Effect of weight loss before in vitro fertilization in women with obesity or overweight and infertility: a systematic review and meta-analysis.

The effect of weight loss before in vitro fertilization (IVF) procedures on pregnancy outcomes in women with overweight or obesity and infertility remains controversial. In this systematic review and meta-analysis, we investigated whether weight loss before IVF in these women affected the IVF results and reproductive outcomes. PubMed, Embase, and the Cochrane Library databases were searched from the inception dates until December 2022, using combinations of relevant keywords. Only six randomized controlled trials, including 1627 women with obesity or overweight, were analyzed. The weight change in the intensive care group, compared to the control group who underwent IVF without weight loss was - 4.62 kg (mean difference; 95% confidence interval [CI] - 8.10, - 1.14). Weight loss before IVF did not significantly increase the live birth rate in women with obesity or overweight and infertility (odds ratio, 1.38; 95% CI 0.88, 2.10). The clinical pregnancy, miscarriage, ongoing pregnancy, and ectopic pregnancy rates did not differ between the weight loss and control groups before IVF. This meta-analysis demonstrated that even significant weight loss before IVF in women with obesity or overweight and infertility did not improve the live birth, clinical pregnancy, ongoing pregnancy, or ectopic pregnancy rates. PROSPERO Registration Number: CRD42023455800.

Risk of cardiocerebrovascular diseases is increased in Korean women with polycystic ovary syndrome: a nationwide cohort study.

To investigate the relationship between polycystic ovary syndrome (PCOS) and risk of cardiocerebrovascular disease in Korean women. This longitudinal cohort study using data from the Korean National Health Insurance Service included the women aged 15-44 years diagnosed with PCOS between 2002 and 2019, and the controls were matched 1:3 by age group, income, and region of residence. The endpoint outcomes of this study were the occurrence of ischemic heart disease, cerebrovascular diseases, and combined cardiocerebrovascular diseases in the PCOS and control groups. A stratified Cox proportional hazards regression analysis for matched data was performed to evaluate the relative hazard of events in the PCOS group compared to that in the control group. Among a total of 549,400 participants in the cohort, 137,416 women had a diagnosis of PCOS and 412,118 women did not have it. During a median follow-up of 54 months (interquartile range, 30-78 months), the incidence rates of all cardiovascular, ischemic heart, and cerebrovascular diseases were 6.6, 4.0, and 2.9, respectively, per 1000 person-years for women with PCOS, and 4.8, 2.8, and 2.3, respectively, per 1000 person-years for healthy control women. Women with PCOS had a higher hazard ratio of 1.224 (95% confidence interval, 1.18-1.27) of the composite cardiocerebrovascular diseases than those in the controls after propensity score matching for confounding variables, including body mass index, diabetes mellitus, hypertension, dyslipidemia, physical exercise level, alcohol consumption, current smoking, systolic and diastolic blood pressures, total cholesterol, and triglyceride levels. Hazard ratio for ischemic heart and cerebrovascular diseases was higher in women with PCOS than in the control group (hazard ratio, 1.254; 95% confidence interval, 1.20-1.31 and hazard ratio, 1.201; 95% confidence interval, 1.14-1.27, respectively). PCOS is associated with an increased risk of cardiocerebrovascular diseases in Korean women irrespective of their obesity. Counselling on the management of long-term risk of cardiovascular diseases should be offered to women with PCOS in East Asian countries where PCOS is characterized by a relatively low BMI.

Cumulative pregnancy rate via multiple fresh or frozen embryo transfers in women with current, resected, or recurred endometrioma.

OBJECTIVE: This study aimed to retrospectively analyze the cumulative pregnancy rate (PR) via multiple fresh or frozen embryo transfers (ET) in women with current, resected, or recurred endometrioma. MATERIALS AND METHODS: The IVF data including oocyte pick-up (OPU) and fresh or frozen ET in women with current (37 women; 56 OPU, 18 fresh and 14 frozen ET), resected (24 women; 50 OPU, 17 fresh and 42 frozen ET), or recurred endometrioma (28 women; 49 OPU, 22 fresh and 24 frozen ET) were obtained. All cycles were performed from 2015 to 2022 in a single university hospital. RESULTS: The median serum AMH level (ng/mL) was 1.44, 1.47, and 0.98, respectively. The number of total or mature oocytes, fertilized oocytes, cleavage embryos at day-3, and top-quality embryos at day-3 were all similar in the three groups. Cycles with no oocyte occurred in 2 (3.6%), 1 (2%), and 3 cycles (6.1%), respectively. Freeze-all was performed in 46.3%, 59.2%, and 47.8% of the cycles, respectively (p > 0.05). The cumulative clinical PR per total ET (43.8%, 25.4%, and 21.7%), per OPU (25%, 30%, and 20.4%), and per woman (37.8%, 62.5%, and 35.7%) were all similar in the three groups. The cumulative ongoing pregnancy and live birth rate per total ET, per OPU, and per woman were also similar in the three groups. CONCLUSION: Similarity in ovarian reserve, number of oocytes, number of embryos, cumulative clinical PR, and live birth in the three endometriosis groups indicates that the IVF outcomes in the 'recurrent endometrioma' group are not inferior to 'current' or 'resected' group.

Maternal Polycystic Ovary Syndrome and the Risk of Early Childhood Obesity in Female Offspring: A Nationwide Population-Based Study.

BACKGROUND: To investigate the relationship between polycystic ovary syndrome (PCOS) in Korean women and childhood growth and obesity of their offspring. METHODS: This longitudinal case-control study using the Korean National Health Insurance claims database and the National Health Screening Program for Infants and Children database included women who delivered singletons between January 2007 and December 2008. Offspring's body mass index (BMI) measurements taken between 42 and 80 months of age were compared according to a maternal history of PCOS. RESULTS: Among a total of 131,805 participants, 1,213 women had a history of PCOS and 130,592 women did not. Female offspring aged 66-80 months born to women with PCOS had significantly higher BMI than those born to women without PCOS; there was no significant difference in that of male offspring regardless of maternal PCOS. In the generalized estimating equation and multivariable logistic regression analyses, the female offspring born to women with PCOS had a significantly higher risk of obesity during the age of 42-54 and 66-80 months (odds ratio [OR], 1.6; 95% confidence interval [CI], 1.09-2.21 and OR, 1.5; 95% CI, 1.05-2.15, respectively), than those born to women without PCOS, after adjusting for several confounding factors. CONCLUSION: Maternal PCOS is independently associated with an increased incidence of childhood obesity in female offspring among Korean women. Women with PCOS should consider the risk of early childhood obesity in their daughters, even if they maintain a healthy weight themselves.

Effects of time-restricted feeding on letrozole-induced mouse model of polycystic ovary syndrome.

The present study aimed to investigate whether time-restricted feeding (TRF) ameliorates metabolic and reproductive phenotypes in a letrozole-induced mouse model of polycystic ovary syndrome (PCOS). Sixty female C57BL/6 N mice were randomly divided into two groups according to the type of food received: either a chow or a 60% high-fat diet. Those mice were subcutaneously implanted with letrozole or placebo pellets at four weeks of age. Then, letrozole-treated mice were randomly assigned to different feeding regimens: (1) TRF for 4 h (ZT12-ZT16) or (2) ad libitum diet. After 4 weeks of dietary intervention, estrous cycles were determined with daily vaginal smear examination, and serial tail-tip blood sampling was performed at 5-min intervals for 2 h to measure the luteinizing hormone (LH) pulse frequency, amplitude, and mean LH levels in the diestrus cycle stage. Letrozole-treated mice in the ad libitum group demonstrated multiple PCOS-like phenotypes including ovulatory dysfunction, polycystic ovaries, and increased body weight, parametrial fat weight, adipocyte size and inflammation, and higher expression of Cyp17, Cyp19, and Fshr in the ovary, and Kiss1r and Gnrh in the hypothalamus, elevated serum testosterone levels, and more rapid and elevated LH pulsatility, with increased pulse frequency, amplitude, and mean levels in the diestrus stage, compared with the controls. After TRF for 4 weeks, those phenotypes reverted to normal levels in letrozole-treated mice, except the percentage of diestrus cycles indicating the arrest of estrous cycling which did not differ between the TRF and ad libitum groups. Our results demonstrate that TRF has therapeutic effects on the reproductive and metabolic phenotypes of a letrozole-induced mouse model of PCOS.

Age at Menopause and Suicidal Ideation in Menopausal Women: A Study of Korea National Health and Nutrition Examination Survey Data.

BACKGROUND: Although menopause is considered a risk factor for depression, no association has been established between the risk of suicidal ideation and age at menopause. This study aimed to evaluate the association between age at menopause and suicidal ideation in middle-aged menopausal Korean women. METHODS: This cross-sectional study used data from the Korea National Health and Nutrition Examination Survey (2013-2018). Women aged 40-65 years were divided into the following three categories: primary ovarian insufficiency (POI), early menopause, and menopause, according to age at natural menopause (< 40, 40-45, and > 45 years, respectively). Depressive symptoms were assessed using the Patient Health Questionnaire-9 (PHQ-9). RESULTS: Among 2,232 menopausal women, 25 (1.1%) experienced POI and 114 (5.1%) experienced early menopause. The PHQ-9 items that pertained to low self-esteem and suicidal ideation scored higher in women with POI than in those who experienced menopause after 45 years of age. The prevalence of suicidal ideation differed significantly according to age at menopause (POI, 30.0%; early menopause, 12.7%; menopause, 8.0%; P = 0.016). Logistic regression analysis revealed that POI was significantly associated with suicidal ideation after the adjustment for age, body mass index, and education, household income, and walking levels (odds ratio, 4.2; 95% confidence interval, 1.0-17.7). CONCLUSION: Korean middle-aged women with POI were more likely to have suicidal ideation than those who experienced menopause at 45 years or above, despite not being diagnosed with major depressive disorder.

Risk of Endometrial Polyps, Hyperplasia, Carcinoma, and Uterine Cancer After Tamoxifen Treatment in Premenopausal Women With Breast Cancer.

Importance: The association of tamoxifen use with the risk of uterine diseases, such as endometrial cancer, in premenopausal women with breast cancer remains controversial. However, many studies have reported an increased risk of uterine disease among postmenopausal tamoxifen users. Objective: To investigate the association of tamoxifen use with the risk of endometrial cancer and other uterine diseases in premenopausal women with breast cancer. Design, Setting, and Participants: A nationwide, population-based, retrospective longitudinal cohort study with an 18-year study period was conducted using data obtained from the Korean National Health Insurance Service. Participants included premenopausal women aged 20 to 50 years with breast cancer diagnoses between January 2003 and December 2018. Data were analyzed from April to December 2021. Exposures: Tamoxifen treatment. Main Outcomes and Measures: The incidence of uterine diseases, including endometrial cancer, hyperplasia, polyps, and other uterine cancers, was identified in the study cohort using insurance claim codes. The incidence of uterine diseases per 1000 person-years was compared between women receiving tamoxifen and those not treated with adjuvant hormone therapy. Multivariable Cox proportional hazard regression analysis was performed to determine the risk of each uterine disease. Results: Among 78 320 female participants with a mean (SD) age of 42.1 (6.1) years, 34 637 (44.2%) were categorized into the tamoxifen group and 43 683 (55.8%) were categorized into the control group. Among tamoxifen users, during the mean (SD) follow-up duration of 6.13 (4.15) years, the incidence of newly diagnosed endometrial polyps was 20.13 cases per 1000 person-years, that of endometrial hyperplasia was 13.49 cases per 1000 person-years, that of endometrial cancer was 2.01 cases per 1000 person-years, and that of other uterine cancers was 0.45 cases per 1000 person-years. The risk of endometrial cancer was higher in the tamoxifen group than in the control group (hazard ratio, 3.77; 95% CI, 3.04-4.66) after adjusting for age, body mass index, history of diabetes, hypertension, dyslipidemia, polycystic ovary syndrome, gonadotropin-releasing hormone agonist treatment, and trastuzumab treatment. Conclusions and Relevance: In this longitudinal cohort study, premenopausal Korean women with breast cancer who received tamoxifen as adjuvant hormone therapy had a significantly increased risk of endometrial hyperplasia, polyps, carcinoma, and other uterine cancers compared with those who were not treated with adjuvant hormone therapy. These findings suggest that clinicians should consider the risk of uterine disease among tamoxifen users, including premenopausal women.

Metabolic Disorders in Menopause.

Menopause is an aging process and an important time equivalent to one-third of a woman's lifetime. Menopause significantly increases the risk of cardiometabolic diseases, such as obesity, type 2 diabetes, cardiovascular diseases, non-alcoholic liver disease (NAFLD)/metabolic associated fatty liver disease (MFFLD), and metabolic syndrome (MetS). Women experience a variety of symptoms in the perimenopausal period, and these symptoms are distressing for most women. Many factors worsen a woman's menopausal experience, and controlling these factors may be a strategy to improve postmenopausal women's health. This review aimed to confirm the association between menopause and metabolic diseases (especially MetS), including pathophysiology, definition, prevalence, diagnosis, management, and prevention.

Correlation of oocyte number with serum anti-Müllerian hormone levels measured by either Access or Elecsys in fresh in vitro fertilization cycles.

OBJECTIVE: The aim of this study was to assess the correlation of oocyte number with serum anti-Müllerian hormone (AMH) levels measured by two automated methods (Access or Elecsys) in fresh stimulated in vitro fertilization (IVF) cycles. METHODS: In this retrospective study at a university hospital, data were collected from 243 fresh stimulated IVF cycles performed from August 2016 to December 2020. The serum AMH level was measured by Access in 120 cycles and by Elecsys in 123 cycles. The cut-off of serum AMH for prediction of poor responders (three or fewer oocytes) or high responders (15 or more oocytes) was calculated by the receiver operating characteristic curve analysis. RESULTS: For the two automated methods, the following equations were derived: total oocyte number=2.378+1.418×(Access-AMH) (r=0.645, p<0.001) and total oocyte number=2.417+2.163×(Elecsys-AMH) (r=0.686, p<0.001). The following combined equation could be derived: (Access-AMH)=0.028+1.525×(Elecsys-AMH). To predict poor responders, the cut-off of Access-AMH was 1.215 ng/mL (area under the curve [AUC], 0.807; 95% confidence interval [CI], 0.730-0.884; p<0.001), and the cut-off of Elecsys-AMH was 1.095 ng/mL (AUC, 0.848; 95% CI, 0.773-0.923; p<0.001). To predict high responders, the cut-off of Access-AMH was 3.450 ng/mL (AUC, 0.922; 95% CI, 0.862-0.981; p<0.001), and the cut-off of Elecsys-AMH was 2.500 ng/mL (AUC, 0.884; 95% CI, 0.778-0.991; p<0.001). CONCLUSION: Both automated methods for serum AMH measurement showed a good correlation with oocyte number and good performance for predicting poor and high responders in fresh stimulated IVF cycles. The Access method usually yielded higher measured serum AMH levels than the Elecsys method.

Up-to-Date Knowledge on Osteoporosis Treatment Selection in Postmenopausal Women.

The concept of a super-aged society has led to a steady increase in the average lifespan and hence, interest in a healthy life has increased. Aging is a major risk factor for many diseases, including osteoporosis. Osteoporotic fractures have a significant impact on the quality of life of the elderly and hence, it is pivotal to provide effective treatment of osteoporosis after menopause. Osteoporosis requires proper management and the treatment must be centered on long-term goals. New drugs with diverse mechanisms have been developed for treating osteoporosis. Current management of osteoporosis generally focuses on the importance of risk-based strategies to maximize the effectiveness of existing treatments and mitigate potential negative side-effects. Additionally, there is a need for sequential treatment of osteoporosis in the future. This review discusses the dynamic strategies for osteoporosis treatment and the importance of long-term management in postmenopausal women.

Management of endometrial polyps in infertile women: A mini-review.

Considerable disagreement exists regarding whether endometrial polyps should be removed before attempting natural pregnancy and before pregnancy via intrauterine insemination (IUI) or in vitro fertilization (IVF). Through a literature review, we obtained information on the impact of endometrial polyps and polypectomy on fertility outcomes. Several observational studies have suggested that women with unexplained infertility may benefit from endometrial polypectomy for a future natural pregnancy. A few studies reported benefits from endometrial polypectomy in infertile women who plan to undergo IUI. However, no strong evidence supports polypectomy as a way to improve the pregnancy rate in infertile women who plan to undergo IVF or polypectomy during controlled ovarian stimulation for IVF. Although no studies have defined criteria for the polyp size that should be removed in infertile women, clinicians should be aware that small endometrial polyps (<10 mm) sometimes regress spontaneously. Endometrial polypectomy is currently justified in patients with repeated IVF failure, but more studies are needed to verify that endometrial polypectomy itself will eventually increase the pregnancy rate. Although several mechanisms by which endometrial polyps exert a negative effect on fertility have emerged, there is no consensus about the proper management of endometrial polyps in infertile women. Therefore, the management of endometrial polyps should be individualized depending on the patient's situation and clinician's preference.

Injection funnel persistence time and oolemma resistance during intracytoplasmic sperm injection and subsequent embryo development.

OBJECTIVE: This study aimed to investigate whether the injection funnel persistence time and oolemma resistance during the intracytoplasmic sperm injection (ICSI) are associated with subsequent embryo quality. DESIGN: A prospective observational study at a university hospital. METHODS: One hundred and twenty normal-appearing metaphase II oocytes were collected from 54 ICSI cycles. Injection funnel was observed at 0, 30, 60, and 90 s after ICSI, and the injection funnel persistence time was assigned to "no funnel," "0-30," "30-60," "60-90," and ">90 s." The degree of oolemma resistance during ICSI was recorded as "no," "mild," "moderate," and "severe." Subsequent embryos on day 3 after ICSI were evaluated morphologically, and formation of top-quality embryo and embryo score was assessed. We newly developed "oolemma score," based on the injection funnel persistence time and oolemma resistance, and the predictability of top-quality embryo was assessed. RESULTS: Among the five groups by injection funnel persistence time, the proportion of top-quality embryo and embryo score (64.3%, 32) was highest in the "30-60 s," but not significant. Among the four groups by oolemma resistance, the proportion of top-quality embryo and embryo score (53.7%, 32) was highest in "no group." The proportion of top-quality embryo in "no group" was significantly higher than "moderate group" (p = 0.012) and "severe group" (p = 0.043). The median embryo score in "no group" was significantly higher than "severe group" (p = 0.041). Newly developed "oolemma score" could predict well the formation of top-quality embryo with a statistical significance (cutoff >14.5, area under the curve 0.695, p < 0.001). CONCLUSION: Embryo quality or score is more closely associated with oolemma resistance during ICSI. New "oolemma score" would help to identify embryo developmental potential of each mature oocyte in ICSI cycles.

The Largest Uterine Leiomyoma Removed by Robotic-Assisted Laparoscopy in the Late Reproductive Age: A Case Report.

Uterine leiomyoma is a very common gynecological tumor in the reproductive years. Recent studies have shown that surgical treatment of uterine leiomyoma using robotic-assisted laparoscopic myomectomy (RALM) is associated with significantly fewer complications, lower estimated blood loss, fewer conversions, and less bleeding than conventional laparoscopic myomectomy. This study reports the case of a giant uterine leiomyoma treated using RALM. A 50-year-old woman was referred to our outpatient clinic with progressive abdominal distension. Ultrasonography and magnetic resonance imaging were performed and showed a markedly enlarged uterus containing a 28-cm uterine myoma. RALM confirmed the 28-cm subserosal myoma on the posterior wall of the uterus. The myoma was enucleated, and the myometrial and serosal defect was repaired with a continuous suture using barbed suture materials. The entire myoma was removed using an electric morcellator. The operation lasted for 190 minutes. The total weight of the removed myoma was 3,262 g, and uterine leiomyoma was pathologically diagnosed. There were no postoperative complications. Although the treatment of huge myomas using RALM is controversial and technically demanding, we successfully performed RALM in a patient with a large myoma. This case confirms the efficiency, reliability, and safety of a robotic-assisted laparoscopic approach for removing a huge myoma. In a well-selected case, RALM can be performed by experienced surgeons regardless of the size of fibroids.

Efficacy and side effect of ritodrine and magnesium sulfate in threatened preterm labor.

OBJECTIVE: In terms of efficacy, several previous studies have shown that the success rate in inhibiting preterm labor was not different between magnesium sulfate and ritodrine. However, there is a paucity of information regarding the efficacy of both medications after consideration of intra-amniotic infection, which is one of the most important prognostic factors in patients of threatened preterm birth. The objective of this study was to compare the efficacy and safety of magnesium sulfate with that of ritodrine in preterm labor. METHODS: In this retrospective cohort study, we included patients who were admitted and treated with either ritodrine or magnesium sulfate with the diagnosis of preterm labor at 24-33.6 weeks of gestational age between January 2005 to April 2015. Patients were divided into 2 groups according to the first-used tocolytics (ritodrine group and magnesium sulfate group). We compared the efficacy and prevalence of side effect in each group. The efficacy of both tocolytics was evaluated in terms of preterm delivery within 48 hours, 7 days, or 37 weeks of gestation and need for 2nd line therapy. RESULTS: A total number of 201 patients were enrolled including 177 cases in ritodrine group and 24 cases in magnesium sulfate group. The efficacy of both tocolytics (preterm delivery within 48 hours, 7 days, or 37 weeks of gestation and need for 2nd line therapy) was not different between the 2 groups of cases. In multivariate analysis, gestational age at treatment, twin gestation, intra-amniotic infection and maternal C-reactive protein (CRP) was associated with treatment failure (preterm delivery within 48 hours), but the type of tocolytics was not significantly associated with treatment failure. The type of side effect was different in the 2 groups, but the frequency of total adverse effect, need for discontinuation of therapy because of maternal adverse effect, and severe adverse effect were not different between the two groups of cases. CONCLUSION: The efficacy and safety of magnesium sulfate was similar to ritodrine, and can be a substitute tocolytics. Additionally, failure of tocolytic therapy was determined by gestational age at treatment, twin gestation, intra-amniotic infection, and maternal CRP, not by the type of tocolytics.