Endometrial thickness is an independent risk factor of hypertensive disorders of pregnancy: a retrospective study of 13,458 patients in frozen-thawed embryo transfers.

BACKGROUND: Hypertensive disorders of pregnancy (HDP) are an important cause of maternal and fetal mortality, and its potential risk factors are still being explored. Endometrial thickness (EMT), as one of the important monitoring indicators of endometrial receptivity, has been confirmed to be related to the incidence of HDP in fresh embryo transfer. Our study was designed to investigate whether endometrial thickness is associated with the risk of hypertensive disorders of pregnancy in frozen-thawed embryo transfer (FET). METHODS: This respective cohort study enrolled 13,458 women who received vitrified embryo transfer and had a singleton delivery in the Reproductive Hospital affiliated to Shandong University from January 2015 to December 2019. We set strict screening criteria and obtained the information from the hospital electronic medical system. Statistical methods including logistic regression analysis, receiver operating characteristic curve and restricted cubic spline were used to evaluate the relationship between endometrial thickness and the incidence of pregnancy-induced hypertension. RESULTS: The incidences of HDP in a thin endometrial thickness group (< 0.8 cm) and a thick endometrial thickness group (> 1.2 cm) were significantly greater than in a reference group (0.8 cm-1.2 cm) (7.98 and 5.24% vs 4.59%, P <  0.001). A nonlinear relationship between endometrial thickness and risk of hypertensive disorders of pregnancy was examined by restricted cubic spline (P <  0.001). The thin endometrial thickness and thick endometrial thickness groups were significantly associated with the risk of HDP after adjusting for confounding variables by stepwise logistic regression analysis. Subsequently, subgroup logistic regression analysis based on endometrial preparation regimens showed that thin endometria were still significantly associated with a higher morbidity rate in the artificial cycle group, while in the natural cycle group, thick endometria were closely associated with increased morbidity. CONCLUSION: Our study manifested that both the thin and thick endometria were associated with an increased risk of hypertensive disorders of pregnancy in frozen embryo transfer cycles. Reproductive clinicians should focus on adjusting endometrial thickness in different preparation regimens; and obstetricians should be mindful of the risk of hypertension during pregnancy, when women with thin (< 0.8 cm) or excessively thicker (> 1.2 cm) endometrial thickness achieve pregnancy through frozen-thawed embryo transfer.

Basal Anti Mullerian hormone levels and endometrial thickness at midcycle can predict the outcome after clomiphene citrate stimulation in anovulatory women with PCOS, a retrospective study.

PURPOSE: Recent studies reported that in polycystic ovary syndrome (PCOS) patients, other stimulation agents are superior to the popular first-line regimen, clomiphene citrate (CC) for ovarian stimulation. Nonetheless, CC is still widely used since it is not clear which patients will not respond to it. Furthermore, the prognostic value of endometrium thickness at midcycle is controversial. We aimed to find factors predicting the response to CC and the prognostic value of endometrial thickness at midcycle. METHODS: We collected data retrospectively from 89 anovulatory PCOS patients who had the first stimulation with 50 mg CC. We analyzed the basal levels of AMH, testosterone, LH, LH:FSH ratio and the endometrial thickness at midcycle by univariate, followed by multivariate regression. The outcome measures were pregnancy, follicle maturation and endometrial thickness at midcycle. RESULTS: Stimulation with 50 mg CC resulted in follicle maturation in 50.6% of the women and in 27.0% pregnancies. In the univariate analysis, greater endometrial thickness, lower LH and AMH levels and a lower LH:FSH ratio were associated with pregnancy (p < 0.05). In the multivariate analysis, only endometrial thickness remained predictive (p = 0.045). The endometrial thickness cutoff level of ≥ 8 mm showed a sensitivity of 87.5% (96% CI 67.6-97.3) and a specificity of 66.7% (95% CI 43.0-85.4) for prediction of pregnancy. In the multivariate analysis AMH levels 5.4 (3.4; 7.0) (ng/mL) predicted pregnancy (ß = - 0.194 ± 0.092; p = 0.034) CONCLUSION: We suggest to refrain from CC as first-line regimen in patients with AMH > 7 ng/ml. Under CC treatment, the cutoff value of ≥ 8 mm endometrium thickness at midcycle is associated with a better outcome.

Endometrium development patterns and BMI groups among in vitro fertilization patients; prognostic aspects.

Introduction: The impact of the obesity pandemic on female reproductive capability is a factor that needs to be investigated. In addition, the link between endometrial thickness and in vitro fertilization (IVF) outcomes is contentious. Goal: Our goal was to analyze the association among endometrium development, hormone levels, embryo quality, clinical pregnancy, anamnestic parameters, and body mass index (BMI) in women receiving IVF treatment. Patients and methods: 537 participants undergoing IVF/ICSI cycles with successful oocyte retrieval were enrolled. Subjects were divided into four BMI based groups: underweight (UW; n=32), normal weight (NW; n=324), overweight (OW; n= 115), obesity (OB; n=66). Anthropometric and anamnestic parameters, characteristics of stimulation, endometrial thickness on the day of hCG injection, at puncture, at embryo transfer, FSH, LH, AMH, partner's age and the semen analysis indicators, embryo quality, clinical pregnancy, were recorded and analyzed. Support Vector Machine (SVM) was built to predict potential pregnancies based on medical data using 22 dimensions. Results: In accordance with BMI categories, when examining pregnant/non-pregnant division, the average age of pregnant women was significantly lower in the UW (30.9 ± 4.48 vs. 35.3 ± 5.49 years, p=0.022), NW (34.2 ± 4.25 vs. 36.3 ± 4.84 years, p<0.001), and OW (33.8 ± 4.89 vs. 36.3 ± 5.31 years, p=0.009) groups. Considering FSH, LH, and AMH levels in each BMI category, a statistically significant difference was observed only in the NW category FSH was significantly lower (7.8 ± 2.99 vs. 8.6 ± 3.50 IU/L, p=0.032) and AMH (2.87 ± 2.40 vs. 2.28 ± 2.01 pmol/L, p=0.021) was higher in pregnant women. There were no further statistically significant differences observed between the pregnant and non-pregnant groups across any BMI categories, especially concerning endometrial development. Surprisingly, BMI and weight correlated negatively with FSH (r=-0.252, p<0.001; r=-0.206, p<0.001, respectively) and LH (r= -0.213, p<0.001; r= -0.195, p<0.001) in the whole population. SVM model average accuracy on predictions was 61.71%. Discussion: A convincing correlation between endometrial thickness development and patients' BMI could not be substantiated. However, FSH and LH levels exhibited a surprising decreasing trend with increasing BMI, supporting the evolutionary selective role of nutritional status. Our SVM model outperforms previous models; however, to confidently predict the outcome of embryo transfer, further optimization is necessary.

Enhancing Fertility: A Case Report of the Frozen Platelet-Rich Plasma Therapy for Thin Endometrium and Poor Ovarian Reserve.

A 33-year-old female patient was assessed for primary infertility due to thin endometrium and poor ovarian reserve (POR). The effectiveness of platelet-rich plasma (PRP) therapy was evaluated in terms of thickening the endometrium and enhancing implantation. The patient also had a history of four intrauterine inseminations and one intracytoplasmic sperm injection (ICSI), along with low anti-Müllerian hormone (AMH) and high follicle-stimulating hormone levels which showed POR. Gonadotropins are given to enhance follicular growth, while agonists and antagonists are given to prevent premature luteinizing hormone surge and suppress the top axis. During the first oocyte pick-up (OPU), five oocytes were retrieved. ICSI was done to make fertilization easier. On day 5, the embryos had degraded from their initial high quality. The patient was advised to undergo treatment with PRP. The endometrial thickness was significantly thicker, raising the chance of implantation. The second OPU was scheduled, resulting in the retrieval of 14 oocytes on the same day ICSI was performed. High-quality blastocysts (4AA) were produced and transferred during embryo transfer, and the patient tolerated the procedure well. The clinical success of the pregnancy outcome was confirmed by another beta-human chorionic gonadotropin test.

Ultrasonographic patterns of different regions of uterus according to pregnancy in cows and heifers.

This study aimed to detect pregnancy within the first 20 days after artificial insemination by evaluating the ultrasonographic patterns of the different regions of uterus in Holstein heifers and cows. Animals were divided into subgroups according to pregnancy on 28th day as pregnant (heifer, n: 15; cow, n: 15) and non-pregnant (heifer, n: 15; cow, n: 15). Images were taken from the ovulation-side cornu uteri (OSC), non-ovulation-side cornu uteri (NOSC), and the corpus uteri (CU) on alternate days from D0 to D20. The images were evaluated by ImageJ software in terms of mean gray value (MGV), homogeneity (HOM), and contrast (CON) and endometrium thickness (ET). The mean MGV and G*T and P*T interactions, the mean CON and G*T and G*P interactions, the mean HOM and G*P interactions, and the mean ET and G*P interactions were statistically significant (p < 0.05). In receiver operating characteristic analyses, D2-D6 for CON and D2, D6, D8, D16, and D20 for HOM of OSC in cows and D8 and D10 MGV and D18 and D20 ET of OSC in heifers had high relationship with positive pregnancy (p < 0.05). The use of echogenicity evaluations and endometrium thickness measurements in reproductive management seems to be suitable for the prediction of pregnancy in cows and heifers.

Evaluation of the Association of Endometrial Thickness, Insulin Resistance, and Menstrual Patterns in Adolescent Females with Polycystic Ovarian Syndrome.

STUDY OBJECTIVE: To evaluate endometrial stripe (EMS) thickness and its association with menstrual pattern and insulin resistance in adolescent females with or at risk for polycystic ovarian syndrome (PCOS) METHODS: This was a retrospective case-control study of adolescent females ranging between 12 and 21 years old evaluated in the Adolescent Gynecology & Endocrinology Clinic (AGEC) at a tertiary children's hospital between 2017 and 2021. Transabdominal pelvic ultrasound (US) was obtained for evaluation of PCOS or acute pelvic pain. Unadjusted comparisons were performed between imaging measurements in the PCOS and control (girls without PCOS with acute pelvic pain) groups, as well as analysis of the PCOS group adjusted for age, body mass index, race, and biochemical values. This study was approved by the Institutional Review Board. RESULTS: In our study, 54 subjects met the inclusion criteria for the PCOS group and 42 for the control group. EMS thickness was thinner in the PCOS group than in the control (0.55 ± 0.31 cm vs 0.70 ± 0.23 cm; P < .001). There was no difference in EMS thickness in the PCOS group when stratified by intermenstrual interval, insulin resistance, and other biochemical factors. CONCLUSION: Our findings support recommendations by the 2018 International Guidelines to avoid use of US for the establishment of PCOS diagnosis in adolescents. These results highlight the unique pathophysiology of adolescent PCOS in contrast to PCOS in adult women. Further large-scale prospective studies are needed to understand the role of EMS thickness as a prognostic marker in adolescent PCOS.

Intrauterine instillation of autologous platelet-rich plasma in infertile females with thin endometrium undergoing intrauterine insemination: an open-label randomized controlled trial.

BACKGROUND: Thin endometrium in infertile female patients has always been a clinical challenge for the treating reproductive physicians. OBJECTIVE: This study aimed to evaluate the effect of intrauterine instillation of autologous platelet-rich plasma on endometrial thickness and vascularity in infertile female patients with thin endometrium undergoing ovarian stimulation with intrauterine insemination. STUDY DESIGN: This prospective randomized control study included 120 women undergoing ovarian stimulation with intrauterine insemination, aged between 21 and 37 years, with persistent thin endometrium (<7 mm) on ≥1 cycle in previous ovarian stimulation cycles, even after conventional treatment with estradiol valerate. The women were randomly assigned to study group A and control group B. Baseline endometrial thickness and endometrial vascularity were noted. Intrauterine instillation of autologous platelet-rich plasma was done on the day of trigger in group A, whereas estradiol valerate was given in group B. Another evaluation of endometrial parameters was done on the day of intrauterine insemination. The cycle was repeated for 3 cycles or until the pregnancy was achieved, whichever occurred earlier. Parameters were noted for both groups. Primary outcomes were the change in endometrial thickness and endometrial vascularity. Secondary outcomes were positive pregnancy rate and clinical pregnancy rate. RESULTS: In group A, mean pre-platelet-rich plasma endometrial thickness was 4.66±0.79 mm, which significantly increased to 7.47±0.85 mm after platelet-rich plasma instillation (P<.05) after 3 cycles. This increase was significantly greater than that observed in group B. There was significant increase in endometrial vascularity in group A compared with group B (P<.05). The positive pregnancy rate and clinical pregnancy rate in group A were 23.73% and 18.64%, respectively, and significantly higher than those in group B. CONCLUSION: Autologous platelet-rich plasma is a promising, easily procurable, and novel option for management of infertile females with thin endometrium not responding to conventional treatment. Using it in intrauterine insemination cycles can reduce costs and psychological burden of this subgroup of women by reducing the need for resorting to advanced options such as in vitro fertilization and surrogacy.

The importance of the junctional zone of the endometrium in human reproduction.

Junctional zone endometrium (JZE) thickness and contractility seem to determine gamete and embryo transportation and implantation. Proper function depends on concentration levels, mode and timing of oestrogen and progesterone production. Most probably, the remodelling of spiral arteries, and the development of endometrium and decidua are also highly dependent on JZE activity. Fibroids that are adjacent to JZE affect JZE contractility contributing to abnormal or failed implantation. Disruption of the JZE continuity provokes adenomyosis, a condition that causes chronic inflammation and fibrosis, which negatively affects the normal function of JZE. Imaging by magnetic resonance imaging and three-dimensional sonography can diagnose JZE abnormal appearance, alterations in thickening and contractility frequency, usually in the advanced stage of the disease. Failures of assisted reproduction, and adverse early pregnancy outcomes have also been associated with abnormal JZE. Altered uterine contractions due to JZE changes are strongly associated with poor reproductive outcome and early pregnancy loss. Endometriosis and adenomyosis prevalently co-exist, with clear relation and negative effects on the JZE. The presence of endometriosis should alert to the possibility of coexisting adenomyosis. Co-existence of endometriosis may mask the extent of the negative impact of adenomyosis in infertility.

Efficient Production of Murine Uterine Damage Model.

BACKGROUND: Thin or damaged endometrium causes uterine factor-derived infertility resulting in a failure of embryonic implantation. Regeneration of endometrium is a major issue in gynecology and reproductive medicine. Various types of cells and scaffolds were studied to establish an effective therapeutic strategy. For this type of investigations, production of optimal animal models is indispensable. In this study, we tried to establish various murine uterine damage models and compared their features. METHODS: Three to ten-week-old C57BL/6 female mice were anesthetized using isoflurane. Chemical and mechanical methods using ethanol (EtOH) at 70 or 100% and copper scraper were compared to determine the most efficient condition. Damage of uterine tissue was induced either by vaginal or dorsal surgical approach. After 7-10 days, gross and microscopic morphology, safety and efficiency were compared among the groups. RESULTS: Both chemical and mechanical methods resulted in thinner endometrium and reduced number of glands. Gross morphology assessment revealed that the damaged regions of uteri showed various shapes including shrinkage or cystic dilatation of uterine horns. The duration of anesthesia significantly affected recovery after procedure. Uterine damage was most effectively induced by dorsal approach using 100% EtOH treatment compared to mechanical methods. CONCLUSION: Taken together, murine uterine damage models were most successfully established by chemical treatment. This production protocols could be applied further to larger animals such as non-human primate.

Ideal embryo transfer position and endometrial thickness in IVF embryo transfer treatment.

OBJECTIVE: To establish an ideal transfer strategy by investigating the relationships among embryo transfer (ET) depth, endometrial thickness, and subsequent in vitro fertilization treatment clinical pregnancy outcomes. METHODS: In the present retrospective analysis, data from in vitro fertilization-ET treatment cycles conducted at a fertility center in Shanghai, China, between October 2014 and March 2015 were analyzed. Women were divided into groups 1-4 according to transfer depth (<10; 10-15, 15-20, and >20 mm, respectively), as measured by air bubbles. Additionally, 391 women were divided into groups A-C according to endometrial thickness (<7, 1-12, and >12 mm, respectively). Clinical pregnancy outcomes were assessed by group. RESULTS: Data from 501 cycles were included. Clinical pregnancy and live delivery rates were significantly higher in group 2 (P=0.009 and P=0.002, respectively) and group 3 (P=0.008 and P=0.001, respectively) than in group 4. Among the 394 patients with endometrial thickness data available, clinical pregnancy and live delivery rates were higher in group B (P=0.028 and P=0.015, respectively) and group (P=0.013 and P=0.013, respectively) than in group A. CONCLUSION: Correct transfer depth and endometrial thickness can increase the rates of clinical pregnancy, implantation, and live delivery. Placing the embryos at 10-20 mm from the fundus and at an endometrial thickness of more than 7 mm is recommended for optimal clinical pregnancy outcomes.

Effect of autologous platelet-rich plasma treatment on patients with thin endometrium / Efecto del tratamiento con plasma autólogo rico en plaquetas en pacientes con endometrio delgado

ABSTRACT Introduction: The success of frozen embryo transfer cycles depends on a delicate interaction between embryo quality and endometrium. Low pregnancy rates are associated with a thin endometrium. Objective: To evaluate the effect of autologous platelet-rich plasma treatment on patients with thin endometrium. Methods: In 34 patients with thin endometrium (< 7 mm), canceled in the previous frozen embryo transfer cycles, autologous platelet-rich plasma was prepared, from autologous peripheral vein blood; intrauterine infusion was given during hormone replacement therapy in frozen embryo transfer cycles. Frozen embryo transfer was performed when the endometrium thickness reached ≥ 7mm. Results: Six patients canceled the embryo transfer cycle due to endometrium thickness did not reach 7 mm; 28 patients got endometrial thickness ≥ 7 mm and performed frozen embryo transfer. The endometrial thickness was 7.5 ± 0.8 mm, which was significantly thicker than in the previous cycles (5.6 ± 0.79 mm) with p< 0.002, the implantation rate was 23.07 %, and the clinical pregnancy rate was 12/28 (42.8 %). Conclusion: Autologous platelet-rich plasma improves the endometrial thickness and the pregnancy rate outcomes in women with thin endometrium.

RESUMEN Introducción: El éxito de los ciclos de transferencia de embriones congelados depende de una delicada interacción entre la calidad del embrión y el endometrio. Las bajas tasas de embarazo están asociadas con un endometrio delgado. Objetivo: Evaluar el efecto del tratamiento con plasma rico en plaquetas autólogo en pacientes con endometrial delgado. Métodos: En 34 pacientes con endometrio delgado (< 7 mm) canceladas en los ciclos previos de transferencia de embriones congelados, se preparó plasma autólogo rico en plaquetas, a partir de sangre autóloga de venas periféricas; la infusión intrauterina se administró durante la terapia de reemplazo hormonal en los ciclos de transferencia de embriones congelados. La transferencia de embriones congelados se realizó cuando el grosor del endometrio alcanzó ≥ 7 mm. Resultados: En 6s pacientes se canceló el ciclo de transferencia embrionaria debido a que el grosor del endometrio no alcanzó los 7 mm; 28 pacientes obtuvieron un grosor endometrial ≥ 7 mm y realizaron transferencia de embriones congelados. El grosor del endometrio fue de 7,5 ± 0,8 mm, significativamente mayor que en los ciclos anteriores (5,6 ± 0,79 mm) con p< 0,002; la tasa de implantación fue de 23,07 % y la tasa de embarazo clínico fue de 12/28 (42,8 %). Conclusión: El plasma autólogo rico en plaquetas mejora el grosor endometrial y los resultados de la tasa de embarazo en mujeres con endometrio delgado.

Success in pregnancy through intrauterine insemination at first cycle in 300 infertile couples: an analysis.

OBJECTIVE: The aim of this article was to determine digital levels of the association of factors of pregnancy success after the first cycle of intrauterine insemination (IUI) with 300 infertile couples. METHODS: The IUI procedure was followed at 36 h after triggering the ovulation, if at least one follicle measured >15 mm. Endometrium thickness (ET) and serum luteinizing hormone (LH) levels were measured at day 10 for each patient. The post-wash total motile fraction (TMF) of semen of the partner of each patient was also evaluated. The principal component analysis (PCA) was done with the data to quantify the associations of related factors. RESULTS: The clinical pregnancy rate of first cycle IUI attempts was 17.3 %, observed in females, aged 20-39 years and men with TMF >5 million spermatozoa. The ovarian stimulation enabled the development of follicles measuring >16 mm, with LH levels <10 mIU/L and ET >5 mm for success. The PCA revealed that with the female-age parameter, three factors, NF, ET, and LH were related in the component 1; similarly, NF, LH, and RFS were related in component 2; age, NF, ET, LH, LFS, and TMF were related in component 3; and NF, ET, LH, RFS, and LFS in component 4 were related, i.e., the best correlation. CONCLUSIONS: Associated principal determinative factors, LH, female-age, NF and LFS values were highly significant, but the factors, ET, RFS and TMF were statistically insignificant for success through IUI in pregnancy.