Hormone Replacement Therapy Group Research Articles

Effect of Hormone Replacement Therapy on Chronic Rhinosinusitis Management.

To investigate whether hormone replacement therapy (HRT) impacts health care resource utilization in the management of chronic rhinosinusitis (CRS) in older women. Using the TriNetX US health record database, women 55 years or older with a diagnosis of CRS were included and followed for 3 years. The cohort was stratified into two groups: women who received HRT at the beginning of the study were compared to women who did not receive HRT. The groups were matched by age, race, ethnicity, history of asthma, and history of nasal polyps. Outcomes included whether the patient underwent endoscopic sinus surgery (ESS) and frequency of antibiotic use. Measures of association, Kaplan-Meier analysis, and cohort descriptive statistics were calculated. Of the 65,400 women included, the mean age was 66.9 years. 27.0% and 3.6% of patients had a history of asthma or nasal polyps, respectively. Overall, 2.0% of CRS patients underwent ESS, with the HRT group less likely to undergo ESS [OR: 0.28; 95% CI: (0.25-0.32)] compared to patients who did not receive HRT. When stratified by polyp status, HRT patients with nasal polyps had a greater decrease in ESS rates compared to control than HRT patients without nasal polyps. The HRT group had a higher mean number of antibiotic prescriptions compared to the non-HRT group. HRT is associated with decreased utilization of ESS to treat CRS, with a greater effect size for ESS among CRSwNP patients. However, HRT was associated with higher antibiotic utilization. Level 3 Laryngoscope, 2024.

Cardiovasculoprotective Effects of Estrogen and its Use as Hormonal Replacement Therapy

Epidemiologic studies have shown that the incidence of cardiovascular disease is closely related to gender. This is because endogenous estrogens have broad effects on the circulatory system, leading to the hypothesis that estrogens are cardiovascular protective, underlying their use as hormone replacement therapy (HRT) to reduce the incidence of cardiovascular disease. However, large prospective clinical trials (HERS and WHI) do not support this. This review aims to better understand the cardiovascularoprotective effects of estrogen and answer the question of whether estrogen can be used as hormonal replacement therapy in post-menopausal women to prevent cardiovascular events by incorporating data from the most recent prospective clinical trial, the KEEPS study. HERS and WHI reported no reduction in cardiovascular events in postmenopausal women using HRT, even showing an increased risk of thromboembolism. This study was criticized because participants had been menopausal for 12 years, so the KEEPS study was conducted with participants within three years of menopause, with the result that there was no significant reduction in the progression of atherosclerosis between the HRT group and the placebo group. The KEEPS study states that HRT is safe, and no thromboembolic events were found. Although endogenous estrogen has cardiovascular protective effects, estrogen hormone therapy cannot reduce cardiovascular events in postmenopausal women despite metabolic improvements and beneficial effects such as improvement of postmenopausal-related symptoms, maintaining bone density, and improving sexual function.

Hormone replacement therapy and periodontitis progression in postmenopausal women: A prospective cohort study.

This study aimed to investigate the responses of periodontal environment to hormone replacement therapy (HRT) in postmenopausal women with or without periodontitis. HRT is a common and effective strategy for controlling menopausal symptoms, while the changes of periodontal environment under it, particularly in postmenopausal women with periodontitis, remain unclear. As a prospective cohort study, a total of 97 postmenopausal women receiving HRT were screened, including 47 with and 50 without periodontitis. Correspondingly, 97 women did not receiving HRT were screened as controls during the same period. The full-mouth sulcus bleeding index (SBI), bleeding on probing (BOP), probing pocket depth (PPD), and clinical attachment level (CAL) were measured using periodontal probes. The levels of interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α) in the gingival crevicular fluid were measured using enzyme-linked immunosorbent assay. In addition, cone beam computed tomography was performed to measure the alveolar bone height (ABH) and bone mineral density (BMD). In postmenopausal women without periodontitis, no significantly changes on periodontal parameters were observed after HRT. In women with stage II periodontitis, SBI, BOP, IL-6, and TNF-α were significant decreased after one year and two years of HRT. Compared to the controls, women with stage II periodontitis who underwent HRT had significantly lower CAL and ABH and higher BMD in the second year. The incidence of at least one site with CAL increase ≥1 mm between baseline and 2 years was significantly lower in the HRT group than in the control group in women with stage II periodontitis. In addition, HRT was significantly associated with a decrease in SBI, BOP, IL-6, and TNF-α in the first year and with a decrease in CAL, SBI, BOP, IL-6, and ABH and an increase in BMD in the second year. In postmenopausal women with stage II periodontitis, HRT is associated with the alleviation of inflammation within two years and the remission of alveolar bone loss in the second year. HRT appears to decrease the incidence of CAL increase ≥1 mm within 2 years in women with periodontitis by inhibiting inflammation and alveolar bone loss.

Hormone Replacement Therapy and Risks of Various Cancers in Postmenopausal Women with De Novo or a History of Endometriosis.

This study examined the impact of hormone replacement therapy (HRT) on the occurrence of various cancers in postmenopausal women with de novo or a history of endometriosis. In the datasets for ten cancers (cervical, uterine, ovarian, breast, colon, gastric, liver, lung, pancreatic, and thyroid), women who received HRT (the HRT group) and those who did not (the control group) were selected by a 1:1 matching with those who met the study criteria. In the dataset for each cancer, the incidence of each cancer was very low (0.2% to 1.5% in the HRT group and 0.2% to 1.3% in the control group). The duration of HRT was 1.3 ± 2.1 years. After adjusting for co-variables, HRT was a significant risk factor for uterine cancer (p < 0.05). However, the risk of liver cancer decreased significantly with duration of HRT (p < 0.05). Moreover, combined estrogen and progesterone decreased the risks of liver and thyroid cancers significantly (p < 0.05), and estrogen alone decreased the risks of breast and lung cancers significantly (p < 0.05). Tibolone was not associated with the risk of any of the cancers assessed. These results can help guide the use of HRT in women with de novo or a history of endometriosis.

Exploring the Association Between Age Groups and Success Patterns in Platelet-Rich Plasma Therapy: A Cohort Study.

Objective This study aimed to comprehensively examine the correlation between success trends in platelet-rich plasma (PRP) therapy and the advancing age of patients undergoing fertility interventions. Methods Female participants were categorized randomly into five age groups undergoing PRP or conventional hormone replacement therapy. Procedures included controlled ovarian stimulation, escalating estrogen dosage, gonadotrophin injections, and embryo transfer post-ovulation trigger. A pivotal PRP intervention was provided to half of the age sub-groups, and endometrial thickness was assessed 24 hours prior to embryo transfer. Statistical analysis employed SPSS 26.0 for Windows Student Version (IBM Inc., Armonk, New York), incorporating descriptive statistics, one-way analysis of variance (ANOVA), Tukey's honestly significant difference (HSD) testto explore age-PRP success relationships (p<0.05). Results The study, involving 60 participants, revealed a balanced patient distribution across age groups, with 20-30 age groups contributing 23.33% each. Baseline characteristics showed no significant differences between PRP and hormone replacement therapy (HRT) groups. Post-intervention, PRP demonstrated consistently higher endometrial thickness (p<0.001) and clinical pregnancy rates (63.33%) compared to HRT (40%). These findings suggest a positive association between PRP therapy and improved outcomes, particularly in younger age cohorts. Conclusion The study challenges traditional perspectives on hormonal influences in fertility, highlighting a potential link between PRP therapy and favorable outcomes among younger age groups. Improved endometrial thickness and clinical pregnancy rates in the PRP group emphasize the need for further exploration of PRP's mechanisms and applications in reproductive medicine.

Factors associated with low bone mineral density in Turner syndrome: a multicenter prospective observational study.

Turner syndrome (TS) is associated with a high risk of fracture due to low bone mineral density (BMD). While hypogonadism is known to play a role in decreasing BMD, other factors have not been studied well. Focusing on diet, exercise, and bone metabolism markers, the present, multicentric, prospective, observational study aimed to identify factors contributing to decreased BMD in TS. In total, 48 patients with TS aged between 5 and 49 years comprising a pre-pubertal group (n = 9), a cyclical menstruation group (n = 6), and a hormone replacement therapy (HRT) group (n = 33) were enrolled. The cyclical menstruation group and the HRT group were referred to collectively as the post-pubertal group. The bone mineral apparent density (BMAD) Z-score was higher in the pre-pubertal group than in the post-pubertal group (-0.3 SD vs. -1.8 SD; p = 0.014). Within the post-pubertal group, the median BMAD Z-score was -0.2 SD in the cyclical menstruation group and -2.3 SD in the HRT group (p = 0.016). Spearman's rank correlation revealed no correlation between the BMAD Z-score and bone metabolism markers. No significant relationship was observed between the BMAD Z-score and either the vitamin D sufficiency rate or the step sufficiency rate. A negative correlation was found between BMAD Z-score and serum sclerostin in the pre-pubertal group and serum FSH in the post-pubertal group. In conclusion, the present study found no relationship between the vertebral BMAD Z-score and diet or exercise habits in TS, indicating that estrogen deficiency is the chief reason for low BMD in TS.

Pregnancy outcomes of 4 endometrial preparation protocols in adenomyosis patients with thin endometrium during frozen embryo transfer: a retrospective cohort study

Introduction: This study aimed to compare the pregnancy outcomes of different endometrial preparation protocols in patients with adenomyosis and thin endometrium during frozen embryo transfer. Methods: The study, which was conducted at the Reproductive Hospital Affiliated to Shandong University, included 236 patients with adenomyosis and thin endometrium who underwent frozen embryo transfer between January 1, 2011, and December 12, 2022. The pregnancy outcomes and maternal and infant complications among the 4 groups were further compared. Results: These patients with adenomyosis and thin endometrium were divided into 4 groups based on the endometrial preparation protocols used: natural cycle treatment (n=53), hormone replacement therapy group (n=73), gonadotropin-releasing hormone agonists + hormone replacement therapy group (n=49), and ovarian induction group (n=61). The demographic, cycle, and embryologic characteristics were similar between groups. The livebirth rates (P=0.29), full-term pregnancy rates (P=0.55), preterm pregnancy rates (P=0.33), clinical pregnancy rates (P=0.77), biochemical pregnancy miscarriage rates (P=0.28), early miscarriage rates (P=0.16), and late miscarriage rates (P=0.69) were comparable among 4 groups. In addition, there were no significant differences in maternal and infant complications. Conclusion: The pregnancy outcomes of frozen-embryo transfer among 4 endometrial preparation protocols in patients with adenomyosis and thin endometrium were comparable, indicating no significant disparities. In addition, no noteworthy variations were observed in terms of maternal and infant complications in these patients.

Pretreatment with long-acting gonadotropin-releasing hormone agonists improved pregnancy outcomes after hysteroscopic multiple polypectomies: A retrospective study of 660 frozen–thawed embryo transfer cycles

ObjectiveTo compare the reproductive pregnancy outcomes of pretreatment with long-acting gonadotropin-releasing hormone agonist (GnRH-a) plus hormone replacement therapy (HRT) with HRT-only cycles, and investigate differences between single polypectomy and multiple polypectomies, and between one or two doses of GnRH-a. Materials and methodsThis was a retrospective cohort study on patients undergoing polypectomy who underwent frozen–thawed embryo transfer (FET) from March 2018 to May 2019. They were divided into GnRH-a pretreatment and HRT-only groups. Each group was divided into single polypectomy or multiple polypectomies (in a single hysteroscopic session) subgroups. Clinical pregnancy rate and live birth rate (LBR) were the main outcomes. The effect of GnRH-a dosage was further analysed. ResultsThere were 212 GnRH-a pretreatment cases (45 single and 167 multiple polyps) and 448 HRT-only cases (228 single and 220 multiple polyps). The LBR of the GnRH-a pretreatment group (53.3%) was significantly higher than the HRT group (43.3%; P = 0.016). Logistic regression analysis showed that GnRH-a pretreatment significantly affected the LBR (odds ratio, OR 1.470, 95% confidence interval, Cl 1.046–2.065; P = 0.026). In the multiple polypectomy subgroup, the LBR with GnRH-a pretreatment was higher than with HRT-only (54.5% vs 43.6%; P = 0.034). However, the LBR was not different between the respective single polypectomy subgroups (48.9% vs 43.0%; P = 0.466). For patients with multiple polyps, two GnRH-a pretreatments produced a higher LBR than a single GnRH-a pretreatment (62.7% vs 47.8%), but without significant difference (P = 0.055). ConclusionGnRH-a pretreatment improved the LBR for FET cycles after hysteroscopic multiple polypectomies, independent of dose.

Effect of tibolone versus hormone replacement therapy on lower urinary tract symptoms and sexual function

BackgroundFew studies have compared the effects of tibolone versus hormone replacement therapy (HRT) on lower urinary tract symptoms and female sexual function. The current study aimed to compare these treatments. MethodsWomen with climacteric symptoms were recruited consecutively and allocated to receive tibolone (2.5 mg) or estradiol valerate (1 mg) and medroxyprogesterone acetate (2.5 mg). Patients were followed up at 4 weeks and 12 weeks after treatment. ResultsOverall, there were no significance of improvement in the International Prostate Symptoms Score (IPSS) scores in the HRT group. However, nocturia and the IPSS storage score improved after tibolone treatment. In addition, orgasm, satisfaction and pain improved after HRT. However, desire, lubrication, and Female Sexual Function Index (FSFI) total scores improved after tibolone treatment. There was a between-group difference in the change from baseline in the nocturia score after 4 weeks of treatment (0.1 ± 0.9 for HRT vs. −0.4 ± 1.2 for tibolone, p = 0.02). Nonetheless, there were no significant differences of the changes from baseline in the other IPSS and FSFI domains between the tibolone and HRT groups. ConclusionDespite the limited effect, tibolone seems to have more benefit in nocturia than HRT. In addition, tibolone seems to have benefits on overall low urinary tract storage symptoms; and both tibolone and HRT seem to have beneficial effects on female sexual function, despite there were no significant differences between tibolone and HRT.

Association between endometrial thickness and birthweight of singletons from vitrified-warmed cycles: a retrospective cohort study

Research questionWhat is the association between endometrial thickness (EMT) and the birthweight of singleton infants born from frozen-thawed embryo transfer cycles? DesignThis retrospective cohort study was conducted from January 2016 to December 2019. Participants were categorized into a natural cycle (NC, n = 8132) group and hormone replacement therapy (HRT, n = 4975) group. Only singleton deliveries were included. The primary outcomes were measures of birthweight and relative indexes. Multivariable logistic regression and multivariable-adjusted linear regression models that incorporated restricted cubic splines were used. ResultsIn the HRT group, the risk of delivering a small for gestational age (SGA) infant was increased in women with an EMT <8.0 mm (adjusted odds ratio [aOR] 1.85, 95% confidence interval [CI] 1.17–2.91) compared with women with an EMT of 8.0 to <12.0 mm, and increased with an EMT ≥12.0 mm (aOR 1.85, 95% CI 1.03–3.33). An inverted U-shaped relationship was found between EMT and birthweight in women with HRT. No significant differences were shown in birthweight z-score, or being SGA or large for gestational age, in singletons among the three EMT groups in the natural cycles. ConclusionsA thinner endometrium seen in women undergoing HRT cycles was associated with a lower birthweight z-score, as well as a higher risk of SGA. However, no significant association was observed between EMT and birthweight z-score or SGA in the NC group. It is noteworthy that a thicker endometrium was not associated with a higher birthweight in frozen-thawed embryo transfer (FET) cycles. Women with a thin endometrium who achieve pregnancy require specialized attention, particularly if they are undergoing FET with HRT cycles.

The effects of different endometrial preparation regimens on pregnancy outcomes in frozen-thawed embryo transfer cycles: a prospective randomized controlled study

Objective An increasing number of research have emerged to compare the pregnancy outcomes between the natural cycle and the hormone replacement therapy (HRT) cycle in preparing the endometrium for frozen-thawed embryo transfer (FET), but the results are controversial. This prospective randomized controlled study was hence designed to obtain more solid evidence. Materials and methods In this study, patients with regular menstrual cycle length (21–35 days) who underwent FET between January 2010 to December 2017 were recruited for this study. Upon further filtering with the selection criteria of patients being, a total of 405 patients were recruited and randomized. Finally, analysis was performed on 384 patients: 178 belonged to the natural cycle group whereas the remaining 206 were in the HRT group. The primary outcome was live birth rate, while the secondary outcomes were implantation rate, clinical pregnancy rate, early miscarriage rate, late miscarriage rate, multiple birth rate and low birth weight rate. Results The live birth rate (37.6% vs 30.1%, p = 0.119) of natural cycle group were higher than those of the hormone replacement therapy group, although the difference was not significant. The secondary outcomes were not found to differ significantly between the two groups. Nonetheless, the endometrium was found to be thicker in the natural cycle group (10.75 mm) than the HRT group (9.00 mm) (p < 0.001). Conclusion No significant differences were observed between the pregnancy outcomes of the natural cycle group and the HRT group which comprised of patients with regular menstrual cycle length.

Letrozole use in vitrified single-blastocyst transfer cycles is associated with lower risk of large for gestational age infants in patients with polycystic ovary syndrome.

To evaluate the obstetric and perinatal outcomes of three routine endometrial preparation protocols in women with PCOS who underwent frozen embryo transfer (FET). This was a retrospective study in women with PCOS who underwent FET in an academic reproductive medical center. A total of 2710 cycles were enrolled and classified into three groups according to different endometrial preparation protocols; human menopausal gonadotropin (HMG), letrozole + HMG, or hormone replacement therapy (HRT). The stimulation groups had reduced risks of hypertensive disorders of pregnancy (HDP), large for gestational age (LGA) infants, and cesarean delivery than the HRT group. After adjustment for different confounder combinations in the two models, the frequencies of LGA and HDP in the letrozole + HMG group and the HMG group were still significantly lower than those in the HRT group. The letrozole + HMG group exhibited a reduced risk of LGA than HMG group after adjustment of confounders. A trend toward risk reductions in HDP and LGA was observe in turns of HRT, HMG, and letrozole + HMG groups, and the trends were statistically significant (Ptrend = 0.031 and 0.001). In patients with PCOS, ovarian stimulation protocols for endometrial preparation are associated with reduced risks of HDP and LGA compared to HRT cycles. The use of letrozole could further reduce risk of LGA compared to HMG only protocol. We propose that ovarian stimulation protocols can be used widely for endometrial preparation in FET cycles in women with PCOS, especially with the use of letrozole.

The natural cycle protocol of endometrial preparation for frozen embryo transfer decreases the miscarriage rate in women with recurrent pregnancy loss

Objective To investigate whether different endometrial preparation methods lead to different results. Design Retrospective cohort study. Patients Women with recurrent pregnancy loss undergoing frozen embryo transfer (FET). Interventions Natural cycle (NC) protocol (n = 111) with no drug or human chorionic gonadotropin (HCG) used for endometrial preparation, vs. the hormone replacement therapy (HRT) protocol (n = 797) with estrogen or gonadotropin releasing hormone agonist (GnRH-a) plus estrogen used for endometrial preparation. Main outcome measures Miscarriage rate and live birth rate (LBR). Results Compared to women in the HRT protocol, women undergoing NCs had fewer previous FET cycles, lower antral follicle counts (AFCs), fewer oocytes retrieved and a thicker endometrium on the day of progesterone administration. Women in the HRT group had a higher miscarriage rate (29.4% vs. 17.2%) and a lower LBR (37% vs. 46.9%) than the rates of women in the NC group. Univariate analysis showed that female age also had a negative association with the miscarriage rate. Logistic regression indicated that endometrial preparation using the NC protocol was linked to a decreased likelihood of miscarriage. Conclusions The NC protocol decreased the miscarriage rate and increased the LBR for patients with recurrent pregnancy loss compared with the HRT protocol.

Effect of tamoxifen in patients with thin endometrium who underwent frozen-thawed embryo transfer cycles: a retrospective study.

Thin endometrium leads to an impaired implantation rate. The aim of the study is to compare the clinical outcomes of tamoxifen (TAM) and hormone replacement therapy (HRT) used in patients with thin endometrium (<7mm) in frozen-thawed embryo transfer (FET)cycles. A total of 176 FET cycles with thin endometrium were retrospectively analyzed in our center from Jan 2020 to May 2022. According to patients' own will, 112 patients were allocated to the HRT group and 64 patients chose the TAM protocol. Clinical outcomes were compared between two groups. The duration of treatment was shorter in the TAM group(12.03±2.34d) than the HRT group (16.07±2.52 d), which was statistically different (p<0.05). The endometrial thickness on the transfer day of the TAM group (7.32±1.28 mm) was significantly thicker than that of the HRT group (6.85±0.89mm, p<0.05). The clinical pregnancy rate of the TAM group (50.0%) was higher than that of the HRT group (36.6%), but there was no significant difference (p >0.05). The early miscarriage rate was significantly lower in the TAM group compared with the HRT group (5.9% Vs 26.8%, adjusted OR 0.10, p<0.05), while the live birth rate was higher in the TAM group (46.9% Vs 26.8%, adjusted OR 2.24, p<0.05) compared with the HRT group. For patients with thin endometrium, TAM effectively improved the endometrial thickness and increased the live birth rate. TAM can be used as an alternative protocol for patients with thin endometrium.

Pregnancy outcomes in women with adenomyosis, undergoing artificial endometrial preparation with and without gonadotropin-releasing hormone agonist pretreatment in frozen embryo transfer cycles: An RCT.

Selecting a suitable and preferable method for endometrial preparation in frozen embryo transfer (FET) cycles for women with adenomyosis is still challenging in infertility treatment. To compare 2 artificial endometrial preparation regimens with and without gonadotropin-releasing hormone agonist (GnRHa) pretreatment in women with adenomyosis undergoing FET cycles. This randomized clinical trial study was conducted on 140 adenomyosis cases who underwent FET cycles at Arash Women's hospital, Tehran, Iran from May 2020 to March 2021. Participants were randomly allocated into hormonal replacement therapy (HRT) and HRT+GnRHa pretreatment groups (n = 70/each). Endometrial preparation with 2-6 mg daily estradiol was started in the HRT+GnRHa group, taking after down-regulation with the GnRHa. Within the HRT group, the same dose of estradiol was commenced within the early follicular stage. The main (chemical and clinical pregnancy rates) and auxiliary results (twin pregnancy, miscarriage, and live birth rates) were compared between groups. The demographic characteristics and severity of adenomyosis, endometrial thickness, and pattern at starting progesterone administration were similar in the 2 groups, and triple-line endometrium was found to be the dominant pattern in both groups (p = 0.65). No significant differences were observed in chemical, clinical, and twin pregnancy rates as well as miscarriage and live birth rates between groups (p = 0.71, p = 0.81, p = 0.11, and p = 0.84, respectively). However, the total estrogen dose and duration of estrogen consumption were significantly higher in the pretreatment group (p = 0.001, and p = 0.003). These results indicated that the hormonal endometrial preparation with estrogen and progestin for FET cycles is as efficacious as a protocol involving preceding pituitary suppression with a GnRHa. Further large randomized clinical studies are required to confirm these findings.

P-109 Letrozole versus hormone replacement therapy for frozen embryo transfer: A randomized clinical trial

Abstract Study question Do the outcomes of frozen embryo transfer cycles differ according to endometrial preparation (EP) with letrozole versus hormone replacement therapy (HRT)? Summary answer Letrozole seems to be as effective as HRT preparation in frozen cycles in terms of treatment outcomes. What is known already Vitrification improved the survival of vitrified-warmed embryos and increased the number of FET cycles. A common EP strategy for FET includes augmentation of the endometrium using estrogen followed by progesterone supplements. Retrospective studies have shown that using aromatase inhibitors (letrozole) in FET cycles was associated with higher clinical pregnancy and live birth rates, with a lower miscarriage rate, as compared to HRT cycles. Letrozole maintains regular feedback mechanisms, facilitating normal follicular growth, and promotes single follicle development and ovulation. Moreover, it does not have any negative effects on the endometrium and can improve endometrial receptivity. Study design, size, duration This randomized controlled trial was performed in two university-affiliated medical centers. A total of 170 patients undergoing frozen embryo transfer cycles from June 2018 to June 2021 were eligible. Participants/materials, setting, methods Patients were randomized to either letrozole (n = 69) or HRT protocol (n = 101) for EP, using a blocked randomization method. Inclusion criteria were single blastocyst transfer with normal uterine cavity. Exclusion criteria were patients older than 40 years, oocyte donation cycles, or more than 3 previous transfers without a pregnancy. The primary study outcome was percentage of clinical pregnancies, defined as clinical pregnancies/embryo transfers, excluding canceled treatments. Main results and the role of chance The characteristics of the study groups were comparable in age, BMI, gravidity, parity, previous treatment history and characteristics of the relevant fresh cycle in which the embryo was frozen. After excluding 5 cancelled treatments in the letrozole group and 2 in the HRT group, the percentage of clinical pregnancies between the letrozole and HRT arms were similar (24 (38.0%) versus 34 (34.6%), respectively, p = 0.67). There was no difference in the percentages of live births (22 (34.9%) versus 28 (28.6%), respectively, p = 0.4) or missed abortions (1 (4.1%) versus 5 (14.7%), p = 0.19). For patients who did not achieve pregnancy in the randomized treatment cycle, we retrospectively examined the outcome of the next treatment cycle with the other EP protocol, when possible. Achievement of a clinical pregnancy was the same for change in treatment for both study groups (7(50%) in the letrozole group and 9(50%) in the HRT group). Limitations, reasons for caution Limitations of this study included the heterogeneous study groups. Even though class II ovulation disorders were similar in prevalence in both groups, they included different indications for ART. Pregnancy complications were not evaluated and should be further investigated in a study with a larger sample size. Wider implications of the findings Letrozole seems to be as effective as HRT for EP in frozen cycles, with possible advantages of fewer missed abortions and pregnancy complications. Letrozole could be a suitable option for EP, as it is effective and, enables more convenient timing, versus natural FET. Trial registration number NCT03540979

P-357 Downregulation (DR) with combined gonadotropin-releasing hormone agonist (GnRHa) and aromatase inhibitor (AI) optimizes the frozen-thawed embryo transfer (FET) results in women with adenomyosis

Abstract Study question Does combined GnRHa &amp; AI therapy for downregulation in women with adenomyosis optimize the FET success rates / outcomes on par with women without adenomyosis? Summary answer GnRHa combined with AI used for downregulation in women with adenomyosis optimized the outcomes of frozen–thawed embryo transfer cycle on par with women without adenomyosis. What is known already Women with adenomyosis have lower rates of successful implantation via altered molecular expressions in the endometrium due to local hyperestrogenism &amp; also an increased risk of early pregnancy loss (Munro et al 2019). DR improves the clinical pregnancy rate by reducing the endometrial inflammatory reaction and/or myometrial contractility and their impact on uterine receptivity in women with adenomyosis undergoing FET (Sania Latif et al 2021). Combined treatment for uterine adenomyosis with Anastrazole plus GnRHa showed better results than dienogest treatment with a higher reduction of symptoms &amp; higher pregnancy rates (M Sbracia &amp; F Scarpellini, 2018). Study design, size, duration A Retrospective cohort study conducted at a tertiary care fertility unit. Data for 326 women with/without adenomyosis undergoing frozen–thawed embryo transfer after IVF was was retrieved from the hospital's database and analyzed for a period between September 2021 to November 2022. Participants/materials, setting, methods Women with adenomyosis (n = 107) received Anastrozole 1mg/day for 2months plus 3doses of Inj. Goserelin 3.6mg subcutaneously at 28days interval between 2successive doses. Hormone replacement therapy (HRT) was started 2weeks after the 3rddose of Inj. Goserelin &amp; FET was performed after an optimum endometrial thickness (EMT) was achieved. For women without adenomyosis (n = 219) HRT was started on cycle Day-2 &amp; FET was performed after achieving an optimum EMT. Serum beta-hCG was performed on Day15 after FET. Main results and the role of chance Statistical analysis was performed using SPSS20version. Normally distributed continuous variables were compared using a student t-test, and categorical variables were compared by χ2 and Fisher's exact test, where appropriate. To reduce selection bias, propensity score matching was used, and propensity matching yielded 99 pairs. Baseline characters like age (p-value=0.36), BMI (p-value=0.12), duration (p-value=0.28), type (p-value=1) &amp; cause (p-value=0.3) of infertility, endometrial thickness (p-value=0.37), day of embryo transfer (p-value=0.57) were comparable for the two groups. FET results in terms of positive pregnancy test (Serum beta-hCG &amp;gt; 50mIU/ml) were found to be 68.21% for the DR- FET group and 67.71% for the HRT group which were comparable(p-value=0.17). This suggests that downregulation in women with adenomyosis helps achieve success rates similar to women without the disease. Pregnancy outcomes like miscarriage (15 vs 13.13 %, p-value=1.00), biochemical pregnancy (3.03 vs 2.02 %, p-value=1.00) and ectopic pregnancy (1.01 vs 0 %, p-value=0.49) rates analyzed between the DR FET and HRT groups showed no statistically significant difference. Clinical pregnancy rates were almost similar for the 2 groups (55.71 Vs 57.46%, p-value=0.65). Thus, we conclude that downregulation with combined GnRHa and AI optimizes the frozen-thawed embryo transfer results in women with adenomyosis on par with women without adenomyosis. Limitations, reasons for caution This is a retrospective study and hence randomized comparison was not possible. Women were followed up for 12 weeks of pregnancy, hence live birth rates were not analyzed in our study. Wider implications of the findings Combining the two treatment modalities (GnRHa + AI) which work at different sites optimizes IVF success rates &amp; pregnancy outcomes. Hence we suggest that well-designed prospective randomized studies are needed to further analyze the synergistic role of this drug combination for downregulation in women with varied severity of adenomyosis. Trial registration number Not applicable

O-022 Shall we go “natural” for endometrial preparation in egg donation programs? Live birth rates and obstetrical outcome from 797 frozen single-blastocyst transfers cycles

Abstract Study question Frozen single blastocyst transfer in modified natural cycle (mNC) increases success rates reducing obstetric risks in egg recipients, compared to Hormone Replacement Therapy (HRT) protocols? Summary answer In egg recipients, single-blastocyst transfer in mNC showed higher pregnancy rates, lower miscarriage rates, higher new-born rates compared to HRT, being preterm birth rate comparable. What is known already When choosing endometrial preparation protocols for egg recipients, we must consider medication safety and costs, cycle’s cancellation rate, clinical outcomes as maternal and fetal risks. The superiority of mNC over HRT for frozen embryo transfers (FET) has been reported in terms of delivery and miscarriage rates as well as obstetrical complications, but few data are available on egg recipients, being HRT protocols the routine treatment in most cases. In donor programs, when a blastocyst freeze-all strategy or egg banking is applied, there is no longer need for donor-recipient synchronization and many FET could be performed in mNC cycles. Study design, size, duration Retrospective single-centre comparative clinical study, including 797 frozen single-blastocyst transfer (FSBT) initiated cycles between January 2020 and December 2021: 590 (74%) in HRT protocol and 207 (26%) in mNC protocol. The two groups were homogeneous for donor’s age (25,4 yo HRT Vs 25,8 yo mNC), recipient’s age (42,1 yo HRT Vs 42,4 yo mNC), severe male factor (6% HRT Vs 4% mNC), and the need for a sperm donor (28% HRT Vs 22% mNC). Participants/materials, setting, methods Among 797 started cycles, we compared cancellation rates between HRT and mNC groups due to either medical reasons (inadequate endometrium, bleeding, ovulatory leak) or other issues (no embryo survival, flight cancellations, COVID-19 restrictions). We studied the clinical outcomes of the 683 FSBT performed, comparing HRT and mNC cycles for pregnancy rate, clinical pregnancy rate, miscarriage rate, live birth rate, and preterm birth rate &amp;lt;35 weeks. We used Chi-square test to compare groups (p &amp;lt; 0,05). Main results and the role of chance CANCELLATION RATES: Out of the 797 endometrial preparation cycles started, the overall cancellation rate was 14% from which 72,8% due to medical reasons (inadequate endometrium, bleeding, ovulatory leak) and 27,2% due to other issues (no embryo survival, SARS-Cov-2 related issues, flight cancellations, etc.); when evaluating cancellation for medical reasons, we didn’t find significant differences between HRT protocol cycles (9%) and mNC protocol cycles (7%), p = 0,33. CLINICAL OUTCOMES: Out of the 683 frozen single blastocyst transfers performed, no twin pregnancies occurred as expected. There were no statistically significant differences between HRT Vs mNC endometrial preparation protocol when comparing pregnancy rates (59% Vs 63%, p = 0,35), clinical pregnancy rates (49% Vs 57%, p = 0,10) and miscarriage rates (19% Vs 16%, p = 0,48). Live birth rate was significantly higher in the mNC (47%) compared to HRT (38%), p = 0,046. Overall preterm birth rate &amp;lt;35 weeks was 3,9%, including &amp;lt;32 weeks 1,1% and &amp;lt;28 weeks 0,3%. There were no significant differences between HRT and mNC endometrial preparation protocol for preterm birth rate &amp;lt;35 weeks (3,6% Vs 4,6%, p = 0,75). Limitations, reasons for caution Single-centre retrospective comparative trial. Homogeneity studies included several confounding variables, but other bias could have been studied such as uterine factor, PGT-A rate or previous fertility treatments. Wider implications of the findings In donor programs, the use of modified natural cycle should be encouraged as first option irrespectively from recipient’s age for FET in normo-ovulatory patients, considering the increased live birth rates when compared to HRT-FET cycles. Moreover, mNC cycles are more patient’s friendly and cost-effective. Trial registration number not applicable

Reading skills in males with 47,XXY: Risk factors and the influence of hormonal replacement therapy (HRT)

Purpose47,XXY is often associated with reduced expressive language and literacy skills. This retrospective cross-sectional study investigated risk factors (hormone replacement deficiency, pre-or postnatal diagnosis, and history of family learning disabilities [FLDs]) associated with reading skills in 152 males. MethodsWe analyzed Woodcock Reading Mastery Test scores among 7 prenatally diagnosed male hormone replacement therapy (HRT) groups using analysis of variance along with analysis of variance and 2 postnatally diagnosed male HRT groups (No-T and T) using t tests. Treated prenatally diagnosed males with FLDs were compared with an identically treated prenatal HRT group with no history of FLDs using a t test. ResultsIn prenatally diagnosed males, significant treatment differences were observed on several reading scales (eg, total reading: χ2 = 17.96, P = .006), in which the highest modality HRT group (mean [M] =119.87) outperformed the untreated group (M = 99.88). In the postnatal analysis, we observed a significant effect of treatment on basic skills (P = .01). Despite equal HRT status, males with FLDs (M = 105.79) exhibited reduced total reading skills compared with those in the no FLD group (P = 0.0006). ConclusionOur findings in this pilot study reveal that the most optimal reading trajectory is associated with a prenatal diagnosis, absence of FLDs, and the highest modality HRT.

Hormone replacement therapy and cancer risks in perimenopausal women: A retrospective cohort study using a Japanese claims database.

Hormone replacement therapy (HRT) relieves menopausal syndromes but concerns regarding certain cancer risks remain. This study aimed to investigate cancer risks in perimenopausal women using HRT. Using a health care database in Japan, we compared breast cancer and other cancer risks in perimenopausal women who started HRT between January 2011 and October 2021 at age 45-54 years with that of women who did not use HRT. Women in the control group were selected by 1:4 exact matching on birth year, and followed from the same index time as their counterparts. Data from 12 207 women in the exposure group and 48 828 age-matched women in the control group were analyzed. The median HRT duration was 16.1 (interquartile range, 9.9-28.0) months. Breast cancer risk was lower in the HRT group (adjusted hazard ratio [HR], 0.67; 95% confidence interval [CI], 0.54-0.82). When stratified by age, breast cancer risk was lower in the HRT group who started HRT at age 45-49 years (adjusted HR, 0.54; 95% CI, 0.40-0.72). Estrogen-major HRT accounted for approximately one-third of HRT and uterine corpus cancer risk was increased in estrogen-major HRT (adjusted HR, 2.44; 95% CI, 1.56-3.81). Breast cancer risk in women starting HRT between 45 and 49 years is lower than that in the average population; this finding might be susceptible to unmeasured factors such as early menopause among HRT recipients. Unopposed estrogen therapy accounts for considerable proportion of HRT in Japan and it increases uterine corpus cancer.