Namavar Jahromi B MD et al., 2018·Iranian journal of medical sciences
Ovarian hyperstimulation syndrome (OHSS) is a serious complication of ovulation induction that usually occurs after gonadotropin stimulation, followed by human chorionic gonadotropin administration, for infertility treatment. The existing knowledge about the pathophysiology, risk factors, and primary and secondary methods for the prevention of OHSS is reviewed in this manuscript. The clinical manifestations and characteristics of mild, moderate, severe, and critical forms of the syndrome are defined. The methods of handling affected cases as outpatient or in-hospital management methods as well as indications for hospitalization are summarized in this review. The clinical and biochemical routes of assessing and monitoring hospitalized patients with OHSS, various drugs and medical treatment strategies including indications for aspiration of the ascitic fluid and pleural effusion, and also rare indications for surgery are briefly explained in this article. Severe OHSS, which two decades ago was considered an iatrogenic life-threatening condition, can now be effectively prevented or managed during the early stages. An OHSS-free clinic can be established nowadays by carefully considering the endocrinology of ovulation and using appropriate and dose-adjusted pharmaceutical agents, which are summarized and discussed in this review.
Contraception/ComparisonReproductive Outcome ConsequencesContraceptive Influence on Young WomenAdolescent Reproductive Health
Oral contraceptives (OCs) are often prescribed to adolescents and young adults for the treatment of health problems and to avoid unwanted pregnancies. We hypothesized that the use of OCs, among adolescents and young adults, is associated with a greater likelihood of pregnancy, abortion, sexually transmitted diseases (STDs), pelvic inflammatory disease (PID), and sexual behaviors that will enhance those problems (i.e., earlier sexual debut and more sexual partners) than adolescents and young adults not using OCs. To test this hypothesis, data from 1,365 adolescents and young adults in the 2011-2013 National Survey of Family Growth (NSFG) were used to describe the influence of ever use of OCs on ever having sex, sexual debut, multiple sexual partners, STDs, PID, pregnancy, and abortion. A secondary purpose was to evaluate protective factors from unhealthy sexual practices like religiosity, church attendance, and intact families. We found that the "ever use" of OCs by US adolescents and young adults results in a greater likelihood of ever having sex, STDs, PID, pregnancy, and abortion compared with those adolescents and young adults who never used OCs. Furthermore, those adolescents who ever used OCs had significantly more male sexual partners than those who never used OCs, and they also had an earlier sexual debut by almost two years. Conversely, we found that frequent church attendance, identification of the importance of religion, and having an intact family among adolescents were associated with less likelihood of unsafe sexual practices. We concluded that the use of OCs by adolescents and young adults might be considered a health risk. Further research is recommended to confirm these associations.
The purpose of this article was to show the correlation between contraceptive use in adolescents and negative sexual outcomes. We used data from the 2011-2013 NSFG and demonstrated that never married adolescents who used oral hormonal contraception were three times more likely to have an STD, have PID, and to become pregnant, and, surprisingly, ten times more likely of having an abortion compared to noncontracepting adolescents. These are outcomes that contraception is intended to prevent. These data also showed that the contraceptors had significantly more male partners than their contraceptive counterparts. Protective factors such as church attendance and family cohesiveness were associated with a decreased likelihood of sexual activity.
To assess efficacy, comparative effectiveness, and harms of psychological and pharmacological treatments for adults with posttraumatic stress disorder (PTSD) and to update the original 2013 review. MEDLINE(®), CINAHL(®), Cochrane Library, Cochrane Clinical Trials Registry, PILOTS (Published International Literature on Traumatic Stress), PsycINFO(®), and reference lists of published literature (May 2012–September 2017). Two investigators independently selected, extracted data from, and rated risk of bias of relevant studies. We conducted meta-analyses or network meta-analyses using random-effects models when we had evidence from three or more studies with low heterogeneity. We graded strength of evidence (SOE) following established Agency for Healthcare Research and Quality guidance. We included 193 randomized controlled trials (207 articles) for this review. Several psychological treatments were associated with the reduction of PTSD symptoms and loss of PTSD diagnosis compared with inactive comparators; high SOE supports efficacy of cognitive behavioral therapy (CBT)-exposure and CBT-mixed treatments, and moderate SOE supports efficacy of cognitive processing therapy (CPT), cognitive therapy (CT), eye movement desensitization and reprocessing (EMDR), and narrative exposure therapy (NET). When directly comparing two treatments of interest, moderate SOE favors CBT-exposure over relaxation therapy. Several pharmacological treatments reduced PTSD symptoms; moderate SOE supports the efficacy of fluoxetine, paroxetine, and venlafaxine compared with placebo. Our network meta-analysis (33 trials; N=4,817) of Clinician-Administered PTSD Scale (CAPS)-measured PTSD symptoms showed no differences in effectiveness between medications with at least moderate SOE of efficacy (fluoxetine, paroxetine, and venlafaxine) (low SOE for no difference). Studies provided insufficient strength of evidence for serious adverse events associated with any treatments of interest. The majority of psychological studies reported no information about adverse events. Among pharmacological treatments with evidence of efficacy (moderate SOE), we found increased risk of nausea with venlafaxine compared with placebo (moderate SOE). Our review found insufficient strength of evidence for the comparative effectiveness of any psychological versus pharmacological treatment and for differences in the efficacy or comparative effectiveness of treatments by patient characteristics (e.g., co-occurring conditions) or type, number, severity, or chronicity of trauma exposure(s). We did not find evidence for many of our outcomes of interest or interventions of interest, including the newer treatments added since our prior review. Several psychological and pharmacological treatments have moderate to high SOE of efficacy for treating adults with PTSD. Future research is needed on the comparative effectiveness of treatments (including different comparisons of psychological and pharmacological treatments), differences in treatment benefits by trauma type or other patient characteristics, and adverse events associated with treatments.
To compare the prevalence of chronic endometritis (CE) when different diagnostic methods are used. Prospective observational study. University-affiliated hospital. PATIENT(S): Four groups of women were studied, including women with proven fertility (Fertile; n = 40), unexplained recurrent miscarriage (RM; n = 93), recurrent implantation failure (RIF; n = 39), and infertile subjects undergoing endometrial scratch in a natural cycle preceding frozen-thawed embryo transfer (Infertility; n = 48). INTERVENTION(S): Endometrial biopsy was performed precisely 7 days after LH surge (LH+7). Plasma cells were identified by means of traditional hematoxylin and eosin (HE) staining and by means of immunohistochemistry (IHC) for Syndecan-1 (CD138). MAIN OUTCOME MEASURE(S): Prevalence of CE. RESULT(S): The use of CD138 epitope was more sensitive than HE staining in identifying plasma cells. The use of plasma cell count per unit area had the lowest observer variability compared with cell count per ten randomly chosen high-power fields and cell count per section. Using this method, the prevalence of CE in women with RM, RIF, and Infertility were 10.8%, 7.7%, and 10.4%, respectively, not significantly higher than that of Fertile subjects (5.0%). CONCLUSION(S): Using what may be a new method of plasma cell assessment, it appears that the prevalence rates of CE reported in many earlier studies may have been overestimated. CLINICAL ChiCTR-IOC-16007882.
Laughlin-Tommaso SK et al., 2018·Menopause (New York, N.Y.)
The aim of the study was to determine the long-term risk of cardiovascular disease and metabolic conditions in women undergoing hysterectomy with bilateral ovarian conservation compared with age-matched referent women. Using the Rochester Epidemiology Project records-linkage system, we identified 2,094 women who underwent hysterectomy with ovarian conservation for benign indications between 1980 and 2002 in Olmsted County, Minnesota. Each woman was age-matched (±1 y) to a referent woman residing in the same county who had not undergone prior hysterectomy or any oophorectomy. These two cohorts were followed historically to identify de novo cardiovascular or metabolic diagnoses. We estimated hazard ratios (HRs) and 95% CIs using Cox proportional hazards models adjusted for 20 preexisting chronic conditions and other potential confounders. We also calculated absolute risk increases and reductions from Kaplan-Meier estimates. Over a median follow-up of 21.9 years, women who underwent hysterectomy experienced increased risks of de novo hyperlipidemia (HR 1.14; 95% CI, 1.05-1.25), hypertension (HR 1.13; 95% CI, 1.03-1.25), obesity (HR 1.18; 95% CI, 1.04-1.35), cardiac arrhythmias (HR 1.17; 95% CI, 1.05-1.32), and coronary artery disease (HR 1.33; 95% CI, 1.12-1.58). Women who underwent hysterectomy at age ≤35 years had a 4.6-fold increased risk of congestive heart failure and a 2.5-fold increased risk of coronary artery disease. Even with ovarian conservation, hysterectomy is associated with an increased long-term risk of cardiovascular and metabolic conditions, especially in women who undergo hysterectomy at age ≤35 years. If these associations are causal, alternatives to hysterectomy should be considered to treat benign gynecologic conditions.
Kurdi MS et al., 2018·Indian journal of anaesthesia
The menstrual cycle is a physiological phenomenon that is accompanied by several hormonal fluctuations involving oestrogen and progesterone. Oestrogen and progesterone exert several physiological effects. There are many questions pertaining to the influence of the physiology of menstruation on anaesthesia. We attempted to find out whether the phase of the menstrual cycle can alter the physiological functions during anaesthesia, the perioperative management and outcomes. We performed a literature search in Google Scholar, PubMed and Cochrane databases for original and reviewed articles on the phases of the menstrual cycle and their relation to anaesthesia-related physiological parameters to find an answer to these questions. Many studies have shown that women, perimenstrually, may have increased pain perception, exacerbation of systemic diseases, vocal cord/peripheral oedema and post-operative nausea and vomiting (PONV). Some of the other notable findings in most studies were sleep disturbances in the luteal phase (LP), increased occurrence of PONV in the ovulatory phase and a lower requirement of intravenous sedative and anaesthetic drug requirements in the LP. We found contradictory results concerning pain perception and PONV in relation to the follicular and LPs. However, we found that literature regarding the phase of the menstrual cycle and the haemodynamic response to intubation, anaesthesia-induced hypnosis and perioperative blood loss is relatively scarce. Thus, there is a need to conduct good quality research on these topics.
Contraception/ComparisonHIV-1 Replication RiskGlucocorticoid Receptor EffectsContraceptive Immunologic Effects
Open Access
High usage of progestin-only injectable contraceptives, which include the intramuscular injectables depo-medroxyprogesterone acetate (DMPA-IM, Depo-Provera) and norethisterone (NET) enanthate (NET-EN or Nur-Isterate), correlates worldwide with areas of high HIV-1 prevalence. Epidemiological data show a significant association between usage of DMPA-IM and increased HIV-1 acquisition but no such association from limited data for NET-EN. Whether MPA and NET have similar effects on HIV-1 acquisition and pathogenesis, and the relationship between these effects and the dose of MPA, are critical issues for women's health and access to suitable and safe contraceptives. We show for the first time that MPA, unlike NET, significantly increases HIV-1 replication in peripheral blood mononuclear cells (PBMCs) and a cervical cell line model. The results provide novel evidence for a biological mechanism whereby MPA, acting via the glucocorticoid receptor (GR), increases HIV-1 replication by at least in part increasing expression of the CCR5 HIV-1 coreceptor on target T-lymphocytes. MPA, unlike NET, also increases activation of T-cells and increases the CD4/CD8 ratio, suggesting that multiple mechanisms are involved in the MPA response. Our data offer strong support for different biological mechanisms for MPA versus NET, due to their differential GR activity. The dose-dependence of the MPA response suggests that significant effects are observed within the range of peak serum levels of progestins in DMPA-IM but not NET-EN users. Dose-response results further suggest that effects of contraceptives containing MPA on HIV-1 acquisition and disease progression may be critically dependent on dose, time after injection and intrinsic factors that affect serum concentrations in women.
InfertilityTamoxifen for Thin EndometriumEndometrial Thickness ImprovementClomiphene Alternative Approaches
Open Access
Gonadotropin stimulation is used as the second line of treatment in patients with thin endometrium following clomiphene citrate (CC) administration, which is associated with higher cost, multiple births, and ovarian hyperstimulation syndrome. Tamoxifen (TMX), a selective estrogen receptor modulator, acts as an agonist on the endometrium. The objective of the present study was to compare the efficacy of low-dose CC, TMX, and gonadotropins in women with thin endometrium (<7 mm) following Clomiphene in intrauterine insemination (IUI) cycles. A prospective observational study between December 2011 and June 2013 was carried out in a tertiary infertility center. Women (n = 502) undergoing IUI with endometrium <7 mm after 100 mg CC were included in the study and divided into three treatment groups. Women in Group A (n = 182, cycles = 364) received clomiphene (50 mg/day from day 3 to 7), Group B (n = 179, cycles = 342) received TMX (40 mg/day from day 3 to 7), and Group C (n = 141, cycles = 226) received continuous urine-derived follicle-stimulating hormone 75-150 IU from day 3 onward until human chorionic gonadotropin injection. Endometrial thickness (ET), pregnancy rate, and live birth rate were considered as main outcome measures. Multiple comparisons using one-way ANOVA and Schiff's test were performed. Pregnancy and live birth rate were significantly higher (P < 0.004) in TMX and gonadotropin groups compared to clomiphene. A number of follicles in the TMX group were found to be lower (P < 0.001) compared to other two groups. In polycystic ovary syndrome patients, ovulation induction with TMX resulted in inadequate response in more than half of the cycles. TMX can improve ET and live birth rate in patients with thin endometrium after clomiphene.
Contraception/ComparisonArterial StiffnessCycle Phase and Arterial ComplianceSex Differences in Vascular Health
Priest SE et al., 2018·Am J Physiol Heart Circ Physiol
Arterial stiffness is associated with increased cardiovascular disease risk. Previous sex-based investigations of local and central stiffness report inconsistent findings and have not controlled for menstrual cycle phase in women. There is also evidence that sex hormones influence the vasculature, but their impact on arterial stiffness across a natural menstrual (NAT) or oral contraceptive pill (OCP) cycle has been understudied. This study sought to 1) examine potential sex differences in local and central stiffness, 2) compare stiffness profiles between NAT and OCP cycles, and 3) investigate the relationship between duration of OCP use and arterial stiffness. Sex hormone concentrations, β-stiffness index (local stiffness), and carotid-femoral pulse wave velocity [cfPWV (central stiffness)] were assessed in 53 healthy adults (22 ± 3 yr old, 20 men, 15 NAT women, and 18 OCP women). All participants men on the same day and time 1 wk apart, NAT women in menstrual, midfollicular and luteal phases of the menstrual cycle, and OCP women in placebo, early active and late active pill phases. β-Stiffness was higher in men than NAT and OCP women ( P < 0.001), whereas cfPWV was similar between groups ( P = 0.09). β-Stiffness and cfPWV did not differ across or between NAT and OCP cycles ( P > 0.05 for both) and were not associated with duration of OCP use (β-stiffness: r = 0.003, P = 0.99; r = -0.26, P = 0.30). The apparent sex differences in local, but not central, stiffness highlight the importance of assessing both indexes in comparisons between men and women. Furthermore, fluctuating sex hormone levels do not appear to influence β-stiffness or cfPWV. Therefore, these stiffness indexes may need to be assessed during only one cycle phase in women in future investigations. NEW & NOTEWORTHY We observed higher local, but not central, arterial stiffness in men than women. We also demonstrated that there are no differences in arterial stiffness between naturally cycling women and women who use monophasic oral contraceptive pills, and that the duration of oral contraceptive pill use does not influence arterial stiffness.
General OB/GYNLow-Dose Naltrexone for Crohn DiseaseInflammatory Bowel Disease TreatmentOpioid Antagonist Anti-Inflammatory Use
Crohn's disease is a transmural, relapsing inflammatory condition afflicting the digestive tract. Opioid signalling, long known to affect secretion and motility in the gut, has been implicated in the inflammatory cascade of Crohn's disease. Low dose naltrexone, an opioid antagonist, has garnered interest as a potential therapy. The primary objective was to evaluate the efficacy and safety of low dose naltrexone for induction of remission in Crohn's disease. A systematic search of MEDLINE, Embase, PubMed, CENTRAL, and the Cochrane IBD Group Specialized Register was performed from inception to 15 January 2018 to identify relevant studies. Abstracts from major gastroenterology conferences including Digestive Disease Week and United European Gastroenterology Week and reference lists from retrieved articles were also screened.
Randomized controlled trials of low dose naltrexone (LDN) for treatment of active Crohn's disease were included. Data were analyzed on an intention-to-treat basis using Review Manager (RevMan 5.3.5). The primary outcome was induction of clinical remission defined by a Crohn's disease activity index (CDAI) of < 150 or a pediatric Crohn's disease activity index (PCDAI) of < 10. Secondary outcomes included clinical response (70or 100-point decrease in CDAI from baseline), endoscopic remission or response, quality of life, and adverse events as defined by the included studies. Risk ratios (RR) and 95% confidence intervals (CI) were calculated for dichotomous outcomes. The methodological quality of included studies was evaluated using the Cochrane risk of bias tool. The overall quality of the evidence supporting the primary outcome and selected secondary outcomes was assessed using the GRADE criteria. Two studies were identified (46 participants). One study assessed the efficacy and safety of 12 weeks of LDN (4.5 mg/day) treatment compared to placebo in adult patients (N = 34). The other study assessed eight weeks of LDN (0.1 mg/kg, maximum 4.5 mg/day) treatment compared to placebo in pediatric patients (N = 12). The primary purpose of the pediatric study was to assess safety and tolerability. Both studies were rated as having a low risk of bias. The study in adult patients reported that 30% (5/18) of LDN treated patients achieved clinical remission at 12 weeks compared to 18% (3/16) of placebo patients, a difference that was not statistically significant (RR 1.48, 95% CI 0.42 to 5.24). The study in children reported that 25% of LDN treated patients achieved clinical remission (PCDAI < 10) compared to none of the patients in the placebo group, although it was unclear if this result was for the randomized placebo-controlled trial or for the open label extension study. In the adult study 70-point clinical response rates were significantly higher in those treated with LDN than placebo. Eighty-three per cent (15/18) of LDN patients had a 70-point clinical response at week 12 compared to 38% (6/16) of placebo patients (RR 2.22, 95% CI 1.14 to 4.32). The effect of LDN on the proportion of adult patients who achieved a 100-point clinical response was uncertain. Sixty-one per cent (11/18) of LDN patients achieved a 100-point clinical response compared to 31% (5/16) of placebo patients (RR 1.96, 95% CI 0.87 to 4.42). The proportion of patients who achieved endoscopic response (CDEIS decline > 5 from baseline) was significantly higher in the LDN group compared to placebo. Seventy-two per cent (13/18) of LDN patients achieved an endoscopic response compared to 25% (4/16) of placebo patients (RR 2.89; 95% CI 1.18 to 7.08). However, there was no statistically significant difference in the proportion of patients who achieved endoscopic remission. Endoscopic remission (CDEIS < 3) was achieved in 22% (4/18) of the LDN group compared to 0% (0/16) of the placebo group (RR 8.05; 95% CI 0.47 to 138.87). Pooled data from both studies show no statistically significant differences in withdrawals due to adverse events or specific adverse events including sleep disturbance, unusual dreams, headache, decreased appetite, nausea and fatigue. No serious adverse events were reported in either study. GRADE analyses rated the overall quality of the evidence for the primary and secondary outcomes (i.e. clinical remission, clinical response, endoscopic response, and adverse events) as low due to serious imprecision (sparse data). AUTHORS' Currently, there is insufficient evidence to allow any firm conclusions regarding the efficacy and safety of LDN used to treat patients with active Crohn's disease. Data from one small study suggests that LDN may provide a benefit in terms of clinical and endoscopic response in adult patients with active Crohn's disease. Data from two small studies suggest that LDN does not increase the rate of specific adverse events relative to placebo. However, these results need to be interpreted with caution as they are based on very small numbers of patients and the overall quality of the evidence was rated as low due to serious imprecision. Further randomized controlled trials are required to assess the efficacy and safety of LDN therapy in active Crohn's disease in both adults and children.
Well-differentiated papillary mesothelioma is a rare tumor occurring predominantly in the peritoneum of young women, a few with history of asbestos exposure. A 28-year-old woman presented with ascites and pain abdomen. Ultrasonography and computed tomography scan of the abdomen revealed a mass in the retroperitoneum measuring 15 cm × 12 cm. Histopathological examination along with immunohistochemistry (IHC) confirmed it to be a papillary mesothelioma in the peritoneum. It is difficult to differentiate from more common malignant mesothelioma and papillary adenocarcinoma, which also have poorer prognosis. The difficulty can be resolved by clinico-radiological correlation along with histopathological examination and IHC.
Harris HR et al., 2018·Human reproduction (Oxford, England)
Is there an association between intake of fruits and vegetables and risk of laparoscopically confirmed endometriosis? Higher intake of fruits, particularly citrus fruits, is associated with a lower risk of endometriosis. Two case-control studies have examined the associations between fruit and vegetable intake and endometriosis risk with contrasting results. Diets rich in fruits and vegetables include higher levels of pro-vitamin A nutrients (alpha-carotene, beta-carotene, beta-cryptoxanthin) and women with endometriosis have been reported to have lower intake of vitamin A than women without endometriosis. STUDY DESIGN SIZE, A prospective cohort study using data collected from 70 835 premenopausal women from 1991 to 2013 as part of the Nurses' Health Study II cohort. PARTICIPANTS/MATERIALS, SETTING, Diet was assessed with a validated food frequency questionnaire (FFQ) every 4 years. Cases were restricted to laparoscopically confirmed endometriosis. Cox proportional hazards models were used to calculate rate ratios (RR) and 95% CI. MAIN During 840 012 person-years of follow-up, 2609 incident cases of laparoscopically confirmed endometriosis were reported (incidence rate = 311 per 100 000 person-years). We observed a non-linear inverse association between higher fruit consumption and risk of laparoscopically confirmed endometriosis (Psignificance of the curve = 0.005). This inverse association was particularly evident for citrus fruits. Women consuming ≥1 servings of citrus fruits/day had a 22% lower endometriosis risk (95% CI = 0.69-0.89; Ptrend = 0.004) compared to those consuming <1 serving/week. No association was observed between total vegetable intake and endometriosis risk. However, women consuming ≥1 servings/day cruciferous vegetables had a 13% higher risk of endometriosis (95% CI = 0.95-1.34; Ptrend = 0.03) compared to those consuming <1 serving/week. Of the nutrients examined, only beta-cryptoxanthin intake was significantly associated with lower endometriosis risk (RR fifth quintile = 0.88; 95% CI = 0.78-1.00; Ptrend = 0.02). LIMITATIONS Some error in the self-reporting of dietary intake is expected, however, use of a validated FFQ and examining diet prospectively across multiple time points, make it unlikely that this non-differential misclassification strongly influenced the results. Our findings suggest that a higher intake of fruits, particularly citrus fruits, is associated with a lower risk of endometriosis, and beta-cryptoxanthin in these foods may partially explain this association. In contrast to what we hypothesized, consumption of some vegetables increased endometriosis risk which may indicate a role of gastrointestinal symptoms in both the presentation and exacerbation of endometriosis-related pain; however, it is not clear what components of these foods might underlie the observed associations. Future studies examining dietary patterns that consider different combinations of food intake may help clarify these associations. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by research grants HD4854, HD52473 and HD57210 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and grant P30 DK046200 from the National Institute of Diabetes and Digestive and Kidney Diseases. The Nurses' Health Study II is supported by the Public Health Service grant UM1 CA176726 from the National Cancer Institute, National Institutes of Health. HRH is supported by the National Cancer Institute, National Institutes of Health (K22 CA193860). No competing interests. n/a.
Many women experience emotional and physical symptoms around the time of ovulation and more so before menstruation interfering with their daily normal life also known as premenstrual syndrome (PMS). Recent observational data suggest that supplementation with Lipogen's phosphatidylserine (PS) and phosphatidic acid (PA) complex (PAS) alleviates these PMS symptoms. The aim of this study was to confirm these observations on the effects of PAS on PMS symptom severity within a controlled clinical trial setting. Forty women aged 18-45 years with a diagnosis of PMS were assigned to either take PAS (containing 400 mg PS & 400 mg PA per day) or a matching placebo. The study comprised 5 on-site visits including 1 baseline menstrual cycle followed by 3 treatment cycles. Treatment intake was controlled for by using an electronic device, the Medication Event Monitoring System (MEMS(®)). Primary outcome of the study was the PMS symptoms severity as assessed by using the Daily Record of Severity of Problems (DRSP). Further, SIPS questionnaire (a German version of the Premenstrual Symptoms Screening Tool (PSST)), salivary hormone levels (cortisol awakening response (CAR) and evening cortisol levels) as well as serum levels (cortisol, estradiol, progesterone and corticosteroid binding globulin (CBG)) were assessed. PMS symptoms as assessed by the DRSP Total score showed a significantly better improvement (p = 0.001) over a 3 cycles PAS intake as compared to placebo. In addition, PAS treated women reported a greater improvement in physical (p = 0.002) and depressive symptoms (p = 0.068). They also reported a lower reduction of productivity (p = 0.052) and a stronger decrease in interference with relationships with others (p = 0.099) compared to the placebo group. No other DRSP scale or item showed significant results. Likewise, the reduction in the number of subjects fulfilling PMS or premenstrual dysphoric disorder (PMDD) criteria as classified by the SIPS did not differ between the PAS and the placebo group. For the biomarkers, the salivary cortisol percentage increase of the CAR was significantly less pronounced in the follicular phase of cycle 4 than in the follicular phase of cycle 1 for subjects taking PAS when compared to subjects taking placebo (p = 0.018). Furthermore, the change of serum cortisol levels between visit 1 and visit 5 differed significantly between groups (p = 0.043). While serum cortisol levels of PAS treated females slightly decreased between visit 1 and visit 5, cortisol levels of females treated with placebo increased. For all other biomarkers, no treatment effects were observed over the 4 cycles study period. Overall, this study confirms that a daily intake of PAS, containing 400 mg PS and 400 mg PA, can be considered as safe. Results substantiate the efficacy of PAS in reducing symptoms of PMS. In view of the recent inclusion of severe PMS symptoms (PMDD) in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), the positive results of this clinical study merits consideration of developing the PAS complex as a botanical drug for treatment of PMDD. The study is registered at Deutsches Register Klinischer Studien with the registration number DRKS00009005.
Reports on clinical uses of platelet-rich plasma (PRP) have dramatically increased in the last decade. Indications for PRP therapy range from muscle and skeletal injuries to hair re-growth. More recently evidences have shown its positive effects in promoting endometrial and follicular growth and gestation in assisted reproduction cycles. We discuss the putative role of PRP on endometrial receptivity, with a brief history of its applications in research and clinical therapies. Despite its widespread uses in medicine, the mechanisms through which PRP exerts its regenerative effects are only postulated, not based on scientific data. There is an unmet need for advanced research to corroborate present findings in the clinical scenario.
Hyperemesis gravidarum (HG), severe nausea and vomiting of pregnancy, occurs in 0.3-2% of pregnancies and is associated with maternal and fetal morbidity. The cause of HG remains unknown, but familial aggregation and results of twin studies suggest that understanding the genetic contribution is essential for comprehending the disease etiology. Here, we conduct a genome-wide association study (GWAS) for binary (HG) and ordinal (severity of nausea and vomiting) phenotypes of pregnancy complications. Two loci, chr19p13.11 and chr4q12, are genome-wide significant (p < 5 × 10-8) in both association scans and are replicated in an independent cohort. The genes implicated at these two loci are GDF15 and IGFBP7 respectively, both known to be involved in placentation, appetite, and cachexia. While proving the casual roles of GDF15 and IGFBP7 in nausea and vomiting of pregnancy requires further study, this GWAS provides insights into the genetic risk factors contributing to the disease.
Contraception/ComparisonDepression and MoodMental Health OutcomesContraceptive Safety
We performed a systematic review to look for an association between progestin-only contraception and depression. We searched PubMed, Ovid and Web of Science for English-language articles including progestin-only contraception and depression from database inception to September 2016. We evaluated study quality with the procedures guiding reviews for the United States Preventive Services Task Force and the Cochrane Risk of Bias Tools. We included studies that evaluated progestin-only contraception and depression, focusing on externally validated depression measures. We excluded case studies, review articles and other psychiatric disorders. We identified 26 studies that met the inclusion criteria, including 5 randomized controlled trials, 11 cohort studies and 10 cross-sectional studies. We found minimal association between progestin-only methods and depression. No correlation with depression was found in five low-quality, high-risk-of-bias progestin subdermal implant studies and four out of five varying-quality and medium-risk-of-bias levonorgestrel intrauterine device studies. Three medroxyprogesterone acetate intramuscular injection trials with varying levels of quality and bias show no difference in depression. Two progestin-only contraceptive pill studies with varying levels of quality and bias indicate no increase in depression scores, while one good-quality, medium-bias study shows an association between progestin-only pills, the intrauterine device and depression. Despite perceptions in the community of increased depression following the initiation of progestin contraceptives, the preponderance of evidence does not support an association based on validated measures (mostly level II-1 evidence, moderate quality, low risk of bias).
Oliveira MAP et al., 2018·Archives of gynecology and obstetrics
Adenomyosis is defined as the presence of endometrial glands and stroma within the myometrium. The true prevalence is unknown and has been reported to range from 1 to 70%. It has a significantly negative impact on women's quality of life, causing abnormal uterine bleeding, dysmenorrhea, and chronic pelvic pain. The definitive treatment for adenomyosis is hysterectomy, although it does not contemplate patients who wish to preserve their fertility. The aim of this paper is to discuss the latest evidence on the surgical techniques for the treatment of adenomyosis published in medical-scientific databases. A comprehensive literature search for articles published from 1996 to 2017 related to surgery for adenomyosis was made in Pubmed, Medline, the Cochrane Library, and Google Scholar, in English, adenomyosis, surgery, pathogenesis, dysmenorrhea and infertility. There is extensive evidence on several surgical approaches for the improvement of adenomyosis-related symptoms; however, there is no robust evidence that they are effective for infertility. The management of adenomyosis is quite complex and controversial. Complications after extensive uterine reconstruction, such as uterine rupture, should be considered and discussed with the patient. There are still limited data to support surgery effectiveness, especially for infertility, and further well-designed studies are required.
Despite being first described two thousand years ago, the varicocele remains a controversial multifaceted disease process with numerous biological consequences including infertility, hypogonadism, and chronic orchidalgia. The underlying mechanisms remain poorly understood and likely include hypoxia, oxidative stress, hyperthermia, anatomical aberrations, and genetics as primary components. Despite a high prevalence amongst asymptomatic fertile men, varicoceles paradoxically also represent the most common correctable cause for male infertility. In this systematic review we discuss the rich historical aspects of the varicocele and the contemporary data regarding its clinical manifestations. We performed a systematic literature review with the goal of comparing outcomes and complication rates of each of the major surgical approaches as they relate to infertility and pain. We performed a Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA)-compliant systematic literature review for manuscripts focused on varicocele and its biological consequences. We identified 112 studies suitable for qualitative analysis and included 56 of these for quantitative analysis, with an emphasis on infertility and chronic pain outcomes. Taken together, the clinical work to date suggests that the highest fertility rates and the lowest complication rates are associated with the microsurgical subinguinal surgical approach to varicocelectomy. In all, 26-40% of patients undergoing varicocelectomy will successfully achieve short-term spontaneous pregnancy, and up to 90% of all patients undergoing varicocelectomy for pain will have improvement and/or resolution of their symptoms. Taken together, the data support an ongoing role for varicocelectomy in both of these clinical arenas.
Rooney KL et al., 2018·Dialogues in clinical neuroscience
The relationship between stress and infertility has been debated for years. Women with infertility report elevated levels of anxiety and depression, so it is clear that infertility causes stress. What is less clear, however, is whether or not stress causes infertility. The impact of distress on treatment outcome is difficult to investigate for a number of factors, including inaccurate self-report measures and feelings of increased optimism at treatment onset. However, the most recent research has documented the efficacy of psychological interventions in lowering psychological distress as well as being associated with significant increases in pregnancy rates. A cognitive-behavioral group approach may be the most efficient way to achieve both goals. Given the distress levels reported by many infertile women, it is vital to expand the availability of these programs.
Maxwell E et al., 2018·Journal of Obstetrics and Gynaecology Canada
The purpose of this study was to explore how barriers to accessing fertility services affect the treatment decisions made by fertility patients and service providers in Newfoundland and Labrador. Semistructured, in-depth interviews were conducted with 11 patients across Newfoundland and with eight service providers from Newfoundland and Labrador Fertility Services (located in St. John's) to gather the perspectives of both patients and providers. The interview transcripts were analyzed thematically. Patients' responses to fertility service access barriers included choosing cheaper drugs, substituting intrauterine insemination (IUI) for IVF or not using IVF, delaying IVF, choosing more accessible IVF clinics, transferring multiple embryos, and stopping treatment altogether. Some patients, however, noted that the barriers would not stop them from continuing with treatment. Providers' responses to the barriers patients faced included changing drug protocols, manipulating ovulation, providing teleconsultations, and minimizing patients' clinic visits for those living some distance away from St. John's. Both patients and providers make treatment-related decisions to maximize the likelihood of a successful pregnancy and to reduce costs, which can result in less effective care and at times increased risk to the patient. Unlike with other types of care, responses to barriers to fertility treatment largely result in changes to individual patient treatment plans rather than changing models of care. As a result, many patients must continue to seek fertility services in large urban centres and incur substantial personal costs.
Chronic endometritis is a persistent inflammation of the endometrial mucosa caused by bacterial pathogens such as Enterobacteriaceae, Enterococcus, Streptococcus, Staphylococcus, Mycoplasma, and Ureaplasma. Although chronic endometritis can be asymptomatic, it is found in up to 40% of infertile patients and is responsible for repeated implantation failure and recurrent miscarriage. Diagnosis of chronic endometritis is based on hysteroscopy of the uterine cavity, endometrial biopsy with plasma cells being identified histologically, while specific treatment is determined based on microbial culture. However, not all microorganisms implicated are easily or readily culturable needing a turnaround time of up to 1 week. We sought to develop a molecular diagnostic tool for chronic endometritis based on real-time polymerase chain reaction equivalent to using the 3 classic methods together, overcoming the bias of using any of them alone. Endometrial samples from patients assessed for chronic endometritis (n = 113) using at least 1 or several conventional diagnostic methods namely histology, hysteroscopy, and/or microbial culture, were blindly evaluated by real-time polymerase chain reaction for the presence of 9 Chlamydia trachomatis, Enterococcus, Escherichia coli, Gardnerella vaginalis, Klebsiella pneumoniae, Mycoplasma hominis, Neisseria gonorrhoeae, Staphylococcus, and Streptococcus. The sensitivity and specificity of the molecular analysis vs the classic diagnostic techniques were compared in the 65 patients assessed by all 3 recognized classic methods. The molecular method showed concordant results with histological diagnosis in 30 samples (14 double positive and 16 double negative) with a matching accuracy of 46.15%. Concordance of molecular and hysteroscopic diagnosis was observed in 38 samples (37 double positive and 1 double negative), with an accuracy of 58.46%. When the molecular method was compared to microbial culture, concordance was present in 37 samples (22 double positive and 15 double negative), a matching rate of 56.92%. When cases of potential contamination and/or noncultivable bacteria were considered, the accuracy increased to 66.15%. Of these 65 patients, only 27 patients had consistent histological + hysteroscopic diagnosis, revealing 58.64% of nonconcordant results. Only 13 of 65 patients (20%) had consistent histology + hysteroscopy + microbial culture results. In these cases, the molecular microbiology matched in 10 cases showing a diagnostic accuracy of 76.92%. Interestingly, the molecular microbiology confirmed over half of the isolated pathogens and provided additional detection of nonculturable microorganisms. These results were confirmed by the microbiome assessed by next-generation sequencing. In the endometrial samples with concordant histology + hysteroscopy + microbial culture results, the molecular microbiology diagnosis demonstrates 75% sensitivity, 100% specificity, 100% positive and 25% negative predictive values, and 0% false-positive and 25% false-negative rates. The molecular microbiology method describe herein is a fast and inexpensive diagnostic tool that allows for the identification of culturable and nonculturable endometrial pathogens associated with chronic endometritis. The results obtained were similar to all 3 classic diagnostic methods together with a degree of concordance of 76.92% providing an opportunity to improve the clinical management of infertile patients with a risk of experiencing this ghost endometrial pathology.
InfertilityUnited States 2015 National OutcomesCDC ART Reporting SystemMultiple Birth and Preterm Delivery Rates
Open Access
Since the first U.S. infant conceived with assisted reproductive technology (ART) was born in 1981, both the use of ART and the number of fertility clinics providing ART services have increased steadily in the United States. ART includes fertility treatments in which eggs or embryos are handled in the laboratory (i.e., in vitro fertilization [IVF] and related procedures). Although the majority of infants conceived through ART are singletons, women who undergo ART procedures are more likely than women who conceive naturally to deliver multiple-birth infants. Multiple births pose substantial risks for both mothers and infants, including obstetric complications, preterm delivery (<37 weeks), and low birthweight (<2,500 g) infants. This report provides state-specific information for the United States (including the District of Columbia and Puerto Rico) on ART procedures performed in 2015 and compares birth outcomes that occurred in 2015 (resulting from ART procedures performed in 2014 and 2015) with outcomes for all infants born in the United States in 2015. 2015. In 1995, CDC began collecting data on ART procedures performed in fertility clinics in the United States as mandated by the Fertility Clinic Success Rate and Certification Act of 1992 (FCSRCA) (Public Law 102-493 [October 24, 1992]). Data are collected through the National ART Surveillance System, a web-based data collection system developed by CDC. This report includes data from 52 reporting areas (the 50 states, the District of Columbia, and Puerto Rico).
In 2015, a total of 182,111 ART procedures (range: 135 in Alaska to 23,198 in California) with the intent to transfer at least one embryo were performed in 464 U.S. fertility clinics and reported to CDC. These procedures resulted in 59,334 live-birth deliveries (range: 55 in Wyoming to 7,802 in California) and 71,152 infants born (range: 68 in Wyoming to 9,176 in California). Nationally, the number of ART procedures performed per 1 million women of reproductive age (15-44 years), a proxy measure of the ART utilization rate, was 2,832. ART use exceeded the national rate in 13 reporting areas (California, Connecticut, Delaware, the District of Columbia, Hawaii, Illinois, Maryland, Massachusetts, New Hampshire, New Jersey, New York, Rhode Island, and Virginia). Nationally, among ART transfer procedures in patients using fresh embryos from their own eggs, the average number of embryos transferred increased with increasing age of the woman (1.6 among women aged <35 years, 1.8 among women aged 35-37 years, and 2.3 among women aged >37 years). Among women aged <35 years, the national elective single-embryo transfer (eSET) rate was 34.7% (range: 11.3% in Puerto Rico to 88.1% in Delaware). In 2015, ART contributed to 1.7% of all infants born in the United States (range: 0.3% in Puerto Rico to 4.5% in Massachusetts). ART also contributed to 17.0% of all multiple-birth infants, 16.8% of all twin infants, and 22.2% of all triplets and higher-order infants. The percentage of multiple-birth infants was higher among infants conceived with ART (35.3%) than among all infants born in the total birth population (3.4%). Approximately 34.0% of ART-conceived infants were twins and 1.0% were triplets and higher-order infants. Nationally, infants conceived with ART contributed to 5.1% of all low birthweight infants. Among ART-conceived infants, 25.5% had low birthweight, compared with 8.1% among all infants. ART-conceived infants contributed to 5.3% of all preterm (gestational age <37 weeks) infants. The percentage of preterm births was higher among infants conceived with ART (31.2%) than among all infants born in the total birth population (9.7%). Among singletons, the percentage of ART-conceived infants who had low birthweight was 8.7% compared with 6.4% among all infants born. The percentage of ART-conceived infants who were born preterm was 13.4% among singletons compared with 7.9% among all infants. Multiple births from ART contributed to a substantial proportion of all twins, triplets, and higher-order infants born in the United States. For women aged <35 years, who are typically considered good candidates for eSET, the national average of 1.6 embryos was transferred per ART procedure. Of the four states (Illinois, Massachusetts, New Jersey, and Rhode Island) with comprehensive mandated health insurance coverage for ART procedures (i.e., coverage for at least four cycles of IVF), three (Illinois, Massachusetts, and New Jersey) had rates of ART use exceeding 1.5 times the national rate. This type of mandated insurance coverage has been associated with greater use of ART and likely accounts for some of the difference in per capita ART use observed among states. Twins account for the majority of ART-conceived multiple births. Reducing the number of embryos transferred and increasing use of eSET when clinically appropriate could help reduce multiple births and related adverse health consequences for both mothers and infants. State-based surveillance of ART might be useful for monitoring and evaluating maternal and infant health outcomes of ART in states with high ART use.
InfertilityCRP and FecundabilityInflammation-Mediated AnovulationEAGeR Trial Inflammation Analysis
To assess systemic inflammation in relation to fecundability and anovulation.
Prospective cohort study among participants in the Effects of Aspirin in Gestation and Reproduction trial who were assigned to the placebo.
Academic medical centers. PATIENT(S): Healthy eumenorrheic women (n = 572), 18-40 years of age, with one or two pregnancy losses, attempting spontaneous pregnancy. INTERVENTION(S): Baseline serum high-sensitivity C-reactive protein (hsCRP) values <10 mg/L were categorized into tertiles. MAIN OUTCOME MEASURE(S): Discrete Cox proportional hazards models estimated the fecundability odds ratio (FOR) and 95% confidence interval (CI) and adjusted for potential confounders. Log-binomial regression estimated the risk ratio (RR) and 95% CI of anovulation. The algorithm to define anovulation used data on urinary concentrations of hCG, pregnanediol-3-glucuronide, and LH as well as fertility monitor readings. RESULT(S): Higher hsCRP was associated with reduced fecundability but not with an increased risk of anovulation. CONCLUSION(S): Among healthy women attempting pregnancy after one or two pregnancy losses, we found preliminary evidence that systemic inflammation is associated with reduced fecundability, but not independently from adiposity. Sporadic anovulation did not appear to drive this association. Trial ClinicalTrials.gov: NCT00467363.
Contraception/ComparisonBreast Cancer RiskHormonal Contraception AssociationContemporary Contraceptive Safety
Contemporary hormonal contraception formulations contain lower doses of estrogen, have new synthetic progestin components, and provide novel methods of delivery that have not been studied extensively in relation to breast cancer risk. Given that hormonal contraception is the leading method of birth control in the United States, it is important to reevaluate risk using current formulations. Recent studies including contemporary hormonal contraception formulations will be described.
InfertilityOocyte RetrievalProcedural SafetyIVF Procedural Risks
Open Access
The most common complication during oocyte retrieval is vaginal bleeding, which is largely controlled by buffer application. In conclusion, the oocyte retrieval process can be considered a safe procedure.
Fertility AwarenessFertile Window IdentificationPrimary Care Pregnancy AchievementNatural Fertility Indicator Effectiveness
Open Access
To determine the effectiveness of achieving pregnancy with focused intercourse in the fertile window identified using natural fertility indicators. 24-cycle prospective effectiveness study.
A North American web-based fertility monitoring service. 256 North American women aged 20-43 (mean age 29.2 years) seeking to achieve pregnancy. Participants identified their fertile window with either electronic hormonal fertility monitoring or cervical mucus monitoring, or both, and recorded their observations on an online fertility tracking system. Pregnancies were validated by nurses with an online self-assessed pregnancy evaluation form. Survival analysis was used to determine pregnancy rates. There were 150 pregnancies among the 256 participants with an overall pregnancy rate of 78 per 100 women over 12 menstrual cycles. There were 54 pregnancies (68%) among the 80 women using the fertility monitor, 11 pregnancies (46%) among the 24 women using mucus monitoring, and 90 (63%) among the 143 women using both mucus and monitor. The 12-cycle pregnancy rates per 100 women were 83 (monitor group), 72 (mucus group), and 75 (mucus and monitor group). Pregnancy rates reached 100% at 24 cycles of use for those women using the hormonal fertility monitor. Use of the hormonal fertility monitor alone seems to offer the best natural estimate of the fertile phase of the menstrual cycle for women wishing to achieve a pregnancy. Focusing intercourse through 24 menstrual cycles can be beneficial for achieving pregnancy.
PCOSMetformin TherapyTestosterone and LHLong-Term Treatment Outcomes
The long-term effects of metformin in women with polycystic ovarian syndrome (PCOS) are inadequately studied. The effects of metformin on women with PCOS during 24 months with respect to menses, hormones, and metabolic profiles are assessed. Prospective cohort. A reproductive endocrinology clinic in a university-affiliated medical center. One hundred nineteen women with PCOS, defined by the Rotterdam criteria, were enrolled. Metformin was given daily for 24 months. The primary outcome was the proportion of patients with regular menstruation during treatment. Changes in anthropometric, hormonal, and metabolic parameters were also assessed. Analyses were performed using segmented regression analysis with a generalized estimating equation methodology. Outcomes are expressed as magnitude of change from the baseline. Both overweight (OW) and normal-weight (NW) women with PCOS had increased menstrual frequency and decreased body mass index (BMI), testosterone, and luteinizing hormone levels in the first 6 months. Further stratification showed that NW women exhibiting elevated testosterone at baseline had the largest magnitude of improvement at 6 months [odds ratio (OR), 7.21; 95% confidence interval (CI), 2.35 to 22.17], whereas OW patients with normal testosterone were most likely to achieve normal menses at 12 months (OR, 0.63; 95% CI, 0.47 to 0.77). Metformin was associated with improvements in the menstrual cycle and most hormonal profiles in OW and NW women with PCOS during 24 months of treatment. Most parameters reached maximal response and steady-state after 6 months. Phenotypic differences in baseline BMI and testosterone level can be used as patient selection criteria or treatment prognostics.
AndrologyNSAID Effects on Testicular FunctionIbuprofen-Induced HypogonadismIn Vivo/Ex Vivo Testicular Study
Kristensen DM et al., 2018·Proc Natl Acad Sci U S A
Concern has been raised over increased male reproductive disorders in the Western world, and the disruption of male endocrinology has been suggested to play a central role. Several studies have shown that mild analgesics exposure during fetal life is associated with antiandrogenic effects and congenital malformations, but the effects on the adult man remain largely unknown. Through a clinical trial with young men exposed to ibuprofen, we show that the analgesic resulted in the clinical condition named "compensated hypogonadism," a condition prevalent among elderly men and associated with reproductive and physical disorders. In the men, luteinizing hormone (LH) and ibuprofen plasma levels were positively correlated, and the testosterone/LH ratio decreased. Using adult testis explants exposed or not exposed to ibuprofen, we demonstrate that the endocrine capabilities from testicular Leydig and Sertoli cells, including testosterone production, were suppressed through transcriptional repression. This effect was also observed in a human steroidogenic cell line. Our data demonstrate that ibuprofen alters the endocrine system via selective transcriptional repression in the human testes, thereby inducing compensated hypogonadism.
Cote B et al., 2018·International journal of pharmaceutical compounding
Fibromyalgia is a syndrome associated with chronic, widespread musculoskeletal pain, fatigue, depression, and cognitive dysfunction. With few U.S. Food and Drug Administration-approved treatment options, there is evidence that low-dose naltrexone, an opioid antagonist approved for opioid and alcohol dependence at high doses, may have efficacy in the treatment of fibromyalgia and chronic pain. At the doses required for fibromyalgia treatment, naltrexone needs to be compounded, and no data currently exists regarding the long-term stability of low-dose naltrexone capsules. This limits pharmacies to a maximum beyond-use date of 180 days. Our study examined the stability of compounded capsules of low-dose naltrexone in Avicel over 360 days. Naltrexone was extracted from compounded capsules and assessed using reversed-phase high-performance liquid chromatography validated to differentiate between the degraded and undegraded naltrexone. United States Pharmacopeia guidelines state that compounded medications must remain within 10% of the labeled potency at all times during the assigned expiration date for a preparation. Our results show that low-dose naltrexone is stable for 360 days when stored at room temperature and away from light remaining within 90% to 110% of the labeled potency throughout the study period. Based on our study results, the beyond-use date for compounded low-dose naltrexone formulations stored at room temperature and protected from light can be extended to 1 year. The longer beyond-use dating allows patients greater flexibility in using these capsules during the flare-ups associated with fibromyalgia without needing a refill immediately at the onset of symptoms. In addition, it may help compounding pharmacies reduce waste associated with small-batch preparation of these capsules.
The great asymmetry of autoimmune diseases between genders represents one of the most enigmatic observations among the mosaic of autoimmunity. Sex hormones are believed to play a crucial role on this dimorphism. The higher prevalence of autoimmunity among women at childbearing ages, disease onset/relapses during pregnancy, and post-partum are some of the arguments that support this hypothesis. Certainly, motherhood represents one of the most remarkable challenges for the immune system, which not only has to allow for the conceptus, but also has to deal with complex endocrine alterations. Hormonal homeostasis is known to exert a crucial influence in achieving a competent and healthy immune system. Prolactin (PRL) has a bioactive function acting as a hormone and a cytokine. It interferes with immune system modulation, mainly inhibiting the negative selection of autoreactive B lymphocytes. Likewise, hyperprolactinemia has been described in relation to the pathogenesis and activity of several autoimmune disorders. Dopamine is an effective inhibitor of PRL secretion due to either a direct influence on the hypophysis or stimulation of postsynaptic dopamine receptors in the hypothalamus, arousing the release of the PRL inhibitory factor. Hence, dopamine agonists have proven to offer clinical benefits among autoimmune patients and represent a promising therapy to be explored. In this review, we attempt to provide a critical overview of the link between PRL, autoimmune diseases, and motherhood.
Annual summary report on assisted reproductive technology (ART) cycles performed in Japan during 2015, published by the Ethics Committee of the Japan Society of Obstetrics and Gynecology (JSOG).
Chidi-Ogbolu N et al., 2018·Frontiers in physiology
Estrogen has a dramatic effect on musculoskeletal function. Beyond the known relationship between estrogen and bone, it directly affects the structure and function of other musculoskeletal tissues such as muscle, tendon, and ligament. In these other musculoskeletal tissues, estrogen improves muscle mass and strength, and increases the collagen content of connective tissues. However, unlike bone and muscle where estrogen improves function, in tendons and ligaments estrogen decreases stiffness, and this directly affects performance and injury rates. High estrogen levels can decrease power and performance and make women more prone for catastrophic ligament injury. The goal of the current work is to review the research that forms the basis of our understanding how estrogen affects muscle, tendon, and ligament and how hormonal manipulation can be used to optimize performance and promote female participation in an active lifestyle at any age.
Annual report (Jahrbuch) of the Deutsches IVF-Register (DIR) for treatment year 2017. 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).
Fibromyalgia is a poorly understood, chronically disabling pain syndrome. While research has focused on its clinical presentation and treatment, less is known about fibromyalgia's clinical epidemiology in real-world healthcare systems. Gender differences have been difficult to study because relatively few males are diagnosed with fibromyalgia. Veterans Health Administration (VHA) patients diagnosed with fibromyalgia nationwide in FY 2012 were compared to Veterans with other pain diagnoses on sociodemographic characteristics, medical and psychiatric diagnoses, health service use, and opioid and psychotropic prescription fills. Additional analyses compared characteristics of men and women diagnosed with fibromyalgia. Risk ratios and Cohen's
d
were used for bivariate comparisons, followed by logistic regression analyses to identify independent factors associated with a diagnosis of fibromyalgia in the VHA. Altogether, 77,087 of 2,216,621 Veterans with pain diagnoses (3.48%) were diagnosed with fibromyalgia. They were more likely to be female, younger than patients with other pain conditions, more likely to have multiple psychiatric comorbidities and other types of pain, and used more medical outpatient services. Women diagnosed with fibromyalgia were younger and more likely to have headaches, connective tissue diseases (CTD), and psychiatric comorbidities, while men had more comorbid medical conditions. In this large, predominantly older male sample of Veterans with pain diagnoses, those with fibromyalgia were far more likely to be women. Gender comparisons showed women with fibromyalgia were more likely to be diagnosed with psychiatric disorders and CTD, while males were more likely to be diagnosed with medical conditions. Fibromyalgia shows a striking, gender-dependent picture of multimorbidity, which should be considered in treatment.
Gonzales SK et al., 2018·Journal of minimally invasive gynecology
The objective of this study is to report our center's series of robotic-assisted laparoscopic abdominal cerclage (RALAC) placement during pregnancy. Descriptive study (Canadian Task Force classification III). Single academic institution. Patients undergoing RALAC placement during pregnancy. Eleven patients underwent RALAC. Nine out of 11 (81.8%) primary RALAC procedures resulted in a viable live-born neonate; 8 (72.7%) were born at >34 weeks of gestation. Three patients (27.3%) had preterm premature rupture of membranes on postoperative day one, 2 of whom subsequently underwent a dilation and curettage, and 1 patient carried the pregnancy to 29 weeks and delivered a live-born neonate. Four patients had subsequent pregnancies after placement of a RALAC in the antepartum period, all of whom carried successfully beyond 36 weeks, for a total of 16 pregnancies. Fourteen pregnancies (87.5%) resulted in a live birth, and 13 pregnancies (81.3%) were delivered beyond 34 weeks. RALAC is a minimally invasive procedure with an acceptable risk profile and comparable efficacy to traditional open abdominal cerclage. RALAC may be considered an acceptable alternative to open abdominal cerclage in pregnancy, and may be a particularly favorable option in certain settings.
The objective was to examine levels of, correlates of and changes in the use of individual and grouped methods of contraception among US females aged 15-44 from 2008 to 2014. Using three rounds of the National Survey of Family Growth, we analyzed samples of 12,279 (2008), 5601 (2012) and 5699 (2014) females. We conducted simple and multivariable logistic regression analyses to identify associations between demographic characteristics and contraceptive use, as well as between characteristics and changes in use patterns. In terms of overall trends in contraceptive use between 2008 and 2014, there was no significant change in the proportion of women who used a method among either all women (60%) or those at risk of unintended pregnancy (90%). Significant changes in use occurred among six methods. The largest increase in use was among users of long-acting reversible contraceptive (LARC) methods, including the intrauterine device and implant - from 6% to 14% - across almost all population groups of female contraceptive users, while the largest decrease occurred among users of sterilization - from 37% to 28% - with lower-income women driving the decline in female sterilization and higher-income women driving the decline in a partner's sterilization as a primary method. Moderate increases were seen in the use of withdrawal and natural family planning. Most shifts in recent contraceptive use have occurred among the most effective methods - sterilization and LARCs. Differences in method-specific user characteristics underscore the importance of ensuring full access to the broad range of methods available. The lack of change in the overall use of contraceptives among women at risk for unintended pregnancy may have implications for the extent to which further declines in national rates of unintended pregnancy can be expected.
Levine H et al., 2018·Basic and clinical andrology
On the occasion of the XIIIth International Symposium on Spermatology held from 9 to 13 May 2018 in Stockholm (Sweden), participants (guest speakers and audience) collectively felt the need to make a public statement on the general issue of male reproductive health. Our intention is to raise awareness of what we believe is a neglected area of research despite alarming situations around the world. The disclosure strategy desired by the co-authors is to bring it to the attention of the greatest number partly by considering co-publication in the various periodicals dealing with Reproductive Biology and Andrology. BaCA's editorial office accepted this mission and found it natural that our periodical, the official journal of the French Andrology Society (SALF), should carry this message.
InfertilityNational StatisticsIVF Trends and OutcomesNational Fertility Reports
Canadian Fertility and Andrology Society; BORN Ontario, 2018·CFAS / BORN Ontario
CARTR Plus annual report. Presented at the Canadian Fertility and Andrology Society Annual Meeting in September 2017, reporting Canadian ART cycle outcomes.
Chaudhari AP et al., 2018·Indian journal of psychological medicine
Polycystic ovarian syndrome (PCOS) is the most common endocrine disorder among women of reproductive age. Symptoms include amenorrhea, hirsutism, infertility, obesity, acne vulgaris, and androgenic alopecia. PCOS is a stigmatizing condition that affects a woman's identity, mental health and quality of life (QOL). This aspect has not received adequate attention in India. (1) To study the prevalence of anxiety and depression among women suffering from PCOS (2) To determine if symptoms of PCOS were associated with psychiatric morbidity, and (3) To determine the impact of psychiatric morbidity on the QOL. Seventy females in the reproductive age group (18-45 years) diagnosed with PCOS as per Rotterdam criteria and without any preexisting psychiatric illness were clinically interviewed for anxiety and depressive disorders which were then rated according to the Hamilton scales. QOL was assessed using the World Health Organization-QOL-BREF. Binary logistic regression was performed to study the association of the symptoms with the psychiatric morbidity. QOL scores of patients with and without psychiatric morbidity were compared using Mann-Whitney U-test. The prevalence of anxiety and depression in our sample was 38.6% and 25.7%, respectively. Infertility and alopecia were associated with anxiety, while acne was associated with depression. Hirsutism was associated with a lower psychological QOL. Patients with psychiatric morbidity had a significantly lower QOL than those without.
Orouji Jokar T et al., 2017·J Clin Endocrinol Metab
Unexplained infertility (UI), defined as the inability to conceive after 12 months of unprotected intercourse with no diagnosed cause, affects 10% to 30% of infertile couples. An improved understanding of the mechanisms underlying UI could lead to less invasive and less costly treatment strategies. Abnormalities in thyroid function and hyperprolactinemia are well-known causes of infertility, but whether thyrotropin (TSH) and prolactin levels within the normal range are associated with UI is unknown. To compare TSH and prolactin levels in women with UI and women with a normal fertility evaluation except for an azoospermic or severely oligospermic male partner. DESIGN, SETTING, Cross-sectional study including women evaluated at a large academic health system between 1 January 2000 and 31 December 2012 with normal TSH (levels within the normal range of the assay and ≤5 mIU/L) and normal prolactin levels (≤20 ng/mL) and either UI (n = 187) or no other cause of infertility other than an azoospermic or severely oligospermic partner (n = 52). TSH and prolactin. Women with UI had significantly higher TSH levels than controls [UI: TSH 1.95 mIU/L, (1.54, 2.61); TSH 1.66 mIU/L, (1.25, 2.17); P = 0.003]. This finding remained significant after we controlled for age, body mass index, and smoking status. Nearly twice as many women with UI (26.9%) had a TSH ≥2.5 mIU/L compared with controls (13.5%; P < 0.05). Prolactin levels did not differ between the groups. Women with UI have higher TSH levels compared with a control population. More studies are necessary to determine whether treatment of high-normal TSH levels decreases time to conception in couples with UI.
Body LiteracyWomen's Lifespan HealthHealth Indicator Beyond FertilityLifespan Hormonal Health
The concept of the ovarian continuum can be understood as a process that occurs during a woman's lifetime and begins during intrauterine life with fertilization. Women start their reproductive years with approximately five hundred thousand follicles containing oocytes, of which only around five hundred will be released during ovulation. Ovulation has been recognized as an event linked with reproduction; however, recent evidence supports the role of ovulation as a sign of health. The use of biomarkers that help women recognize ovulation enables them to identify their health status. This knowledge helps medical healthcare providers in the prevention, diagnosis, and treatment of different pathologies related with endocrine disorders, gynecological abnormalities, autoimmune, genetic, and neoplastic diseases, as well as pregnancy-related issues. The knowledge of the ovarian continuum and the use of biomarkers to recognize ovulation should be considered a powerful tool for women and medical professionals.
The ovarian continuum is a process that occurs during a woman's lifetime. It begins during intrauterine life with fertilization and ends with menopause. This process can be greatly affected by different conditions such as changes in hormonal levels and illnesses. Therefore, understanding and promoting the knowledge and use of biomarkers of ovulation in women is a key aspect to consider when evaluating their health status. The knowledge and education about the ovarian continuum should be taken into account as a powerful tool for women and medical professionals.
Contraception/ComparisonBreast Cancer RiskCombined Oral ContraceptivesProgestin-Only Methods
Little is known about whether contemporary hormonal contraception is associated with an increased risk of breast cancer. We assessed associations between the use of hormonal contraception and the risk of invasive breast cancer in a nationwide prospective cohort study involving all women in Denmark between 15 and 49 years of age who had not had cancer or venous thromboembolism and who had not received treatment for infertility. Nationwide registries provided individually updated information about the use of hormonal contraception, breast-cancer diagnoses, and potential confounders. Among 1.8 million women who were followed on average for 10.9 years (a total of 19.6 million person-years), 11,517 cases of breast cancer occurred. As compared with women who had never used hormonal contraception, the relative risk of breast cancer among all current and recent users of hormonal contraception was 1.20 (95% confidence interval [CI], 1.14 to 1.26). This risk increased from 1.09 (95% CI, 0.96 to 1.23) with less than 1 year of use to 1.38 (95% CI, 1.26 to 1.51) with more than 10 years of use (P=0.002). After discontinuation of hormonal contraception, the risk of breast cancer was still higher among the women who had used hormonal contraceptives for 5 years or more than among women who had not used hormonal contraceptives. Risk estimates associated with current or recent use of various oral combination (estrogen-progestin) contraceptives varied between 1.0 and 1.6. Women who currently or recently used the progestin-only intrauterine system also had a higher risk of breast cancer than women who had never used hormonal contraceptives (relative risk, 1.21; 95% CI, 1.11 to 1.33). The overall absolute increase in breast cancers diagnosed among current and recent users of any hormonal contraceptive was 13 (95% CI, 10 to 16) per 100,000 person-years, or approximately 1 extra breast cancer for every 7690 women using hormonal contraception for 1 year. The risk of breast cancer was higher among women who currently or recently used contemporary hormonal contraceptives than among women who had never used hormonal contraceptives, and this risk increased with longer durations of use; however, absolute increases in risk were small. (Funded by the Novo Nordisk Foundation.).
Sundermann AC et al., 2017·Obstetrics and gynecology
To assess whether interpregnancy interval length after a pregnancy loss is associated with risk of repeat miscarriage. This analysis includes pregnant women participating in the Right From the Start (2000-2012) community-based prospective cohort study whose most recent pregnancy before enrollment ended in miscarriage. Interpregnancy interval was defined as the time between a prior miscarriage and the last menstrual period of the study pregnancy. Miscarriage was defined as pregnancy loss before 20 weeks of gestation. Cox proportional hazard models were used to estimate crude and adjusted hazard ratios and 95% CIs for the association between different interpregnancy interval lengths and miscarriage in the study pregnancy. Adjusted models included maternal age, race, parity, body mass index, and education. Among the 514 study participants who reported miscarriage as their most recent pregnancy outcome, 15.7% had a repeat miscarriage in the study pregnancy (n=81). Median maternal age was 30 years (interquartile range 27-34) and 55.6% of participants had at least one previous livebirth (n=286). When compared with women with interpregnancy intervals of 6-18 months (n=136), women with intervals of less than 3 months (n=124) had the lowest risk of repeat miscarriage (7.3% compared with 22.1%; adjusted hazard ratio 0.33, 95% CI 0.16-0.71). Neither maternal race nor parity modified the association. Attempting to conceive immediately was not associated with increased risk of miscarriage in the next pregnancy. An interpregnancy interval after pregnancy loss of less than 3 months is associated with the lowest risk of subsequent miscarriage. This implies counseling women to delay conception to reduce risk of miscarriage may not be warranted.
To study the perinatal outcomes between singleton live births achieved with the use of commissioned versus spontaneously conceived embryos carried by the same gestational surrogate. Retrospective cohort study. Academic in vitro fertilization center. PATIENT(S): Gestational surrogate. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Pregnancy outcome, gestational age at birth, birth weight, perinatal complications. RESULT(S): We identified 124 gestational surrogates who achieved a total of 494 pregnancies. Pregnancy outcomes for surrogate and spontaneous pregnancies were significantly different (P<.001), with surrogate pregnancies more likely 33% vs. 1%. Miscarriage and ectopic rates were similar. Of these pregnancies, there were 352 103 achieved from commissioned embryos and 249 conceived spontaneously. Surrogate births had lower mean gestational age at delivery (38.8 ± 2.1 vs. 39.7 ± 1.4), higher rates of preterm birth (10.7% vs. 3.1%), and higher rates of low birth weight (7.8% vs. 2.4%). Neonates from surrogacy had birth weights that were, on average, 105 g lower. Surrogate births had significantly higher obstetrical complications, including gestational diabetes, hypertension, use of amniocentesis, placenta previa, antibiotic requirement during labor, and cesarean section. CONCLUSION(S): Neonates born from commissioned embryos and carried by gestational surrogates have increased adverse perinatal outcomes, including preterm birth, low birth weight, hypertension, maternal gestational diabetes, and placenta previa, compared with singletons conceived spontaneously and carried by the same woman. Our data suggest that assisted reproductive procedures may potentially affect embryo quality and that its negative impact can not be overcome even with a proven healthy uterine environment.