Higher Pregnancy Rates Research Articles

A paradigm of higher success rate of intracytoplasmic sperm injection - preovulatory human chorionic gonadotropin-day serum oestradiol.

The aim of the study is to evaluate the correlation between the level of serum oestradiol (E2) on the day of human chorionic gonadotropin (hCG-day) administration and successful intracytoplasmic sperm injection (ICSI) outcome. This prospective study was performed during the period from January 2019 to September 2021, at Zagazig Obstetrics and Gynecology Department, and Al-Azhar Obstetrics and Gynecology Department, and private ART centers. One hundred and fifty women attending the infertility clinic for ICSI cycles. All women were divided into 5 groups according to the serum E2 level on the day of hCG administration: Group A - serum E2 < 1000 pg/ml; Group B - serum E2 1000 to < 2000 pg/ml; Group C - serum E2 2000 to < 3000 pg/ml;Group D - serum E2 3000 to < 4000 pg/ml; Group E - serum E2 ≥ 4000 pg/ml. The highest fertilization rate (58.1%) was among women with E2 ≥ 4000 pg/ml, while the lowest (37%) was in women with E2 1000 to < 2000 pg/ml. Also, the highest pregnancy rate (21.5%) was among women with E2 > 4000 pg/ml, while the lowest (5.3%) was in women with E2 < 1000 pg/ml. In the current study the median serum E2 level on the day of hCG administration was highly significant in women who became pregnant when compared to women who did not. The best cut-off value of serum E2 at hCG administration was ≥ 3682.3 pg/ml. this study suggests that the optimal range of E2 level for achieving a successful pregnancy is > 4000 pg/ml.

Time line in IVF laboratory

The time line in IVF is critical, as the procedures are associated with the time of the ovulation trigger for follicular maturation, followed by sequential procedures in relation to it. Starting from oocyte recovery scheduled 36 hours post-trigger, the laboratory procedures are followed up sequentially. Oocyte cumulus complex (OCC) may be incubated until insemination or ICSI until 40 hours post-trigger. Conventional insemination may be done either short (4–6 hours) or long insemination (overnight). However, short insemination is associated with an increase in the 3-PN rate. OCC for ICSI may be denuded at least after 38 hours post-trigger, and ICSI may be performed within 2 to 4 hours post-denuding. ICSI done within 2 hours post-denuding appears to be yielding better-quality embryos. Time-lapse studies have indicated that it is possible to obtain higher clinical and live birth rates with embryos reaching the blastocyst stage faster than other embryos. Embryo transfers done with Day 3 embryos result in a higher pregnancy rate than Day 2 while blastocyst transfers perform better than day 3 transfers. Mobilization of patients after ET may not affect the outcome.

Endoscopic Tubal Restorative Surgeries for Tubal Factor Infertility at a Teaching Hospital in North Central Nigeria: A Preliminary Report of a Prospective Longitudinal Study

Abstract Background: Tubal surgery is an acceptable treatment option for infertility due to tubal factors. However, in the era of assisted reproductive technology, the use of restorative tubal surgery for the treatment of tubal factor infertility has been reduced. Objectives: This study was conducted to determine the incidence of endoscopic tubal surgery, tubal factor infertility, fertility outcomes, and factors that influence successful or favorable outcomes among women with gynecological endoscopic surgeries for tubal factor infertility. Materials and Methods: This is a preliminary report of a prospective longitudinal study of women with endoscopic tubal restorative surgery for tubal factor infertility at a Federal Teaching Hospital in North Central Nigeria between November 9, 2016, and February 12, 2020. Thirty-four women aged 26–42 years who had bilateral tubal blockage before surgeries were analyzed. The primary outcome measure was clinical pregnancy, whereas secondary outcomes were tubal patency, live birth, miscarriage, and ectopic pregnancy rates. Data were analyzed using Statistical Package for the Social Sciences version 26. Data analysis was descriptive and inferential at a 95% confidence interval, P &lt; 0.05 was considered statistically significant. Logistic regression was carried out to determine independent factors for successful fertility outcomes after endoscopic tubal surgery. Results: There were 1534 gynecological admissions among whom 159 (10.4%) had endoscopy surgeries for infertility. Of the 159 women, 37 (23.3%) had confirmed tubal infertility with bilateral tubal blockage on hysterosalpingography and laparoscopy with a dye test. Thirty-four (women who met the inclusion criteria were analyzed and three women who had salpingectomy and bilateral tubal disconnection and those with AMH of &lt;1.0ng/mL were excluded from the study. The mean age was 34.0 ± 5.2 years, and the majority (67.6%) were nulliparous. Peritubal adhesions were the most common tubal pathology seen on laparoscopy. Hysteroscopic tubal cannulation with selective salpingography (41%), salpingolysis (29%), salpingostomy (21%), and fimbrioplasty (9%) were the interventions performed. Bilateral and unilateral tubal patencies were achieved in 58.8% and 32.5%, respectively. The overall cumulative clinical pregnancy rate was 38.2%, out of which 35.3% conceived spontaneously. Live births (LBs) and miscarriage rates are 20.6% and 17.6%, respectively. There was no ectopic pregnancy. Regression estimates showed that lower age (P = 0.029), lesser duration of infertility (P = 0.038), and treatment of other etiological factors at the same setting (P = 0.019) are independent factors for successful fertility outcome after endoscopic restorative tubal surgery. Conclusions: The high rate of spontaneous intrauterine pregnancy and LBs in this study rekindles the hope of natural conception at a low cost among women with tubal factor infertility.

A refugee mother's perspective: Healthcare satisfaction and access to health services as an immigrant in Turkiye.

The civil war that broke out in Syria in 2011 caused 3.7 million Syrians to migrate to Turkiye. Being particularly vulnerable women refugees may experience problems with access to healthcare services. This study aimed to determine the health problems of refugees in Ankara, their access to and use of these services. Healthcare-related levels of refugee mothers were assessed using a questionnaire and the study was conducted with the participation of 310 refugee mothers who presented to the Refugee Health Center, between 15 September 2017 and 15 December 2018. Among the participants, 28.4% were minors who were between the ages of 15 and 18 years. The mean age of the mothers was 31.18±13.84 years, while the mean age of the fathers was 32.37±10.76 years. During their residence in Ankara, the participants preferred Refugee Health Centers (94%) and State Hospitals (83%) for healthcare. Of the participants, 42.1% stated that one or more family members had health problems, which necessitated regular hospital visits. In this study, 95.2% of participants stated that they were satisfied with the healthcare services they were receiving. Although state hospitals were frequently used, refugees were also able to find solutions to their health problems through Refugee Health Centers. Nevertheless, while using other healthcare institutions, the biggest issue for the refugees was the language barrier. The high rates of adolescent pregnancy, disabilities, and chronic diseases were found to be among the main health problems of refugees. Women refugees seemed disadvantaged in education, language, income and employment.

Participant experiences with a multipurpose vaginal ring for HIV and pregnancy prevention during a phase 1 clinical trial: learning from users to improve acceptability.

With high concurrent global rates of HIV incidence and unintended pregnancy, there is a need to provide options beyond condoms to enable users to simultaneously prevent HIV acquisition and pregnancy. Multiple vaginal rings are in development as "MPTs" (multipurpose prevention technologies) as they are shown to provide several co-occurring benefits such as discretion, convenience, reversibility and user control. In this Phase 1 trial of a 3-month MPT ring in the U.S., 25 participants (low-risk for HIV and pregnancy) were randomized to use the study ring for 90 days continuously or in 28-day cycles with 2-day removal periods in between. All participants completed in-depth interviews at the end of their study participation. Overall, the ring was well tolerated. Participants resoundingly endorsed the concept of an extended-use, dual-purpose vaginal ring, but reported too many functional challenges and side effects to endorse this particular ring. Participants assigned to the continuous regimen reported more positive experiences with ring use than those in the cyclic group. A minority of participants who experienced minimal side effects and did not experience challenges with vaginal retention of the ring found it appealing. However, the majority of participants experienced challenges (ring slippage, expulsions, side effects, vaginal bleeding changes) with product use that outweighed the potential benefits and led them to report that - in the future - they would not be interested in using this specific version of the ring in its current form. A subset expressed interest in using the current MPT ring under certain conditions (e.g., if fewer expulsions, less bleeding, higher risk for HIV/pregnancy). User feedback regarding participant experiences and challenges with the study ring was continuously shared with the product developer, underscoring the value of early-stage end-user feedback in product development.

Determinants of adolescent sexual behaviour in indonesia during the COVID-19 pandemic: A scoping review.

A high pre-marital sexual behaviour with a correspondingly high pregnancy rate was observed amongst teenagers in Indonesia during the COVID-19 pandemic. This phenomenon was caused by several factors which include, a decrease in the utilization of reproductive health services, inadequate information on appropriate sexual behaviour before marriage, work from home and the Pembelajaran Jarak Jauh/ distance learning policies which increased the use of internet and exposure to pornography. This study aimed to identify the determinant factors associated with adolescent pre-marital sexual behaviour in Indonesia during the COVID-19 pandemic. The method involved the use of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews by searching for relevant articles through ScienceDirect, Google Scholar, PubMed and Garuda (Garba Rujukan Digital) Portal. Twenty-one (21) articles were analysed in this study. The results showed that knowledge about reproductive health, or more specifically pre-marital sexual behaviour, was related to pre-marital sexual behaviour during the COVID-19 pandemic. In addition, attitudes, communication media, peers and family were also related to adolescent pre-marital sexual behaviour during the COVID-19 pandemic. In conclusion, it is necessary to prevent pre-marital sexual behaviour through health promotion to improve adolescent knowledge and attitudes, use of the latest communication media and increase in the role of peer educators and parents.

Assessment of knowledge towards emergency contraceptives among college students in Ramechhap district of Nepal

Introduction: A high rate of unintended pregnancy exists among college students as they belong to the sexually active age group. So, it is significant to know the knowledge of college students regarding emergency contraceptives.&#x0D; &#x0D; Objectives: To assess the knowledge of students towards Emergency Contraceptives and to identify the association between male and female students towards knowledge of emergency contraceptives.&#x0D; &#x0D; Method: An online survey in Ramechhap district among college students studying in bachelor’s and master’s level was conducted from March 15, 2022 to April 10, 2022 where total of 169 students participated. Non parametric test was used to find the result of the objectives.&#x0D; &#x0D; Result: The study showed that 83.4% students had the knowledge of Emergency Contraceptive pills and 59.2% of students first heard about such pills in the last 5 Years. Among them 79.9% of students knew where to get Emergency Contraceptive pills, 24.2% of students know the Emergency Contraceptive pills works if there is menstrual delay. Only 56.9% of students know the time to take Emergency Contraceptives pills after unprotected sexual intercourse and 46.7% of students know that the Emergency Contraceptive pill is not used for regular contraception. Only 49.1% of students know the right number of tablets that needs to be consumed after unprotected intercourse.&#x0D; &#x0D; Conclusion: Majority of the students are aware of the Emergency Contraceptive pills however they have limited understanding about it. In comparison to female students, male had better understanding about Emergency Contraceptives.

Adolescent Girls’ Experiences Regarding Teenage Pregnancy in the Rural Villages of Limpopo Province, South Africa

Every year, 7.3 million girls become pregnant before they turn 18. Teenage pregnancy increases when girls are denied the right to make decisions about their sexual health and well-being, which is a gender equality issue. Among the challenges of gender equality are those expectations that communities have about girls and early motherhood, sexual violence, and rape. Another challenge is the early marriages of children to older men coupled with the unique risks faced by these girls during pregnancy, for example, the interruption of their education, health risks, such as HIV, premature birth, and increased maternal mortality, denying the girls the right to live a healthy life. This study sought to explore the experiences of adolescent girls regarding teenage pregnancy in the rural villages of the Mopani District, Limpopo. A descriptive, explorative, and qualitative design was followed to collect data from 20 pregnant teenagers in a 13–19 years-old age group. A nonprobability purposive sampling method was used to select the participants from the three villages of the Mopani District. The data were collected using an in-depth individual interview. Tesch’s eight steps of data analysis were also applied. The study findings reveal several factors that explain the high rates of teenage pregnancy in rural Limpopo. Among these are the socioeconomic and cultural factors that predispose teens to pregnancy. The consequences of teenage pregnancy were expressed in terms of regret and ill health.

HTLV-1/2 in Indigenous Peoples of the Brazilian Amazon: Seroprevalence, Molecular Characterization and Sociobehavioral Factors Related to Risk of Infection.

HTLV-1/2 infection is endemic in Indigenous peoples of the Americas. Its origin is attributed to the migratory flow of Amerindian ancestral peoples. The present study aimed to investigate the seroprevalence of HTLV-1/2 infection in Indigenous peoples of the Brazilian Amazon. A total of 3350 Indigenous people belonging to 15 communities were investigated. The investigation was performed using serological (ELISA), molecular (qPCR) and confirmatory (Western blot and/or Inno-Lia) tests to detect and differentiate the infection. The seroprevalence was 8.3% for HTLV-1/2 infection, with 0.1% of individuals seropositive for HTLV-1 and 8.1% for HTLV-2. The prevalence of infection was statistically higher in women (10.1%) than in men (6.5%) (p = 0.0002). This female predominance was observed in all age groups; in females the prevalence was significant from 41 years old (p < 0.0001) and in males from 51 years old (p < 0.0001). Here, we present a prevalence of HTLV-1/2 among Indigenous peoples of the Brazilian Amazon. The endemic infection in these groups must reflect the different epidemiological profiles observed in these peoples, such as sexual transmission through rejection of condom use, breastfeeding, especially in cases of cross-breastfeeding, and the high rate of pregnancy in the villages.

Overcome the Fear (Vencer el Miedo): using entertainment education to impact adolescent sexual and reproductive health and parent-child communication in Mexico

BackgroundAdolescents in Mexico experience high pregnancy and birth rates. A collaboration with Grupo Televisa led to the development of an entertainment-education telenovela intervention, Overcome the Fear (OTF), which aired in 2020 to a national audience and addressed adolescent sexual and reproductive health (SRH) topics. This study details the development and evaluation of OTF’s impact on adolescent contraceptive practices and parent-adolescent SRH communication in Mexico.MethodsWe conducted cross-sectional survey interviews (street-intercept and telephone) with 12–19-year-olds (n = 1640) and parents of adolescent children (n = 820) post-broadcast across Mexico’s five most-populated metropolitan zones. Quotas were implemented for gender, zone, and OTF viewership (viewer vs. non-viewer). Bivariate statistics and multivariable binary logistic regression models assessed the relationship between OTF viewership (including parent-adolescent co-viewing) and adolescent contraceptive practices and parent-adolescent SRH communication. Adolescent and parent data are not dyadic and were analyzed separately.ResultsNearly half of adolescents (47.9%) and parents (47.7%) were viewers. Among adolescents, bivariate analyses suggest that viewers had less negative attitudes towards contraception (p < .001). Logistic regression models suggest that adolescent viewers were more likely to seek out information about contraception (p < .001) and unhealthy romantic relationships (p = .019), and to use contraception other than condoms (p = .027) and dual contraception (p = .042) in the last 3 months. Among parents, bivariate analyses suggest that non-viewers had more positive attitudes towards abstinence (p = .045) and more negative attitudes towards contraception and communication with adolescents about sex (p = .001). Logistic regression models suggest that parent viewers were more likely to have talked with adolescent children about sexual relations (p < .001), contraceptive methods (p = .01), condoms (p = .002), and abstinence (p = .002) in the last 3 months. Parent-adolescent co-viewing of OTF was also significantly related to certain outcomes in bivariate analyses.ConclusionsThis study suggests that viewership of a high-quality entertainment-education telenovela informed by extensive formative research is related to adolescent health outcomes and to parent-adolescent SRH communication on a country-wide scale in Mexico. Entertainment-education remains an underutilized public health strategy, despite its promise to engage viewers and motivate healthful behaviors.

Effect of High-Dose Cabergoline Therapy for Hyperprolactinemic Infertility among Bangladeshi Women

Background: Cabergoline is effective in the treatment of hyperprolactinemic hypogonadism. It is a highly effective and long-acting inhibitor of prolactin secretion. The rate of cabergoline-induced pregnancy in women with prolactinoma, is unknown. Objective: The aim of present study is to evaluate the efficacy and safety of high-dose cabergoline therapy for hyperprolactinemic infertility among Bangladeshi women. Method: This descriptive cross- sectional study was conducted among 50 patients from January, 2020 to January, 2022 in at The Medinova Diagnostic Centre, Sylhet, Bangladesh. Results: In our study, maximum (14) patients belong to the age group of 19 to 23 years, and minimum number of patients (4) was between 39 to 43 years. Maximum (52%) patients had the primary infertility and 48% had secondary infertility. The mean values of thyroid stimulating hormone (TSH), Follicle-stimulating hormone (FSH), luteinizing hormone (LH) and prolactin PRL is 3.93±6.58, 10.96±13.58, 9.83±6.8, and 12.46±14.39 respectively and these were significant. 12% patients had PCO and 88% patients were normal in our study. 78% semens were normal, 4% semen showed Azzospermia, 14% semens showed Oligo Astheno Spine and 4% semens showed Astheno spine. Conclusion: In infertile women with prolactinoma, cabergoline can achieve a high pregnancy rate with uneventful outcomes. The findings demonstrated that cabergoline can be used safely to improve menstrual cycles in hyperprolactinemia.

Fertility Outcomes after Surgical Management of Colorectal Endometriosis: A Single-center Retrospective Study

To assess the pregnancy rate after surgery for colorectal endometriosis. A retrospective, single-centre study performed from January 2014 to December 2019. A university tertiary referral centre. Patients with the intention to get pregnant under the age of 43 years, with or without a history of infertility and who were surgically managed for colorectal endometriosis. Complete excision of deeply infiltrating endometriosis (DIE). The postoperative pregnancy rate was assessed. Seventy-seven patients had surgery; their mean age was 32.5 ± 4.4 years. Preoperative documented infertility was present in 77.9% (n = 60) of patients. The mean length of history of infertility was 36.2 ± 24.9 months. The procedure was performed by laparoscopic surgery in 92.2% (n = 71) of patients. Non-conservative, conservative and mixed treatment were performed in 66.2% (n = 51), 29.9% (n = 23) and 3.9% (n = 3) of patients, respectively. According to the Clavien-Dindo classification, the 3B complication rate was 6.5% (n = 5). The mean follow-up was 46.7 ± 20.6 months. Clinical pregnancies were defined by the presence of intra-uterine pregnancy with an embryo with cardiac activity. The postoperative pregnancy rate was 62.3% (n = 48), and 54.2% (n = 26) were spontaneous. The mean number of pregnancies was 1.2 ± 0.4 per patient. In addition, 18.7% (n = 9) of patients got pregnant twice. The mean time from surgery to pregnancy was 13.8 ± 13.1 months. The live birth rate was 89.1% (n = 41). There were no significant differences concerning the prognostic criteria reported in the literature (anti-Müllerian hormone level, age, presence of adenomyosis). There were no predictive criteria for live births. According to this study, surgery for colorectal endometriosis results in a high postoperative pregnancy rate. Studies with a high level of evidence are needed to determine good candidates for this type of surgery.

Effectiveness, complications, and reproductive outcomes after cesarean scar pregnancy management: a retrospective cohort study

There is a dramatic rise in cesarean deliveries worldwide, leading to higher complication rates in subsequent pregnancies. One of these complications is a cesarean scar pregnancy. During the last decades, treatment options for cesarean scar pregnancies have changed, and less invasive interventions have been employed to preserve fertility and reduce morbidity. However, the optimal treatment approach and the influence of various treatments on reproductive outcomes have to be determined. This study aimed to evaluate the short- and long-term outcomes after cesarean scar pregnancy management. We conducted a retrospective cohort study of women determined to have a cesarean scar pregnancy from 2010 to 2021 at a tertiary referral center, the Amsterdam University Medical Center, in the Netherlands. Outcomes of the following management strategies were compared: expectant management, methotrexate, curettage with temporary cervical cerclage, or a laparoscopic niche resection. We performed a curettage if the cesarean scar pregnancy did not cross the serosal line of the uterus, and a laparoscopic niche resection was performed if the cesarean scar pregnancy crossed the serosal line. The main outcomes were treatment efficacy and time to subsequent ongoing pregnancy or pregnancy leading to a live birth. Of the 60 included women, 5 (8.3%) were managed expectantly, 8 (13.3%) were treated with methotrexate, 31 (51.8%) were treated with a curettage, and 16 (26.7%) with a laparoscopic niche resection. The groups were not comparable. The gestational age and human chorionic gonadotropin levels were generally higher in women who received methotrexate or a laparoscopic niche resection. Additional treatment in the conservative group was needed for 4 (80%) women after expectant management and for 7 (87.5%) women after methotrexate treatment. In the surgical group, all 31 women treated with a curettage and all 16 treated with a laparoscopic niche resection did not require additional treatment. The subsequent ongoing pregnancy rate after cesarean scar pregnancy management was 81.1% (30/37) among women who wished to conceive, with a live birth rate of 78.4% (29/37); 1 woman was in her third trimester of pregnancy at the time of analyses. The time between cesarean scar pregnancy management and subsequent ongoing pregnancy was 4 months (interquartile range, 3-6; P=.02) after expectant management, 18 months (interquartile range, 13-22) after initial methotrexate treatment, 5 months (interquartile range, 3-14; P=.01) after a curettage, and 6 months (interquartile range, 4-15; P=.03) after a laparoscopic niche resection. Surgical treatment of a cesarean scar pregnancy led to a high success rate without additional interventions, high pregnancy rates with a short time interval between treatment, and subsequent pregnancy leading to an ongoing pregnancy or live birth. Conservative management, both with expectant management and methotrexate treatment, led to high (re)intervention rates. Different management approaches are indicated for different types of cesarean scar pregnancies.

Computer-assisted assessment of ovarian echotexture parameters in mares following changes after ovulation determined by ultrasonography.

This study was carried out to determine the time-dependent changes in the ultrasonographic image of the ovary with computer-assisted analysis programs at certain intervals after ovulation and to determine whether computer-assisted analysis programs and ovulation programs can be managed in cases where the ovulation time is unknown. The study included 40 purebred Arab mares. The study was subdivided into 4 different time periods of 6 (Group 1), 12 (Group 2), 18 (Group 3) and 24 (Group 4) hours following ovulation. In addition, after ovulation and ultrasonographic examination, natural insemination was performed at 6, 12, 18 and 24 hours, and pregnancy examination and follow-up were performed at 15-30-45 days. In the echotexture analysis, mean grayness value (MGV) and contrast (CON) measurements were at different levels according to the time groups (p⟨0.001). Homogeneity (HOM) measurements were at different levels according to the time groups (p⟨0.001). A very strong, significant negative correlation was determined between MGV and pregnancy rates (r=-0.91, p=0.01, p⟨0.05). No significant relationship was observed between HOM values and pregnancy rates (r=0.19, p=0.23, p>0.05). A very strong, significant negative correlation was determined between CON and pregnancy rates (r=-0.92, p=0.01, p⟨0.05). It was concluded that the use of ultrasonographic echotexture in mares after ovulation provided very important information. In cases where the time of ovulation was not known, by looking at the values of echotexture parameters, it was seen that the highest pregnancy rates were at the 6th hour and the lowest pregnancy rates were at the 24th hour. As the echotexture parameters MGV and CON increased, it was determined that pregnancy rates decreased, but there was no relationship between them and the HOM value.

Examining Potential Intervention Options in the KwaZulu-Natal Province to Reduce Adolescent Pregnancy in Selected South African schools

In South African communities, adolescent pregnancy has become a larger socioeconomic issue that has reached new heights. Although it may prove problematic in South Africa, it is not exclusive to the country. Studies indicate that this is a global problem. For example, the United States has regularly documented high rates of adolescent pregnancy. This paper’s overarching objective was to determine the frequency of adolescent pregnancy in high schools in South Africa, particularly in the KwaZulu-Natal Province. In addition, the objective was to establish practical solutions for reducing adolescent pregnancy based on the study's findings. Thus, the article focused predominantly on teenage pregnancy and parenthood and its impact on the lives of young people, family structures, cultural and structural violence in South African families and its residual effects on the lives of these young individuals. The researchers used a qualitative research method to collect data via semi-structured interviews. The researchers also employed focus group discussions and narratives. The outcomes of the study indicate that family support, changes in cultural mindset, and encouragement of social responsibility are potential strategies for preventing teen pregnancy.

Oleuropein suppresses endometriosis progression and improves the fertility of mice with endometriosis

BackgroundEndometriosis is an estrogen-dependent inflammatory reproductive disease. Therefore, systematic estrogen depletion and anti-inflammatory drugs are the current treatment for endometriosis. However, current endometriosis treatments have low efficacy and cause adverse effects in endometriosis patients. Consequently, alternative endometriosis treatments targeting endometriosis-specific factors are in demand. In this context, ERβ was selected as a druggable target for endometriosis due to its critical role in progression. Therefore, selective targeting of ERβ without inhibiting ERα activity would be a new paradigm for endometriosis treatment to overcome the low efficacy and adverse effects of hormonal endometriosis therapy.MethodsCell-based ERβ and ERα activity assay systems were employed to define a selective ERβ-inhibiting chemical product from a library of natural products. A surgically induced endometriosis mouse model was used to determine whether an ERβ inhibitory drug suppressed endometriosis progression. Mice with endometriosis were randomly separated and then orally treated with vehicle or 25 mg/kg oleuropein (once a day for 21 days), an ERβ inhibitory drug. The volume of endometriotic lesions or luciferase activity of endometriotic lesions was examined to define the growth of ectopic lesions in mice with endometriosis. The metabolite and levels of metabolic enzymes of the liver and kidney were determined in the serum of female mice treated with vehicle and oleuropein (25 mg/kg, once a day for 21 days) to define the toxicity of oleuropein. The in vitro decidualization assay was conducted with normal human endometrial stromal cells and endometriotic stromal cells to determine whether oleuropein overcomes decidualization in endometriosis patients. The pregnancy rate and pup numbers of C57BL/6 J female mice with endometriosis treated with vehicle or oleuropein (n = 10/group) were determined after mating with male mice. The cytokine profile in endometriotic lesions treated with vehicle and oleuropein (25 mg/kg) was determined with a Mouse Cytokine Array Kit.ResultsAmong natural products, oleuropein selectively inhibited ERβ but not ERα activity in vitro. Oleuropein treatment inhibited the nuclear localization of ERβ in human endometrial cells upon estradiol treatment. Oleuropein (25 mg/kg) treatment suppressed the growth of mouse (6.6-fold) and human (sixfold) ectopic lesions in mice with endometriosis compared to the vehicle by inhibiting proliferation and activating apoptosis in endometriotic lesions. Oleuropein treatment did not cause reproductive toxicity in female mice. Additionally, mice with endometriosis subjected to oleuropein treatment had a higher pregnancy rate (100%) than vehicle-treated mice (70%). Furthermore, oleuropein treatment partially recovered the decidualization impact of human endometriotic stromal cells from endometriotic lesions compared to the vehicle. Oleuropein-treated mice with endometriosis exhibited significantly lower levels of cytokines directly regulated by ERβ in ectopic lesions than vehicle-treated mice, illustrating the improvement in the hyperinflammatory state of mice with endometriosis.ConclusionsOleuropein is a promising and novel nutraceutical product for nonhormonal therapy of endometriosis because it selectively inhibits ERβ, but not ERα, to suppress endometriosis progression and improve the fertility of mice with endometriosis.

Hormonal Contraceptive Use and Association with Thromboembolism in Women with Sickle Cell Disease

Introduction Women with sickle cell disease (SCD) require broad access to highly effective contraceptive methods due to high rates of unplanned pregnancy and adverse maternal and fetal outcomes. Combined (estrogen-containing) hormonal contraception carries a known risk of thromboembolism (TE) in the general population, and women with SCD have higher baseline risk of TE, thus use of these agents in women with SCD may further increase that risk. The paucity of safety data on hormonal contraceptive use in women with SCD limits the ability of providers and patients to make informed decisions. Objectives This study aims to use population-level administrative claims data of publicly insured women with SCD in the United States (US) to assess patterns of hormonal contraception use and evaluate risk of TE during the first year of use. We hypothesized that TE rates are higher in women prescribed combined hormonal contraceptives (CHC) as compared to women prescribed progestin-only contraceptives (POC). Methods We obtained data using the Centers for Medicare and Medicaid Services Analytic eXtract (CMS MAX) from 2006-2018. Study population included females of reproductive age (12-44 years) with >3 ICD-9 or ICD-10 codes consistent with SCD. Women had to have ≥12 months of continuous enrollment with at least 6 months of data as 'washout period' prior to enrollment period. A new prescription for hormonal contraception was identified using national drug codes in pharmaceutical claims or ICD-9 or 10 procedure codes. CHC included the combined oral contraceptive pill (OCP), transdermal patch, and vaginal ring. POC included the progestin-only pill, depot medroxyprogesterone acetate (DMPA) injection, intrauterine device (IUD) and subdermal implant. TE was defined as the presence of ≥2 ICD-9 or ICD-10 codes for venous TE (deep vein thrombosis (DVT) or pulmonary embolism (PE)) or arterial TE (stroke or myocardial infarction (MI)). Arterial TE was also required to have an associated inpatient admission. Women were included in the analysis for 12 months after contraception initiation, or censored in the event of either contraceptive switch, pregnancy or abortion, or TE occurrence. Data were summarized descriptively and TE incidence rates were calculated as events per 1,000 person-years. Results We identified a total of 41,012 reproductive-aged women with SCD enrolled in CMS MAX, of whom 22.6% (n=9,261) had received ≥1 new prescription for hormonal contraception. Among women with new contraceptive use, 58.5% (n=5,420) initiated CHC and 41.5% (n=3,841) initiated POC. Median age at the start of contraception was 22.3 years (range: 12.0-43.9) and median age at the start of CHC and POC were 22.1 and 22.7 years respectively. Among CHC users, 84.6% (n=4,584) of women were prescribed the combined OCP, 7.7% (n=419) the transdermal patch, and 7.7% (n=417) the vaginal ring. For POC users, DMPA was prescribed to 72.3% (n=2,777), progestin-only pills to 21.2% (n=816), IUD to 4.2% (n=163) and subdermal implant to 2.2% (n=85) of women. A total of 141 (1.5%) new contraceptive users with SCD were identified to have a TE during the follow-up period. The median time from contraception initiation to TE diagnosis was 183 days (IQR: 82-244). The most common TE event was PE (46.1%) followed by DVT (41.8%), stroke (6.4%), and MI (2.1%); 3.5% of women had multiple TE events. TE rate was 16.4 events per 1,000 person-years in CHC users, and the TE event rate was 17.0 events per 1,000 person-years in POC users (p=0.84). Rates of TE did not differ between the two most commonly used methods in each group, the combined OCP (15.5 events per 1,000 person-years ) and DMPA (17.7 events per 1,000 person-years) (p=0.48). Conclusion Our work provides population-level data regarding contraceptive practices for women with SCD in the US. We found that CHC was more frequently prescribed than POC, and identified low rates of long-acting reversible contraception use. The most frequently prescribed agents were the combined OCP and the DMPA injection. TE rates after initiation of the combined OCP and DMPA did not differ. Although limited by the retrospective study design and use of administrative claims data, this study suggests a similar safety profile for CHC and POC in women with SCD with respect to risk of TE.

The world needs better male contraceptives: What is taking so long?

Forty percent of US pregnancies are unintended despite currently available contraceptives. A substantial number of men use the currently available methods of male contraception, condoms and vasectomy, and a large majority would be interested in novel forms of male contraception if available. Research into male contraception has been ongoing for more than 50 years, with hormonal contraceptives nearing clinical utility and non-hormonal methods hopefully becoming available, albeit with a longer time frame. However, uncertainly regarding benchmarks for the efficacy and safety of male contraception continue to be an issue with development and regulatory approval. In addition, pharmaceutical industry support is minimal with the NIH and Foundations being the main research funders. Given the continuing high rates of unintended pregnancy, many of which are now occurring in areas with extremely restricted access to legal abortion, additional focus and investment in male contraceptive development is imperative.

Structural Interventions to Enable Adolescent Contraceptive Use in LMICs: A Mid-Range Theory to Support Intervention Development and Evaluation.

Enabling contraceptive use is critical for addressing high adolescent pregnancy rates in low- and middle-income countries (LMICs). Broader or 'upstream' determinants, such as poverty, education, and social norms, can affect the knowledge, attitudes, motivation, and ability to access and use contraception. Structural interventions aim to address these broader determinants, e.g., through poverty alleviation from livelihood training or cash transfers, increasing school participation, or changing social norms. We conducted an evidence synthesis using intervention component analysis, a case-based approach, following a systematic mapping of the evidence base. We identified 17 studies with 29 structural intervention arms, which reported adolescent contraceptive use outcomes compared to a control group or baseline. It was not possible to identify with certainty which interventions were 'likely effective' or 'likely ineffective' due to the high heterogeneity of the methods. We built on an existing framework of family planning use to propose three steps to designing interventions: (1) tailor interventions to adolescents' life stages; (2) assess the baseline situation; and (3) select appropriate activities to match the gaps. These steps will aid developers and evaluators of structural adolescent contraceptive interventions to develop an evidence base that is of use across a wide range of settings and use scenarios.

Coenzyme Q10 and Melatonin for the Treatment of Male Infertility: A Narrative Review.

Lifestyle and environmental factors can negatively impact fertility by means of oxidative stress. In this context, antioxidant supplementation therapy has gained much interest in recent years, and different molecules, alone or in combination, have been studied. The purpose of the present review is to investigate the evidence regarding the efficacy of coenzyme Q10 (CoQ10) and melatonin on male infertility. A literature search using PUBMED database from 2000 to October 2022 was performed to explore the role of CoQ10 and melatonin on male reproductive function. The analysis involved a narrative synthesis. CoQ10, alone or in combination, appears to reduce testicular oxidative stress and sperm DNA fragmentation and to improve sperm parameters; particularly sperm motility. Moreover, CoQ10 treatment is associated with higher pregnancy rates, both naturally and through assisted reproductive technology (ART). Larger studies are needed to precisely determine its clinical efficacy. Melatonin is a known antioxidant and preclinical studies have shown its ability to modulate reproductive function through hormonal and immune system regulation and sperm cell proliferation. Regardless, clinical studies are necessary to assess its potential in male infertility.