Comparison of resumption of ovulation after cessation of oral contraceptives and medroxyprogesterone acetate in women with polycystic ovary syndrome.

OBJECTIVE: Both oral contraceptive pills (OCPs) and cyclic medroxyprogesterone acetate (MPA) are widely used to control menstrual abnormalities in women with polycystic ovary syndrome (PCOS). We aimed to evaluate the chance of ovulation resumption after cessation of OCPs and MPA in women with PCOS. METHODS: A retrospective study was conducted of women with PCOS who were treated with OCPs or cyclic MPA from September 2015 to March 2019. After cessation of medication, ovulation was assessed using basal body temperature and/or measurement of serum progesterone. The odds ratio for ovulation resumption was assessed with multivariable logistic regression. Additionally, doubly robust analysis was performed with inverse-probability-weighted analysis and regression adjustment based on the covariate balancing propensity score to adjust for the effect of covariates on the treatment assignment. RESULTS: Among 272 women with PCOS, 136 were prescribed OCPs and 136 were prescribed cyclic MPA. Ovulation resumed in 18.4% of women (n = 25) after cessation of MPA and in 24.3% of women (n = 33) after cessation of OCPs. The odds of ovulation resumption in MPA users were comparable with those in OCP users (adjusted odds ratio (aOR) 1.00, 95% confidence interval (CI) 0.89-1.12). After multiple imputation due to missing values, the results did not change substantially (aOR 0.99, 95% CI 0.89-1.10). CONCLUSIONS: Among women with PCOS, MPA users have a similar chance of ovulation resumption as OCP users after cessation of medication. Cyclic MPA can be a good alternative to OCPs in women for whom OCPs are contraindicated or who decline to take OCPs.

A Successful Live Birth From a Vitrified Oocyte for Fertility Preservation of a Patient With Borderline Ovarian Tumor Undergoing Bilateral Ovarian Surgery: A Case Report.

This article reports the live birth of a healthy newborn using vitrified-warmed oocytes from fertility preservation before ovarian surgery. The patient in our case underwent two cycles of controlled ovarian stimulation before laparoscopic bilateral ovarian cystectomy for endometriosis, and a total of 23 mature oocytes were vitrified. After surgery, her pathologic reports revealed a serous borderline tumor and endometrioma. Fifteen months after her second surgery of laparoscopic right salpingo-oophorectomy and left ovarian cystectomy owing to recurrence, she had been married by then, and three of the frozen oocytes were thawed for intracytoplasmic sperm injection. These oocytes were cryopreserved for 2.5 years. All three were fertilized, and two grade-A cleavage-stage embryos were transferred. A singleton pregnancy was achieved, resulting in the delivery of a healthy baby boy at 39.3 weeks of gestation. Oocyte cryopreservation is an effective method for fertility preservation prior to ovarian surgery when ovarian function decline is predictable.

Impact of BRCA mutations and hormone receptor status on reproductive potential in breast cancer patients undergoing fertility preservation.

OBJECTIVE: To identify whether the BRCA mutations and hormone receptor status affect the ovarian reserve and ovarian stimulation outcomes in breast cancer patients undergoing fertility preservation. METHODS: A total of 117 women diagnosed with breast cancer who were referred to the fertility preservation clinics at Seoul National University Bundang Hospital and Seoul National University Hospital between September 2012 and July 2019 undergone ovarian stimulation for oocyte retrieval. Basal characteristics including age, BMI, basal AMH, basal FSH, and fertility preservation outcomes such as the number of retrieved oocytes and mature oocytes were compared retrospectively. RESULTS: BRCA1 mutation was noted in 25 women, and BRCA2 mutation was observed in 35 women. Positive estrogen receptor status was noted in 87 women, and positive progesterone receptor status was noted in 69 women. HER2 was positive in 55 women, and 19 women were diagnosed with triple-negative breast cancers. The number of total oocytes retrieved was lower in patients with BRCA mutation (8.3 ± 5.4 vs. 15.3 ± 8.7, p = .002). The number of mature oocytes retrieved was also lower in BRCA carriers (4.7 ± 4.2 vs. 8.7 ± 7.9, p = .025). Triple-negative breast cancer (TNBC) patients were younger than non-TNBC patients (30.3 ± 4.8 vs. 33.9 ± 5.0, p = .007). The rate of mature oocyte rate was higher in TNBC patients (68.6%±20.6 vs. 52.5%±29.7, p = .037). CONCLUSIONS: Our study demonstrated that BRCA carriers with breast cancer had comparable ovarian reserve to non-carriers but the response to ovarian stimulation was lower. We also observed that oocyte maturity was higher in TNBC patients, however age might be a confounding factor of this result.

Prediction model of persistent ovulatory dysfunction in Korean women with polycystic ovary syndrome.

AIM: There is no validated tool to predict persistent ovulatory dysfunction after medication with oral contraceptives in women with polycystic ovary syndrome (PCOS), which is the most severe subtype of PCOS. We aimed to build a model to predict persistent ovulatory dysfunction after medication of oral contraceptives in women with PCOS. METHODS: A total of 286 patients with PCOS were treated with and without oral contraceptives at a tertiary academic medical center. Data were obtained from the electronic medical record system between January 2016 and March 2019. A risk prediction model was developed using multivariable logistic regression. Model 1 was based on age and chief complaints and Model 2 further included predictors evaluated during a clinic visit. Model 3 additionally included laboratory findings. RESULTS: Of the study population, ovulatory dysfunction was persistent in 117 patients (40.9%). Compared with the simple model (Models 1 and 2), the full prediction model (Model 3) had better Akaike's information criterion (286, 244 vs. 225) and the area under the curve (AUC) increased from 0.74 and 0.79 to 0.84. The full model included 7 covariates measured during the evaluation of PCOS, and two covariates were significant predictors of persistent ovulatory dysfunction in PCOS: age (OR 0.91; 95% CI 0.84-0.97), and anti-Müllerian hormone (OR 1.17; 95% CI 1.09-1.26). This model demonstrated good discrimination (AUC, 0.84) and calibration (Hosmer-Lemeshow goodness of fit test, p = 0.74). CONCLUSIONS: This prediction model was shown to be a useful method for predicting persistent ovulatory dysfunction after oral contraceptive medication in patients with PCOS.

Clinical efficacy of dual trigger with human chorionic gonadotropin and a gonadotropin-releasing hormone agonist for women undergoing fertility preservation.

Purpose: To determine the optimal maturation method to increase the yield of mature oocytes, especially for cancer patients with fewer chances of fertility preservation (FP) before gonadotoxic therapy. Methods: A total of 373 cycles in 293 patients undergoing controlled ovarian stimulation (COS) for FP using a gonadotropin-releasing hormone (GnRH) antagonist protocol were enrolled. The control group (n = 225) received 250 µg of recombinant human chorionic gonadotropin (rhCG) while the study group (n = 148) received 250 µg of rhCG and 0.2 mg of triptorelin for triggering. Subgroup analyses were performed for stimulation cycles with diminished ovarian reserve (DOR; anti-Müllerian hormone (AMH) levels <1.1 ng/ml, n = 86), with endometrioma (n = 104), or with breast cancer and endometrial cancer using 5 mg of letrozole during the COS cycles (n = 84). Results: There was no significant difference in the baseline characteristics or the number of total and mature oocytes between the two groups. Subgroup analyses for women with endometrioma or DOR showed similar results. However, the dual trigger group had a significantly higher number of mature oocytes than the rhCG trigger group in breast and endometrial cancer patients using letrozole during the COS cycles (6.9 ± 6.0 vs. 4.6 ± 3.6, p = 0.034). The maturation rate was higher in the dual trigger group, although the difference was not statistically significant (59.3 ± 26.7 vs. 50.0 ± 28.0, p = 0.124). Conclusions: Dual triggering can be an efficient maturation method to maximize the yield of mature oocytes in breast or endometrial cancer patients using letrozole-combined GnRH antagonist protocol for FP.

Operative and Obstetric Outcomes after Single-port Laparoscopic Myomectomy: A Retrospective Single-center Analysis of 504 Cases.

STUDY OBJECTIVE: To analyze the obstetric and operative outcomes of 504 cases of single-port laparoscopic myomectomy (SPLM). DESIGN: Single-center retrospective study. SETTING: A tertiary university hospital. PATIENTS: A total of 502 patients (504 SPLM procedures) who underwent SPLM for symptom relief or growing myomas between October 2009 and April 2020. INTERVENTIONS: Data on patient demographics, operative variables (estimated blood loss, hemoglobin decrease, operation time, perioperative complications, and postoperative hospital stay), and obstetric outcomes (the surgery-to-pregnancy interval and birth-related outcomes) were obtained from medical records and analyzed. MEASUREMENTS AND MAIN RESULTS: The mean age of the patients was 40.6 ± 6.6 years. The patients had had an average of 2.3 ± 2.2 myomas removed; the largest myoma size was 6.8 ± 2.4 cm. The mean operation time, postoperative hemoglobin decrease, and postoperative hospital stay duration were 112.9 ± 45.3 minutes, 1.7 ± 1.1 g/dL, and 2.2 ± 1.4 days, respectively. The overall rate of postoperative complications was 7.7% (39/504), and the common complications were transfusions (16/504, 3.1%) or wound problems (15/504, 3.0%). Conversion to multiport or open myomectomy was required in 0.8% of the cases (4/504). A total of 376 women were of child-bearing age, and 56 attempted to become pregnant after surgery. The mean interval from surgery to pregnancy was 15.6 ± 12.2 months. The obstetric outcomes were pregnancy (42/56, 75.0%), live birth (39/56, 69.6%), and miscarriage (2/56, 3.6%). One pregnant woman was lost to follow-up. The 39 live births predominantly involved full-term delivery (36/39, 92.3%), mostly through cesarean section (36/39, 92.3%). No postpartum complications were reported. The 2 most common obstetric complications were preterm labor (7.6%) and gestational diabetes (5.1%). CONCLUSION: SPLM seems to be an effective procedure with good operative and postoperative obstetric outcomes for women with myomas who require surgery and may wish to subsequently become pregnant.

Use of haemostatic gel in the management of cervical pregnancy: a case report.

PURPOSE: This case report aimed to describe haemostatic agents with systemic methotrexate (MTX) as an effective management for cervical pregnancy with bleeding. CASE PRESENTATION: A 34-year-old nulligravida patient was referred due to vaginal spotting and lower abdominal discomfort, and was diagnosed with a cervical pregnancy at 6 weeks of gestation. The patient was treated with a multi-dose MTX regimen, and the bleeding was successfully controlled with haemostatic agents, which were applied at the bleeding site of the cervix. After completion of MTX treatment, beta human chorionic gonadotropin (ß-hCG) decreased to undetectable range. Furthermore, patients could preserve her uterus and maintain fertility. CONCLUSION: Haemostatic agents can be regarded as an effective option for vaginal bleeding due to cervical pregnancy.

Effects of cyclic adenosine monophosphate modulators on maturation and quality of vitrified-warmed germinal vesicle stage mouse oocytes.

BACKGROUND: It is still one of the unresolved issues if germinal vesicle stage (GV) oocytes can be successfully cryopreserved for fertility preservation and matured in vitro without damage after warming. Several studies have reported that the addition of cyclic adenosine monophosphate (cAMP) modulators to in vitro maturation (IVM) media improved the developmental potency of mature oocytes though vitrification itself provokes cAMP depletion. We evaluated whether the addition of cAMP modulators after GV oocytes retrieval before vitrification enhances maturation and developmental capability after warming of GV oocytes. METHODS: Retrieved GV oocytes of mice were divided into cumulus-oocyte complexes (COCs) and denuded oocytes (DOs). Then, GV oocytes were cultured with or without dibutyryl-cAMP (dbcAMP, cAMP analog) and 3-isobutyl-l-methylxanthine (phosphodiesterase inhibitor) during the pre-vitrification period for 30 min. RESULTS: One hour after warming, the ratio of oocytes that stayed in the intact GV stage was significantly higher in groups treated with cAMP modulators. After 18 h of IVM, the percentage of maturation was significantly higher in the COC group treated with dbcAMP. The expression of F-actin, which is involved in meiotic spindle migration and chromosomal translocation, is likewise increased in this group. However, there was no difference in chromosome and spindle organization integrity or developmental competence between the MII oocytes of all groups. CONCLUSIONS: Increasing the intracellular cAMP level before vitrification of the GV oocytes maintained the cell cycle arrest, and this process may facilitate oocyte maturation after IVM by preventing cryodamage and synchronizing maturation between nuclear and cytoplasmic components. The role of cumulus cells seems to be essential for this mechanism.

Oocyte cryopreservation for fertility preservation in women with ovarian endometriosis.

RESEARCH-QUESTION: What is the clinical usefulness of oocyte cryopreservation for fertility preservation in women with ovarian endometriosis? DESIGN: Clinical characteristics were retrospectively analysed in 34 women with endometrioma before a planned ovarian cystectomy. Ovarian stimulation outcomes were compared according to laterality. A one-to-one propensity score-matched analysis was conducted to compare ovarian stimulation outcomes of the first cycle in patients with endometrioma undergoing fertility preservation with those in infertile patients without endometrioma who underwent IVF treatment. The number of oocytes cryopreserved in repeated ovarian stimulation cycles was analysed. RESULTS: The mean endometrioma size at diagnosis was 6.0 ± 2.5 cm. The mean age, serum anti-Mullerian hormone levels and number of oocytes cryopreserved were 30.7 ± 5.9 years, 1.85 ± 1.14 ng/ml, and 4.8 ± 3.2, respectively. The number of oocytes cryopreserved in bilateral endometrioma compared with unilateral endometrioma patients was 4.1 ± 2.9 versus 5.7 ± 3.4 (P = 0.600). In the propensity score-matched cohort (n = 22 per group), the number of oocytes retrieved was significantly lower in the patients with endometrioma undergoing fertility preservation compared with that in infertile patients without endometrioma (5.4 ± 3.8 versus 8.1 ± 4.8; P = 0.045). A total of 13 (38.2%) patients with endometrioma underwent repeated stimulation. The median (interquartile range) number of cryopreserved oocytes at the first and the second cycle were 3.0 (2.5-6.0) and 5.0 (2.5-7.5), respectively. CONCLUSIONS: Women with endometrioma should be counselled about oocyte cryopreservation for fertility preservation before surgery. The number of cryopreserved oocytes can be increased by repeated oocyte retrieval.

The effects of letrozole on women with endometriosis undergoing ovarian stimulation for in vitro fertilization.

This study aimed to analyze the effects of a new protocol with letrozole on the outcomes of in vitro fertilization (IVF) cycles in women with endometriosis. This retrospective cohort study was conducted for women diagnosed with endometriosis undergoing IVF from an infertility clinic. A new protocol, combination therapy with letrozole and gonadotropin, was used from August 2016 to January 2018 ('protocol 1', n = 38). From March 2014 to July 2016, conventional IVF with gonadotropin was administered ('protocol 2', n = 26). Age and ovarian reserve were comparable between the two groups. The patients who received protocol 1 resulted in a significantly lower peak estradiol level in IVF compared with those received protocol 2 (722 ± 1076 pg/mL versus 2168 ± 1521 pg/mL, p < .001). The length of stimulation, the total dose of gonadotropin, number of oocytes retrieved, fertilization rates, and number of embryos obtained were similar between the two groups. The mean percentage of mature oocytes was lower (69.9 ± 23.7% versus 80.2 ± 21.0%, p = .029) in patients with protocol 1. While maintaining low estrogen levels, the combination therapy with letrozole and gonadotropin produce similar oocyte and embryo yield to the conventional IVF protocol in women with endometriosis.

Erratum: Correction of Author ORCID in the Article: Efficacy of Random-start Controlled Ovarian Stimulation in Cancer Patients.

This corrects the article on p. 290 in vol. 30, PMID: 25729252.

Effects of Natural Progesterone and Synthetic Progestin on Germ Layer Gene Expression in a Human Embryoid Body Model.

Natural progesterone and synthetic progestin are widely used for the treatment of threatened abortion or in in vitro fertilization (IVF) cycles. This in vitro study aimed to assess whether the treatment with natural progesterone or synthetic progestin influences the germ layer gene expression on the early human embryonic development using human embryonic stem cells (hESCs)-derived embryoid bodies (hEBs) as a surrogate of early stage human embryonic development. Human EBs derived from hESCs were cultured for nine days, and were treated with natural progesterone (P4) or synthetic progestin, medroxyprogesterone acetate (MPA) at 10-7 M for five days. To reverse the effects of treatment, mifepristone (RU486) as progesterone antagonist was added to the hEBs for four days starting one day after the initiation of treatment. Mouse blastocysts (mBLs) were cultured in vitro for 24 h, and P4 or MPA at 10-7 M was treated for an additional 24 h. The treated embryos were further transferred onto in vitro cultured endometrial cells to evaluate chorionic gonadotropin (CG) expression. To analyze the effects of P4 or MPA, the expression of differentiation genes representing the three germ layers was investigated, GATA-binding factor 4 (GATA4), α-fetoprotein (AFP), hepatocyte nuclear factor (HNF)-3ß, hepatocyte nuclear factor (HNF)-4α (endoderm), Brachyury, cardiac actin (cACT) (mesoderm), and Nestin (ectoderm), using quantitative reverse transcription PCR (qRT-PCR) and immunostaining. Significantly lower expressions of HNF-3ß, HNF-4α, Brachyury, and Nestin were observed in MPA-treated hEBs (all p < 0.05), which was negated by RU486 treatment. This inhibitory effect of MPA was also observed in mouse embryos. Conclusively, the effects of natural progesterone and synthetic progestin may differ in the germ layer gene expression in the hEB model, which suggests that caution is necessary in the use of progestogen.

A successful live birth with in vitro fertilization and thawed embryo transfer after conservative treatment of recurrent endometrial cancer.

Estrogen-dependent early stage endometrial cancer is relatively common in young women of reproductive age. The standard treatment is hysterectomy and bilateral salpingo-oophorectomy (BSO), even in early stage well-differentiated endometrial cancer patients. This surgical option results in permanent loss of fertility. There have been some reports of live births using in vitro fertilization after conservative management of endometrial cancer with high-dose progestin for the purpose of fertility preservation. However, most were not recurrent cases and pregnancy was achieved through conventional in vitro fertilization, which usually raises serum estradiol levels and may lead to the recurrence of endometrial cancer. To date, it is hard to find a case that can be referred for any possible different approach needed for the patients who experience recurrence. Here we report a successful live birth with in vitro fertilization using letrozole to maintain physiological levels of estradiol, and subsequent thawed embryo transfer after elective cryopreservation of embryos in a patient with recurrent endometrial cancer. There has been no evidence of disease recurrence at one year after delivery.

Relationship between serum anti-Mullerian hormone with vitamin D and metabolic syndrome risk factors in late reproductive-age women.

The relationship between serum anti-Mullerian hormone (AMH) with vitamin D (25OH-D) and metabolic syndrome (MetS) risk was evaluated in healthy, late reproductive-age (35-49 years) women with regular menstrual cycles. Among the 291 participants (mean age = 42.5 years), most (76.6%, n = 223) were serum vitamin D insufficient (<20 ng/ml). Mean serum levels of AMH and vitamin D were 2.04 ng/mL and 15.9 ng/mL, respectively. There was no correlation between AMH and 25OH-D after adjustment for age (r = -0.093, p = 0.113). Subjects with higher MetS score, higher waist circumference, and higher diastolic blood pressure had significantly higher serum AMH levels when adjusted for age, but the association attenuated when BMI was included. There was no significant correlation between MetS risk components with serum level of AMH or vitamin D. In conclusion, there was no association between AMH with serum 25OH-D or MetS risk factors in this population.

Advantages of Single-Port Laparoscopic Myomectomy Compared with Conventional Laparoscopic Myomectomy: A Randomized Controlled Study.

STUDY OBJECTIVE: To compare operative outcomes of single-port laparoscopic myomectomy (SP-LM) vs conventional laparoscopic myomectomy (CLM), including subjective and objective cosmetic aspects. DESIGN: Prospective randomized controlled trial (Canadian Task Force classification I). SETTING: University hospital. PATIENTS: Women with uterine myoma scheduled for laparoscopic myomectomy. INTERVENTIONS: Sixty-six women were assigned at random to either the SP-LM or CLM group. Surgical outcomes, including patient and observer scar assessments, were evaluated between the groups according to the intention-to-treat principle. MEASUREMENTS AND MAIN RESULTS: There were no significant differences in demographic characteristics and properties of myomectomy between the groups. There also were no differences in surgical outcomes, such as operation time, estimated blood loss, and complications, between the 2 groups. The mean total score of the Observer Scar Assessment Scale was lower in the SP-LM group at 1 week (13.0 ± 3.2 vs 18.3 ± 4.8; p < .001) and 8 weeks (9.9 ± 3.2 vs 14.3 ± 3.8; p < .001) after discharge. Similar results were obtained for the Patient Scar Assessment Scale at 1 week (11.6 ± 7.2 vs 18.5 ± 12.8; p = .024) and 8 weeks (9.5 ± 6.0 vs 18.8 ± 9.1; p < .001) after discharge. Postoperative pain and analgesic consumption did not differ between the groups, except in patient-controlled analgesia consumption at 6 hours after operation, which was lower in the SP-LM group (12.7 ± 6.3 mL vs 16.4 ± 6.2 mL; p = .039). Operative outcomes were similar in the 2 groups. CONCLUSION: SP-LM is associated with more favorable cosmetic outcomes and better patient satisfaction compared with CLM. There were no differences in operative outcomes and complications between the 2 modalities.

Incidence Rate of Atypical Femoral Fracture after Bisphosphonates Treatment in Korea.

BACKGROUND: Atypical femoral fracture (AFF) has been high-lightened, because it was associated with the long-term use of bisphosphonate. Comparing western countries, the incidence rate of AFF was unclear in East Asian patients. Our purposes were to estimate the incidence rate of radiologically defined AFF in Korea, and to determine the association between occurrence of AFF and long-term use of bisphosphonate. METHODS: We conducted a hospital-based, retrospective cohort study in patients aged ≥ 45 years, who took bisphosphonate. The occurrence of AFF was estimated by using incidence rate, and the age-adjusted incidence rate to U.S. 2010 Census data. The association between occurrence of AFF and the duration of bisphosphonate use was examined. The cumulative probability of AFF was plotted per each duration of bisphosphonate use. RESULTS: Among 10,338 individuals who took bisphosphonate, 13 patients with AFF following use of bisphosphonate were identified. The incidence rate was 85.9/100,000 person-years (95% confidence interval [CI], 50.2-146.9), and age-adjusted incidence rate was 72.7/100,000 person-years (95% CI, 29.1-175.8). In Poisson regression analysis, higher body mass index (BMI) was associated with an increased risk of AFF (relative risk, 1.2; 95% CI, 1.004-1.359). The cumulative probability of AFF increased abruptly when the duration of bisphosphonate use was 4 years or more. CONCLUSION: Among Korean patients, the incidence rate of AFF was on a par with those of western countries, and this can provide basic information to conduct further studies by evaluating risk and benefit of continuing bisphosphonate.

Successful in Vitro Fertilization and Embryo Transfer after Transplantation of Cryopreserved Ovarian Tissue: Report of the First Korean Case.

For patients at risk of premature ovarian failure with cancer treatment, it is an important option to re-implant the ovarian tissue (OT) after cryopreservation to preserve endocrine function and fertility. With this technique, about 30% of pregnancy success rate and about 90 live births have been reported to date. However, there has been no case report of successful in vitro fertilization (IVF) and embryo transfer (ET) with oocytes collected from transplanted cryopreserved OT in Korea. We report a 30-year old woman with rectal cancer who underwent IVF and ET after cryopreserved OT thawing and re-implantation. She has been diagnosed with stage IIIC rectal cancer after surgery, and right ovary was removed and cryopreserved between cycles of chemotherapy. After completion of chemotherapy and radiotherapy, the patient underwent orthotopic transplantation of cryopreserved OTs. Three months after transplantation, the serum follicle-stimulating hormone level decreased from 91.11 mIU/mL to 43.69 mIU/mL. Thereafter, the patient underwent 11 ovarian stimulation cycles, and in 7 cycles, follicle growth was observed at the OT graft site. In one of these cycles, the oocyte was successfully retrieved and one embryo was transplanted after IVF. The patient was not pregnant, but the cryopreservation of OT can save the fertility after anticancer chemotherapy.

Variation in MicroRNA Expression Profile of Uterine Leiomyoma with Endometrial Cavity Distortion and Endometrial Cavity Non-Distortion.

The expression profile of microRNA (miRNA) in uterine leiomyoma (UL) cells is different from that in normal uterine myometrial (UM) cells. The effect of UL cells on uterine receptivity might vary according to their ability to distort the uterine endometrial cavity. However, the variation in miRNA expression profiles between endometrial cavity-distorting leiomyoma (ECDL) and endometrial cavity non-distorting leiomyoma (ECNDL) cells remains unknown. This study aimed to elucidate whether the expression profile of miRNAs in ECDL cells is dissimilar to that of ECNDL cells in uterus. Pelviscopic myomectomy was performed to obtain tissue samples of UL and their corresponding normal UM tissues (matched) from patients with UL (n = 26), among whom women with ECNDL and ECDL numbered 15 and 11, respectively. The relative expression of hsa-miR-15b, -29a, -29b, -29c, -197, and -200c as well as the candidate target genes in UL cells was compared to those in the matched UM cells using qRT-PCR to assess their ability to cause ECD. The spatial expression of miRNAs and target genes in the UL tissues was analyzed using in situ hybridization. Target gene expression was analyzed using qPCR after transfection with the mimics and inhibitors of miRNAs in UL cells. The relative expression level of miR-15b was upregulated, and the relative expression levels of miR-29a, -29b, -29c, -197, and -200c were downregulated in UL cells compared to those in UM cells. The relative expression levels of progesterone receptor, estrogen receptor, and matrix metalloproteinases (MMPs) were upregulated in UL cells compared to those in UM cells. The relative expression levels of miR-29c and -200c were downregulated, and the relative expression levels of estrogen receptor, MMPs and tissue inhibitors of metalloproteinases (TIMPs) were upregulated in ECDL cells compared to those in ECNDL cells. The expression profile of miRNAs in UL cells varied with respect to the occurrence or absence of endometrial cavity distortion. The biochemical properties of UL might be regulated by miRNAs in order to alter their effect on structural homeostasis of the uterus.

Proteomic analysis of human follicular fluid in poor ovarian responders during in vitro fertilization.

Poor ovarian response (POR) in controlled ovarian stimulation is often observed during in vitro fertilization and embryo transfer cycles and it is a major problem. A POR has been found to be related to several factors, including advanced age, high body mass index, and history of ovarian or pelvic surgery. However, it is difficult to predict POR, as there are no specific biomarkers known. In this study, we used quantitative proteomic analyses to investigate potential biomarkers that can predict poor response during in vitro fertilization based on follicular fluid samples. A total of 1079 proteins were identified using a high-resolution orbitrap mass spectrometer coupled online to a nanoflow-LC system. It is notable that 65 upregulated and 66 downregulated proteins were found to be functionally enriched in poor responders. We also validated these differentially expressed proteins using a triple-quadrupole mass spectrometer for quantification of targeted proteins. Of the differentially expressed proteins, three proteins (pregnancy zone protein, renin, and sushi repeat-containing protein SRPX) were regarded as statistically significant (p < 0.05).

Reference Values for the Revised Anti-Müllerian Hormone Generation II Assay: Infertile Population-based Study.

Anti-Müllerian hormone (AMH) is now accepted as an important clinical marker of ovarian reserve and is increasingly measured as an initial evaluation at infertility clinics. The aim of this study was to establish reference values for the revised second generation (Gen II) assay using population-based data. In this population-based cohort study, AMH data from unselected infertile women aged 25-45 years from June 2013 to June 2014 (n = 15,801) were collected. The AMH values were measured using the revised Gen II assay. We established and validated 5 AMH-age regression models. Based on the optimal AMH-age model, reference values and centile charts were obtained. The quadratic model (log AMH = 0.410 × age -0.008 × age² -3.791) was the most appropriate for describing the age-dependent decrease in AMH measured using the revised Gen II assay. This is the largest population-based study to establish age-specific reference values of AMH using the revised Gen II assay. These reference values may provide more specific information regarding the ovarian reserve estimation of infertile women.