentrations across the menstrual cycle and associations between antioxidants and reproductive hormones and anovulation among healthy women. The BioCycle Study, a prospective cohort, followed 259 women aged 18-44 y for up to 2 menstrual cycles. Serum fat-soluble vitamin and micronutrient (α-tocopherol, γ-tocopherol, retinol, lutein, lycopene, and β-carotene), ascorbic acid, and reproductive hormone concentrations were measured 5-8 times/cycle. We used weighted linear mixed models to assess associations between antioxidants and hormone concentrations, after adjustment for age, race, body mass index, parity, sleep, pain medication use, total energy intake, concurrent hormones, serum cholesterol, F2-isoprostanes, and other antioxidants. Generalized linear models were used to identify associations with anovulation. Serum antioxidant concentrations varied across the menstrual cycle. Retinol and α-tocopherol were associated with higher estradiol [RR: 1.00 pg/mL (95% CI: 0.67, 1.34 pg/mL); RR: 0.02 pg/mL (95% CI: 0.003, 0.03 pg/mL), respectively] and testosterone [RR: 0.61 ng/dL (95% CI: 0.44, 0.78 ng/dL); RR: 0.01 ng/dL (95% CI: 0.001, 0.01 ng/dL), respectively]. Ascorbic acid was associated with higher progesterone (RR: 0.15 ng/mL; 95% CI: 0.05, 0.25 ng/mL) and with lower follicle-stimulating hormone (RR: -0.06 mIU/mL; 95% CI: -0.09, -0.03 mIU/mL). The ratio of αto γ-tocopherol was associated with an increased risk of anovulation (RR: 1.03; 95% CI: 1.01, 1.06). These findings shed new light on the intricate associations between serum antioxidants and endogenous hormones in healthy premenopausal women and support the hypothesis that concentrations of serum vitamins affect steroidogenesis even after adjustment for oxidative stress.
Luteinized unruptured follicle (LUF) syndrome is considered a cause of ovulation failure and a subtle cause of infertility. Preovulatory injection of human chorionic gonadotropin (HCG) prevents or treats LUF syndrome, but it has also occurred after the induction of ovulation with clomiphene/HMG and HCG. This study was designed for evaluation and comparison of LUF incidence in eligible infertile women undergoing two stimulation protocols (clomiphene + HMG and letrozole + HMG) in addition to intrauterine insemination (IUI). Some related factors were compared between LUF and non-LUF cycles as secondary outcomes. The study was designed as a prospective randomized controlled trial. Patients were randomized using a table of random numbers into two equal protocol groups. For group A, (n = 90) clomiphene citrate was administrated orally in doses of 100 mg/day, and group B (n = 90) orally received letrozole 5 mg/day from day 3 to 7 of the menstrual cycle. Then HMG 75IU/day was administered intramuscularly in both groups on day 8 of the menstrual cycle and the dose was adjusted on the basis of ovarian response. The optimum size of preovulatory follicles for the injection of HCG (10,000 IU) was considered 18-23 mm. The number and size of preovulatory follicles were assessed by vaginal ultrasound 12 h before HCG (D0). Endometrial thickness was measured as well. IUI was performed on all patients 38-40 h after HCG. The second ultrasound examination was performed to observe the evidence of oocyte releasing at the time of IUI (D1). If the follicles were unruptured, a third sonography was performed on day 7 after HCG (D7) to observe LUF syndrome. There was a significant difference between clomiphene-HMG and letrozole-HMG in LUF (p = 0.021) and pregnancy (p = 0.041). The complete LUF in letrozole-HMG was lower than the alternative group and the pregnancy rate was higher. The patients in the non-LUF group had higher midluteal progesterone and a thicker endometrium compared to LUF cycles (p = 0.039) and (p < 0.001). The results of our multivariate logistic regression indicate that size 18-19.9 mm leads to the complete LUF less than ≥22 mm [AOR: 0.25, P = 0.005], and in size 20- 21.9 mm as well [AOR: 0.17, P = 0.002]. Letrozole, with lower incidences of LUF, is more effective than clomiphene citrate for the induction of ovulation in IUI cycles. In our study, we illustrated that larger follicles of ≥22 mm diameter were associated with higher incidences of LUF. We recommend that further studies investigate and focus on the relationship between follicular size and/or full hormonal profiles and LUF.
Ethics Committee of the American Society for Reproductive Medicine, 2015·Fertility and Sterility
The purpose of this ASRM Practice Committee report is to provide clinicians with principles and strategies for the evaluation and treatment of couples with infertility associated with obesity. This revised document replaces the Practice Committee document titled, "Obesity an educational bulletin," last published in 2008 (Fertil Steril 2008;90:S21-9).
du Plessis SS et al., 2015·Journal of assisted reproduction and genetics
Marijuana has the highest consumption rate among all of the illicit drugs used in the USA, and its popularity as both a recreational and medicinal drug is increasing especially among men of reproductive age. Male factor infertility is on the increase, and the exposure to the cannabinoid compounds released by marijuana could be a contributing cause. The endocannabinoid system (ECS) is deeply involved in the complex regulation of male reproduction through the endogenous release of endocannabinoids and binding to cannabinoid receptors. Disturbing the delicate balance of the ECS due to marijuana use can negatively impact reproductive potential. Various in vivo and in vitro studies have reported on the empirical role that marijuana plays in disrupting the hypothalamus-pituitary-gonadal axis, spermatogenesis, and sperm function such as motility, capacitation, and the acrosome reaction. In this review, we highlight the latest evidence regarding the effect of marijuana use on male fertility and also provide a detailed insight into the ECS and its significance in the male reproductive system.
Choi BO et al., 2015·Korean journal of family medicine
Although several risk factors associated with reduced age at natural menopause (ANM) have been investigated, the results are inconsistent. Excessive stress, which leads to elevation of stress hormones, can also negatively affect reproductive ability, including by accelerating menopause. However, a direct association between stress level and ANM has not yet been demonstrated. Therefore, the object of this study was to investigate the association between stress level and ANM in Korean women. Study participants were Korean women between 40 and 70 years old who were in natural menopause during the 5th Korean National Health and Nutrition Examination Survey (n=3,176). The level of stress in daily life was estimated based on data from the mental health topics of the survey. We used the t-test and one-way analysis of variance to analyze the correlation between stress level and ANM. Regression (β) coefficients calculated by multiple regression analysis were used to estimate various factors affecting ANM. Women who experienced a high level of stress in daily life had a lower mean ANM than women with a low stress level (50.17±3.7 and 50.58±3.5 years, respectively), with a statistically significant correlation (P<0.05). This correlation was still observed after adjusting for age, body mass index, menstrual regularity, and personal income (P<0.05 for variables). In Korean women between 40 and 70 years of age who are in natural menopause, there is a statistically significant correlation between stress level and ANM. In particular, women who experience a high level of stress in daily life have reduced ANM.
The objective of the study was to evaluate whether anti-Müllerian hormone (AMH) is associated with fecundability among women with proven fecundity and a history of pregnancy loss.
This was a prospective cohort study within a multicenter, block-randomized, double-blind, placebo-controlled clinical trial ( clinicaltrials.gov , number NCT00467363).
The study was conducted at four US medical centers (2006-2012). Participating women were aged 18-40 years, with a history of one to two pregnancy losses who were actively attempting pregnancy. Time to human chorionic gonadotropin detected and clinical pregnancy were assessed using Cox proportional hazard regression models to estimate fecundability odds ratios (fecundability odds ratios with 95% confidence interval [CI]) adjusted for age, race, body mass index, income, low-dose aspirin treatment, parity, number of previous losses, and time since most recent loss. Analyses examined low (<1.00 ng/mL, n = 124); normal (referent 1.00-3.5 ng/mL, n = 595); and high (>3.5 ng/mL, n = 483). Of the 1202 women with baseline AMH levels, 82 women with low AMH (66.1%) achieved an human chorionic gonadotropin detected pregnancy, compared with 383 with normal AMH (65.2%) and 315 with high AMH level (65.2%). Low or high AMH levels relative to normal AMH (referent) were not associated with fecundability (low fecundability odds ratios 1.13, 95% CI 0.85-1.49; FOR 1.04, 95% CI 0.87-1.24). Lower and higher AMH values were not associated with fecundability in unassisted conceptions in a cohort of fecund women with a history of one or two prior losses. Our data do not support routine AMH testing for preconception counseling in young, fecund women.
Perimenopause/MenopauseProgesterone vs ProgestinBreast Cancer RiskPhysiological Effects
Provide evidence-based recent data on oral micronized progesterone (OMP) and progestins in menopausal hormonal therapy (MHT). Medroxyprogesterone acetate (MPA) increases breast cancer acting through the glucocorticoid receptor; progestins in MHT increase thrombosis more than oral estrogens; MPA, but not OMP or other progestins, increase monocyte cell endothelium adhesion; MPA and estradiol (E2)/MPA have negative brain effects, whereas E2/progesterone (P4) has neuroregenerative brain effects. The 'window of opportunity' cardiovascular disease hypothesis is not supported by a randomized controlled trial showing that transdermal estradiol with sequential OMP in early menopause does not prevent increased carotid intimal media thickness; P4 in the cardiac electrical system opposes E2 effects and prevents sudden death/long QT syndrome; transdermal estradiol/OMP does not increase venous thromboembolism in observational data. P4 decreases breast cell proliferation and improves prognosis through P4 receptor alteration of estrogen receptor α genetic effects; OMP with conjugated equine estrogen (CEE)/estrogen (E)/E2 does not increase breast cancer in two prospective cohorts, one population-based. Endometrial cancer is increased in MHT of CEE/E/E2+cyclic OMP at 200 mg/day.
New data show CEE/E/E2+MPA/P mechanisms for negative breast cancer, venous thromboembolism, cardiovascular system, and brain effects. OMP/P4 counterbalances CEE/E/E2-related negative effects on breast cancer and long QT syndrome. OMP effectively treats vasomotor symptoms and sleep disturbances, and could safely be used alone for symptomatic menopause.
A personalized treatment strategy formalizes evidence-based treatment selection by mapping patient information to a recommended treatment. Personalized treatment strategies can produce better patient outcomes while reducing cost and treatment burden. Thus, among clinical and intervention scientists, there is a growing interest in conducting randomized clinical trials when one of the primary aims is estimation of a personalized treatment strategy. However, at present, there are no appropriate sample size formulae to assist in the design of such a trial. Furthermore, because the sampling distribution of the estimated outcome under an estimated optimal treatment strategy can be highly sensitive to small perturbations in the underlying generative model, sample size calculations based on standard (uncorrected) asymptotic approximations or computer simulations may not be reliable. We offer a simple and robust method for powering a single stage, two-armed randomized clinical trial when the primary aim is estimating the optimal single stage personalized treatment strategy. The proposed method is based on inverting a plugin projection confidence interval and is thereby regular and robust to small perturbations of the underlying generative model. The proposed method requires elicitation of two clinically meaningful parameters from clinical scientists and uses data from a small pilot study to estimate nuisance parameters, which are not easily elicited. The method performs well in simulated experiments and is illustrated using data from a pilot study of time to conception and fertility awareness.
Vettori D et al., 2015·Journal of Neonatal-Perinatal Medicine
Aplasia cutis congenita (ACC) is rare skin disorder of newborns that has been linked to both assisted reproductive technology (ART) and feto-reduction procedures. ACC is characterized by well-demarcated lesions that are devoid of all skin layers. Group-V ACC presents with a distinctive and symmetrical distribution pattern. It is thought to result from an insult to the fetus after concomitant twin demise and is almost exclusively reported in monochorionic gestations.A 41-year-old female with an in vitro fertilization (IVF) assisted tri-chorionic gestation subsequently underwent selective feto-reduction of Fetus C. The patient delivered two pre-term neonates secondary to pre-eclampsia. The initial exam of Twin B showed extensive, well-demarcated, symmetrical areas devoid of any skin over the anterior and lateral trunk, extending up the lateral thoracic walls. Chest and abdominal viscera were visible through a thin fibrous membrane. The skin defects were managed conservatively with twice-daily dressings of Aquaphor, and Vaseline gauze. The areas of aplasia slowly contracted, though residual scarring was noted. After four weeks in the NICU, most of the areas were healed.ACC in multi-fetal pregnancies is a rare, but well-described complication. This is, to our knowledge, the first reported case in a tri-chorionic IVF gestation after feto-reduction. With increased incidence of ART-associated pregnancies and the use of feto-reduction for higher order gestations, this may become more common. Neonates often require specialized intensive care. Conservative management usually will suffice, although surgical grafting may be required. Physicians should be aware of this condition and counsel their feto-reduction patients of the risk.
Chronic endometritis (CE) is a local inflammatory disease characterized by unusual plasmacyte infiltration in the endometrial stromal areas. CE has been neglected in gynecologic practice, as it is a less symptomatic benign disease that requires demanding and time-consuming histopathologic examinations for the definite diagnosis. Recent studies, however, suggest the association of CE with infertility and obstetric and neonatal complications. In this review article, we aimed to update the knowledge on epidemiology, etiology, and pathogenesis of CE as well as discuss its clinical management from diagnosis to treatment.
Kristen M Sokalski et al., 2016·Clin Endocrinol (Oxf)
To investigate the prevalence of endocrine disturbances in a group of HIV-positive (HIV+) women and to identify factors affecting presence of these disorders. To examine specifically whether cellular ageing, as measured by leukocyte telomere length (LTL), is correlated with the presence of endocrine disturbance.
A cross-sectional retrospective substudy of an ongoing prospective cohort study. Adult HIV+ (≥19 years) women enrolled in the CARMA (Children AntiRetrovirals and Markers of Aging) cohort study (N = 192). Prevalences of T2DM, glucose intolerance, dyslipidaemia, thyroid disorders, adrenal insufficiency, hypogonadism, primary ovarian insufficiency (POI), demographics, HIV and hepatitis C virus (HCV) infection status, baseline LTL, combined antiRetroviral therapy (cART) and substance exposures were collected. Statistical analysis included univariable followed by multivariable Poisson regression and step-wise reduction to refine the multivariable model. Prevalence of any endocrine abnormality was 58% (dyslipidaemia 43%, glucose intolerance/T2DM 13%, thyroid disorders 15%). In multivariable analysis, age was associated with number and type (any, glucose, lipid) of abnormality, while increasing body mass index (BMI) was associated with number of diagnoses and with glucose metabolism disorders. Interestingly, peak HIV pVL ≥100 000 copies/ml was associated with any abnormality, total number of disorders and presence of a thyroid disorder, while any disorder, glucose abnormalities and dyslipidaemia were negatively associated with alcohol use. LTL was not associated with number or type of endocrine abnormalities in this study. Further studies examining the relationship between duration and extent of exposure to HIV viraemia in relation to developing abnormal endocrine function are warranted.
Brown SA et al., 2015·Journal of diabetes science and technology
Factors influencing glycemic variability in type 1 diabetes (T1D) may play a significant role in the refinement of closed loop insulin administration. Phase of menstrual cycle is one such factor that has been inadequately investigated. We propose that unique individual patterns can be constructed and used as parameters of closed loop systems. Women with T1D on continuous subcutaneous insulin infusion and continuous glucose monitoring were studied for 3 consecutive menstrual cycles. Ovulation prediction kits and labs were used to confirm phase of menstrual cycle. Glycemic risks were assessed using the low- and high blood glucose indices (LBGI and HBGI). Insulin sensitivity (SI) was estimated using a Kalman filtering method from meal and insulin data. Overall change significance for glycemic risks was assessed by repeated measures ANOVA, with specific phases emphasized using contrasts. Ovulation was confirmed in 33/36 cycles studied in 12 subjects (age = 33.1 ± 7.0 years, BMI = 25.7 ± 2.9 kg/m(2), A1c = 6.8 ± 0.7%). Risk for hyperglycemia changed significantly during the cycle (P = .023), with HBGI increasing until early luteal phase and returning to initial levels thereafter. LBGI was steady in the follicular phase, decreasing thereafter but not significantly. SI was depressed during the luteal phase when compared to the early follicular phase (P ≤ .05). Total daily insulin, carbohydrates, or calories did not show any significant fluctuations. Women with T1D have glycemic variability changes that are specific to the individual and are linked to phase of cycle. An increased risk of hyperglycemia was observed during periovulation and early luteal phases compared to the early follicular phase; these changes appear to be associated with decreased insulin sensitivity during the luteal phase.
Very few studies describe the obstetric and neonatal outcome of spontaneous pregnancies in women with irregular menstrual cycles. However, menstrual cycle irregularities are common and may be associated with increased risk, and women who develop pregnancy complications more frequently recollect irregular menstrual cycles before the time of conception in case-control studies. This retrospective cohort study compares obstetric and neonatal outcomes in spontaneous singleton pregnancies in 3440 primiparous Danish women stratified according to menstrual cycle regularity. All pregnancies delivered after 22 weeks of gestation and had a nuchal translucency examination at Copenhagen University Hospital Hvidovre between 1 January 2009 and 31 December 2010. Menstrual cycle irregularity was defined as more than 7 days' deviation between self-reported and ultrasound examination-based gestational age. Outcome measures were gestational diabetes, hypertension, preeclampsia, preterm premature rupture of membranes, preterm birth, prolonged pregnancy, birthweight, umbilical artery pH <7.1, APGAR <7 after 5 min, admission to neonatal intensive care unit and stillbirth. Women with more than 7 days' deviation between self-reported and ultrasound examination-based gestational age were compared with women with a deviation of 7 days or less. Irregular menstrual cycle before conception increases the risk of preeclampsia (7.9% vs. 5.2%, p < 0.05) and low birthweight (6.0% vs. 3.6%, p < 0.05) in spontaneous pregnancies, but reduces the risk of prolonged pregnancy (1.4% vs. 4.7%, p < 0.001). Irregular menstrual cycle before conception is associated with increased risk of adverse obstetric and neonatal outcome.
To evaluate the relationship between epigenetic patterns in sperm and fecundity.
Prospective study.
Academic andrology and in vitro fertilization laboratory. PATIENT(S): Twenty-seven semen samples from couples who conceived within 2 months of attempting a pregnancy and 29 semen samples from couples unable to achieve a pregnancy within 12 months. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Genomewide assessment of differential sperm DNA methylation and standard semen analysis. RESULT(S): We analyzed DNA methylation alterations associated with fecundity in 124 semen samples, and identified regions of interest in 27 semen samples from couples who conceived within 2 months of attempting a pregnancy and a total of 29 semen samples from couples who were unable to achieve a pregnancy within 12 months. No differences in sperm count, sperm morphology, or semen volume were observed between the patients achieving a pregnancy within 2 months of study time and those not obtaining a pregnancy within 12 months. However, using data from the human methylation 450k array analysis we did identify two genomic regions with statistically significantly decreased (false discovery rate <0.01) methylation and three genomic regions with statistically significantly increased methylation in the failure-to-conceive group. The only two sites where decreased methylation was associated with reduced fecundity are at closely related genes known to be expressed in sperm, HSPA1L and HSPA1B. CONCLUSION(S): Our data suggest that there are genomic loci where DNA methylation alterations are associated with decreased fecundity. We have thus identified candidate loci for future study to verify these results and investigate the causative or contributory relationship between altered sperm methylation and decreased fecundity.
To determine agreement on endometriosis diagnosis between real-time laparoscopy and subsequent expert review of digital images, operative reports, magnetic resonance imaging (MRI), and histopathology, viewed sequentially.
Inter-rater agreement study.
Five urban surgical centres. Women, aged 18-44 years, who underwent a laparoscopy regardless of clinical indication. A random sample of 105 women with and 43 women without a postoperative endometriosis diagnosis was obtained from the ENDO study. Laparoscopies were diagnosed, digitally recorded, and reassessed. Inter-observer agreement of endometriosis diagnosis and staging according to the revised American Society for Reproductive Medicine criteria. Prevalence and bias-adjusted kappa values (κ) were calculated for diagnosis, and weighted κ values were calculated for staging. Surgeons and expert reviewers had substantial agreement on diagnosis and staging after viewing digital images (n = 148; mean κ = 0.67, range 0.61-0.69; mean κ = 0.64, range 0.53-0.78, respectively) and after additionally viewing operative reports (n = 148; mean κ = 0.88, range 0.85-0.89; mean κ = 0.85, range 0.84-0.86, respectively). Although additionally viewing MRI findings (n = 36) did not greatly impact agreement, agreement substantially decreased after viewing histological findings (n = 67), with expert reviewers changing their assessment from a positive to a negative diagnosis in up to 20% of cases. Although these findings suggest that misclassification bias in the diagnosis or staging of endometriosis via visualised disease is minimal, they should alert gynaecologists who review operative images in order to make decisions on endometriosis treatment that operative reports/drawings and histopathology, but not necessarily MRI, will improve their ability to make sound judgments. Endometriosis diagnosis and staging agreement between expert reviewers and operating surgeons was substantial.
Thyroid autoimmunity with normal thyroid function is associated with recurrent miscarriage (RM), but the association with live birth is less clear. Therefore, we determined the association between thyroid peroxidase antibodies (TPO-Ab) and live-birth rate (LBR) in a retrospective cohort of euthyroid women with unexplained RM. We included 202 women of which 28 were TPO-Ab positive (13.9%) and 174 were TPO-Ab negative. TPO-Ab positive women (n = 10) without levothyroxine treatment had a lower LBR (29%) compared to TPO-Ab negative women (51%) (HR 0.23, 0.07-0.72, p = 0.012). The LBR in women with TPO-Ab receiving levothyroxine was not different compared women without TPO-Ab (60% versus 51%, p = 0.50). In conclusion, TPO-Ab are associated with a lower LBR in euthyroid women with unexplained RM and these women may benefit from treatment with levothyroxine.