Hormone Replacement Treatment Research Articles

Aminopeptidase A: A Novel Therapeutic Target for Hypertension Management.

The renin-angiotensin system (RAS) is crucial for regulating and understanding the pathophysiology of hypertension. However, there has been little focus on the breakdown of the active peptide, angiotensin II (AngII). Given that animals lacking aminopeptidase A (APA) exhibit hypertension, it may be concluded that APA is a crucial enzyme in regulating blood pressure by breaking down AngII. It has been also seen that the elevated blood pressure in the spontaneously hypertensive rat (SHR) is caused by the activation of the RAS and a concurrent reduction in renal angiotensin-converting enzyme (ACE) activity. The activity of APA is elevated at the beginning of pre-eclampsia and decreases below the levels seen during a normal pregnancy as pre-eclampsia progresses (particularly, in severe cases). The activity of Serum APA is also heightened after hormone replacement treatment (HRT), perhaps as a response to increasing levels of AngII. Therefore, it is crucial to examine the connection between the activation of the RAS, the levels of AngII in the bloodstream, and the presence of APA in hypertension conditions.

RELATIONSHIP OF THE USE OF SYSTEMIC STEROIDS, HORMONAL REPLACEMENT THERAPY OR ORAL CONTRACEPTIVES WITH THE INCREASE OF DENTAL IMPLANT FAILURE IN WOMEN

Currently, dental implants are proving to be one of the main forms of oral rehabilitation. However, despite the high success rates of dental implants, there are some facts that may end up reducing these and contributing to an increase in failure rates. Especially in female patients, the use of systemic steroids, oral contraceptives and hormone replacement treatment stands out. This work aims to develop an information cluster about the higher rate of dental implant failures in female patients who use systemic steroids and/or oral contraceptives and/or are under hormone replacement therapy, which could serve as a valuable source of information for both dentistry students and professionals in the field. A narrative review of the literature was carried out using as a bibliographical basis scientific articles related to dental implant failures in women who use systemic steroids and/or oral contraceptives and/or undergo hormone replacement therapy, published between the years 2020 and 2024 presented in English available in the online databases BVSalud, Lilacs, Scielo, PUBMed and Google Scholar. After analyzing all the material used as a bibliographical basis for the development of this work, it is concluded that the use of systemic steroids, and/or oral contraceptives and/or hormone replacement therapy can negatively affect dental implants in women and can collaborate with the failure of implants.

Comparison of live birth rates following the transfer of day-6 blastocysts on the 6th versus 7th day of progesterone exposure in hormone replacement treatment–frozen embryo transfer cycles

Objective: The duration of progesterone exposure is critical for establishing and maintaining a pregnancy in hormone replacement treatment (HRT)–frozen embryo transfer (FET) cycles. This study compared the live birth rates (LBRs) of patients undergoing day-6 warmed blastocyst transfer on either the 6th or 7th day of progesterone administration in HRT-FET cycles.Methods: A retrospective cohort study was conducted using data from the central registry of Indira IVF Hospital Private Limited. In total, 2,633 patients who underwent day-6 blastocyst transfer cycles with HRT-FET were identified. The cycles were categorized based on the timing of the day-6 blastocysts transfer: P+6 vs. P+7 (initiation date: P+1). Propensity scores were calculated. The primary outcome measure was the LBR.Results: Following propensity score matching, a total of 1,401 patients were included in the final analysis (P+6: n=1,212; P+7: n=189). The number of previous attempts was significantly higher in the P+6 group, whereas the rate of preimplantation genetic testing for aneuploidy was significantly higher in the P+7 group. The LBRs were 59.2% and 54.5% in the P+6 and P+7 groups, respectively (p=0.21). Multivariate regression analysis revealed that the number of previous in vitro fertilization attempts (odds ratio [OR], 3.246; 95% confidence interval [CI], 2.429 to 4.337; p<0.001), the number of blastocysts transferred (OR, 2.011; 95% CI, 1.461 to 2.768; p<0.01), and endometrial thickness on the day of progesterone initiation (OR, 1.143; 95% CI, 1.022 to 1.28; p=0.02) were independent predictors of live birth.Conclusions: The LBRs were comparable in patients who underwent day-6 warmed blastocyst transfer on day 6 or 7 post-progesterone initiation in HRT-FET cycles.

Considerations in Premature Menopause: A Review.

Premature menopause impacts 1% of women under the age of 40. The women are at risk of premature death, ischemicdisease of the heart, neurological conditions, mood disturbances, psychosexual problems, osteoporosis, and subfertility. There is an imperative for less complicated protocols and enhanced approaches for oocyte donation togetpregnantand achievemotherhood in at-risk women. A review of the pertinent literature on premature ovarian insufficiency and selected references was done.A comprehensive review was undertaken by searching the databases PubMed, Scopus, EMBASE, Web of Science, and Science Direct. Pregnancy in women with prematuremenopause was formerly uncommon, but because ofrecent advances in oocyte donation, women with premature menopause can now aspire to have a child. Hormone replacement treatment is useful in treating the negative effects of premature ovarian insufficiency. Women who experience early menopause are at risk for early mortality, ischemic heart disease, neurological conditions, mood problems, psychosexual disorder, osteoporosis, and subfertility. Public awareness and education are critical tools for saving womenat peril.

Re-evaluating the Relationship between Cosmetic Products and Cancer: An Investigative Review of Paradigms

Abstract: Cosmetics are items that are used to glorify or change facial looks and appearance as well as provide fragrance to the body. Their main aim is to cleanse, beautify, facilitate attractiveness, and change physical looks. Women use many different beauty products, such as skin care, hair, perfume, oral hygiene, and nail care items, which may include harmful substances that are threatening to their health. The controversy around cosmetics and beauty products promoting cancer threat has grown over the previous few years. According to data from the European Cancer Registries, postmenopausal and very young women are now seeing an increase in the occurrence of breast cancer, which is the more frequent form of cancer in women. Genetic predisposition, long-term hormone replacement treatment, and various environmental variables, including air pollution, agrochemicals, alcohol, and specific consumer goods like cosmetic additives, are some of the causes of breast cancer. Additionally, the USFDA made all adverse event reports, including those involving concerns about cosmetics, publicly accessible via the Adverse Event Reporting System (CAERS) of the Centre for Food Safety and Applied Nutrition in 2016. In this period of modernization, CAERS is of limited use since there is a lack of different supporting data, such as demographic information, medical history, or linked product usage, and because the existing data is vulnerable to severe reporting bias. Despite the system's potential to protect the public's health, the database's future usefulness will depend on a wide range of reporting participants, more thorough reporting, and concurrent investments in regulatory science and enhanced molecular techniques.

P-285 Serum progesterone level may not impact ongoing pregnancy rate (OPR) in patients with endometriosis undergoing frozen-warmed-blastocyst transfer employing hormone replacement treatment (HRT) with subcutaneous progesterone

Abstract Study question Do serum progesterone (P4) levels on frozen embryo transfer (FET)-1 day impact OPRs in patients with endometriosis undergoing HRT-FET with subcutaneous progesterone (sc P)? Summary answer In HRT cycles employing sc P, serum P4 levels on FET-1 day do not affect OPRs in patients with or without endometriosis. What is known already In HRT-FET cycles employing vaginal P, reproductive outcomes are improved by serum P4 monitoring and employing a rescue protocol, if needed. However, there is paucity of data for the need of serum P4 monitoring in HRT cycles employing sc P. Endometriosis is associated with P4 resistance. There is only one study evaluating the impact of serum P4 levels on reproductive outcomes in patients with endometriosis; in this study lacking a control group and employing vaginal P gel 90 mg/12 hours supplemented by daily 50 mg intramuscular P, a threshold of 37.1 ng/ml has been reported for improved live birth rates. Study design, size, duration Retrospective cohort study. 451 consecutive patients undergoing their first HRT- vitrified warmed blastocyst transfer during November 2021-June 2023 at Anatolia IVF Centre were included. 44 patients had endometriosis with surgical and/or ultrasound findings and the remaining 407 patients did not harbor endometriosis. The presence of adenomyosis was an exclusion criterion. Following 10-12 days of 6 mg/day estradiol valereate use, sc P 25 mg/12hours (Prolutex, Ibsa) was administered. The primary outcome measure was OPR. Participants/materials, setting, methods Serum P4 levels were measured 4-5 hours after morning administration of sc P on FET-1 day. The impact of serum P4 on OPRs was assessed at various percentiles adjusting for female age, body mass index, prior birth, preimplantation genetic testing for aneuploidy, number/grade of blastocysts transferred. Multivariate regression models were performed in the whole cohort incorporating polynomial P4 terms and endometriosis interactions; optimal model for OPR prediction was selected using the lowest Akaike Information Criteria. Main results and the role of chance Patients with (27/44, 61.4%) and without (214/407, 52.6%) endometriosis had comparable OPRs. In the endometriosis group, the 10th, 50th, and 90th percentiles of serum P4 were 15.6, 25.1, and 35.4 ng/ml, respectively, compared to 14.9, 23.5, and 35.6 ng/ml in the non-endometriosis group. In the endometriosis group, the OPRs were 60.0%, 66.7%, 56.3%, and 60.0% for the <10p, 10-50p, 50-90p, >90p groups, respectively. These figures were 46.3%, 50.3%, 56.8%, and 51.2%, in the non-endometriosis group, respectively. In the endometriosis group, taking the 50-90p group as the reference, the adjusted odds ratios (aORs) for OPR of < 10p, 10-50p, and >90p groups were 1.24 [0.03, 50.45], 1.77 [0.31, 10.24], and 2.08 [0.05, 80.23], respectively. In the non-endometriosis group, the respective aORs were 0.85 [0.40, 1.79], 0.80 [0.49, 1.29], and 0.72 [0.34, 1.50]. In the multivariate regression analysis to determine the optimal model, neither serum P4 levels (aOR for linear term: 1.11 [0.98, 1.26]; for quadratic term: 0.998 [0.996, 1.00]) nor the diagnosis of endometriosis (OR: 1.48 [0.74, 2.98]) significantly predicted ongoing pregnancy after adjusting for confounders. Additionally, the optimal model did not include the interaction term, suggesting that endometriosis does not significantly modify the impact of serum P4 levels on OPRs. Limitations, reasons for caution The study’s limitations include retrospective study design, a limited sample size of the endometriosis cohort, absence of laparoscopy for endometriosis exclusion in the non-endometriosis group, and lack of data on endometriosis phenotypes. Wider implications of the findings In HRT-FET cycles employing sc P 25 mg/12hours neither serum P4 nor the presence of endometriosis have an impact on OPRs. Endometriosis may not modify the impact of serum P4 on OPRs suggesting a lack of P resistance in such cycles or the overcoming of P resistance by this regimen. Trial registration number not applicable

P-643 Menopause should not be considered a confounding factor in endometrial preparation protocol’s comparative clinical trials: a retrospective cohort study with 1.109 euploid single embryo transfers

Abstract Study question Does menopause have an impact on obstetric and perinatal outcomes when performing elective euploid single-blastocyst transfers (eeSBT) in a hormonal replacement treatment (HRT) protocol? Summary answer eeSBT in a non-menopause elective HRT group(eHRT) did not show higher success rates nor better obstetric and perinatal outcomes compared to a menopause HRT group(mHRT). What is known already Menopause has been suggested to be a confounding factor in clinical trials when comparing the results and success rates for endometrial preparation in modified natural cycle (mNC) Vs HRT: including menopause patients could lead to selection bias seen that they can never be included in the mNC group. Few data are available on eeSBT ≥3BB (Gardner score) cryotransfers comparing obstetric and perinatal results between eHRT and mHRT, to have the opportunity to include them all in further comparative trials, with a low bias risk. Study design, size, duration Retrospective single-centre comparative study, including 1.109 eeSBT (≥3BB, Gardner score) between Jan-2018 and Dec-2022: 1.025 (92,4%) in eHRT and 84 (7,6%) in mHRT. The eHRT and mHRT groups were homogeneous for egg donor’s age (29,1±5,9 yo Vs 25,8±4,1 yo) recipient’s age (41,4±4,9 yo Vs 44,9±4,7 yo), body mass index (22,6±4,7 Vs 22,6±5,3) severe male factor (3,5% Vs 3,6%), the need for sperm donation (30,0% Vs 35,7%), and the average throphoectoderm embryo quality (A = 32,5% Vs A = 29,8%). Participants/materials, setting, methods We studied the clinical, obstetric and perinatal outcomes of the 1.109 eeSBT, comparing eHRT and mHRT groups for: pregnancy rate, miscarriage rate, live birth rate, twin pregnancy rate, severe preeclampsia, preterm birth rate (<37, <35, <32 and <28 weeks) and neonatal weight. We used Chi-square test and T-Test to compare groups (p < 0,05). Main results and the role of chance There were no statistically significant differences between eHRT and mHRT groups when comparing pregnancy rates (63,7% Vs 64,3%, p = 0,92), miscarriage rates (15,6% Vs 11,1%, p = 0,053) and live birth rates (44,3% Vs 48,8%, p = 0,42); no significant differences were found in the severe preeclampsia rate(2,0 Vs 1,2, p = 0,84), nor in the twin pregnancy rate (0,9 Vs 2,4, p = 0,34) even if it almost tripled in the mHRT group. Preterm, major and extreme preterm birth rates were comprable between eHRT and mHRT groups: <37 weeks (9,9% Vs 4,9%, p = 0,29) < 35 weeks (3,3% Vs 0, p = 0,23) <32 weeks (1,3% Vs 0, p = 0,46) <28 weeks (0,2% Vs 0, p = 0,76). There were no significant differences in neonatal weight (3292 + 481g Vs 3.135 + 419g, p = 0,052). Limitations, reasons for caution In a preliminary study, we compared and additional 245 eeSBT in mNC with the HRT group, and no significant differences in obstetric or perinatal outcomes were reported when including or excluding the mHRT sub-group. Wider implications of the findings In eeSBT, the eHRT group did not report better obstetric nor perinatal results compared to the mHRT group; further prospective clinical trials comparing mNC Vs HRT should not consider menopause as a major confouding factor, when using eeSBT. Trial registration number Not Applicable

P-653 Impact of dydrogesterone use in cycles with low progesterone levels on the day of frozen embryo transfer

Abstract Study question Assessing if Frozen Embryo Transfer (FET) outcomes in hormonal replacement treatment with dydrogesterone (DYD) for low progesterone levels match those with normal progesterone (P4) values Summary answer The live birth rate showed no significant difference between patients with low and normal serum P4 levels in FET, utilizing DYD as rescue therapy What is known already The number of IVF/ICSI cycles and frozen embryo transfers (FET) is increasing. The preparation for FET can occur in natural or artificial cycles, showing no significant differences in clinical pregnancy and live birth rates. Artificial cycles involve exogenous estradiol supplementation, starting after menses, and progesterone (P4) addition post-endometrial proliferation. Numerous studies consistently indicate that diminished P4 levels are correlated with inferior outcomes in hormonal replacement treatment, showing a potential decrease of up to 30% in ongoing pregnancy rates. Despite a suggested rescue strategy, evidence supporting its efficacy using an oral route is insufficient. Study design, size, duration This was a retrospective cohort study, of single embryo transfers (SET) from FET cycles conducted between July 2019 and March 2022, after artificial endometrial preparation with valerate-estradiol and micronized vaginal P4. In cases of low serum P4 (up to 12,5ng/dl) on the planned transfer day, 10 mg of dydrogesterone (DYD) three times daily was added. Solely blastocyst single embryo transfers (SET) were included. The primary endpoint was the live birth rate> 24 weeks. Participants/materials, setting, methods 535 FET-SET cycles were analyzed. Patients with an endometrial layer thinner than 7 mm, endocavitary pathology or serum P4 values< 4ng/dl were excluded. The explanatory variables evaluated were: relevant female characteristics, previous IVF/ICSI cycle and relevant FET cycle parameters (endometrial thickness, serum P4 value on the FET day, days in culture before blastocyst freezing) and use of DYD as rescue therapy. Statistical analysis was performed using IBM®SPSS® statistics v22.0 and R4.2.2 for Windows. Main results and the role of chance Out of the 535 FET cycles analyzed, 136(25.4%) underwent treatment with DYD. There were 337 pregnancies (63%), 207 live births (38.6%) and 130 miscarriages (38.5%). Serum P4 varied from 4.2-32.3 ng/dl, with an average of 14.93 ng/dl (SD 4.52). The best model to explain serum P4 distribution considered a gamma distribution for P4. Female age on the FET day, female ethnicity and female weight seemed to explain P4 variation. A sensitivity analysis on the P4 values was performed. The data were divided into 5 groups according to P4 levels and the rate of live birth per quintile was evaluated. There were no statistically significant differences between the groups. Patients with low P4 which had DYD added had no statistical differences regarding deliveries, 40% vs 36% (p = 0,354). The multivariable model revealed that older females at pick up, a thinner endometrial measure and transferring a day 6 blastocyst were negativey associated with live birth (p < 0,05), but not P4 levels or medication with DYD. A sub-group analyses was performed according to the median value of P4 (9.6 ng/ml) of those to whom DYD was added. No statistically significant differences were identified for biochemical pregnancy 59% vs 60% (p = 1) and live birth rate 34%vs38% (p = 0,653). Limitations, reasons for caution This retrospective study lacks an untreated control group, causing inherent heterogeneity. It’s unclear if there’s an upper limit for P4 levels to restrict DYD supplementation or a minimum level rendering this strategy unsuitable. Monitoring DYD’s fetal/neonatal safety is imperative. Wider implications of the findings The supplementation with oral DYD in hormonal replacement FET cycles is an easy and cheap strategy in patients with for low P4 levels. The duration of DYD administration should be further evaluated. Trial registration number not applicable

O-208 The Programmed Ovulatory Frozen-Thawed Embryo Transfer Cycle (PO-FET): a suggested FET protocol integrating aspects of embryo transfer scheduling, efficacy optimization and maternal/fetal safety

Abstract Study question What is the effect of 30mg oral dydrogesterone (DYD), given to induce endometrial receptivity in natural-proliferative-phase-FET-cycles (NPP-FET), on ovulation, progesterone and DYD/DHD-levels, respectively, and outcomes? Summary answer Oral DYD 30mg allows scheduling endometrial receptivity in natural cycles while not interfering with ovulation in the vast majority of patients. What is known already Globally, approximately 60% of all ETs are performed after cryopreservation. Hormone Replacement Treatment (HRT)-FET cycle-regimens have come under scrutiny, because of i) risk of insufficient progesterone exposure with conventional dosing-schemes and ii) maternal/fetal risks stemming from the iatrogenic lack of a corpus luteum. Oral DYD 10mg (tid) supposedly does not interfere with ovulation/corpus luteum formation, and does not cross-react with progesterone in ELISA. It could thus be used for inducing endometrial receptivity (scheduling, in a natural cycle, the time point of ET) and luteal phase support, while allowing ovulation dissociated from the window-of-implantation and monitoring of endogenous progesterone serum levels. Study design, size, duration Within a multi-centric, prospective, clinical cohort study (NCT03507673), 559 normally cycling women from the routine care population who underwent FET after IVF/ICSI in a natural cycle (2/2021 – 8/2023) had serum/plasma samples prospectively collected/stored on day of FET for measurement of E2, progesterone and DYD/DHD in Roche Elecsys®-Immunoassay and liquid chromatography/tandem mass spectroscopy (LC-MS/MS), respectively. FET was performed on day 2/3 (cleavage-stage) or day 4/5 (morula/blastocyst) in 17.4% and 82.6% of FETs, respectively. Participants/materials, setting, methods From cycle day 10, women underwent endocrine (E2, LH and P) and sonographic monitoring until E2 >180pg/ml, leading follicle >16mm and endometrial thickness was >6mm. Physicians could then initiate oral DYD10mg (tid) or–in absence of LH rise–postpone initiation, under 2-daily monitoring, to meet the organizational preferences of the patient and/or center (for example, avoiding weekends). FET was performed for day 2 (cleavage), 3, 4 or 5 (blastocyst) on day 3-6 of DYD-intake, respectively. Main results and the role of chance Previously reported PK of 10mg DYD (tid) are confirmed/extended. While log-levels of DYD and DHD were highly correlated (0.95), P-levels were not (0.02, 0.02). In 94.4% of patients, ovulation could be confirmed by serum-P levels on the day of FET or in late luteal phase. Medians (IQR) of DYD and P on day 3 and days 5, respectively, were 0.93ng/ml (0.93ng/ml) and 2.96ng/ml (3.19ng/ml), and 1.13ng/ml (1.09ng/ml) and 8.50ng/ml (4.40ng/ml). Serum-P levels increased with the FET day (medians 2.0, 3.0, 6.6, and 8.5 ng/ml on days 2, 3, 4, and 5) and only very weakly correlated with LH, E2 levels, and follicular diameter at last monitoring. 42.5% and 34.8% of patients had positive hCG and ongoing clinical pregnancy, respectively. Ongoing pregnancy was independent from plasma-DYD levels (< 25th percentile [<0.66 ng/ml] 37.9% vs. ≥25thperc. [≥0.66 ng/ml] 34.3%, RD 1.5%, 95%CI: -16.5% to 17.4%, p = 0.334), yet dependent from serum-P levels (< 25thperc [<4.85 ng/ml] 25.9% vs. ≥25thperc [≥4.85 ng/ml] 35.3%, RD 9.4%, 95% CI 0.4% to 17.6%, p = 0.0161).However, neither of the two serum hormone values is predictive of a dichotomous outcome in isolation, nor do they demonstrate predictive interaction when considered together in logistic regression modelling. Limitations, reasons for caution DYD, like hCG or any other progestin given for LPS, may negatively interfere with LH surge, ovulation and luteal phase characteristics. Controlled studies on different progestin types and doses are necessary to better understand how to optimize luteal phase and thereby optimally support embryo nidation, pregnancy maintenance and maternal/fetal health. Wider implications of the findings The PO-FET protocol induces the implantation window, thus offers (some) flexibility in FET timing, shows little interference with ovulation/corpus luteum formation, provides double gestagenic support with no need for monitoring P or DYD levels, however allows corpus luteum activity monitoring in luteal phase and early pregnancy, is injection-free, and low-cost. Trial registration number NCT03507673

P-403 Does a thick endometrium really matter? It’s impact on FET cycles results

Abstract Study question Does a thick endometrium negatively affect the results of FET cycles after PGT? Summary answer Endometrial thickness above 10mm did not affect pregnancy rates, and live birth rates were even higher in the group with thick endometrium. What is known already The success of an assisted reproduction technique leads on two main points: getting a high-quality embryo and a functional endometrium. The results of the relationship between a thick endometrium and its influence on the pregnancy rates are contradictory till the date, mainly due to the relatively reduced sample sizes and the presence of confoundings. In the same way, they are scarce the papers that analyze the results of FET under hormone replacement therapy in cycles with euploid blastocysts. These cycles could be considered the gold standard to establish the influence of thick endometria in the implantation rate. Study design, size, duration Retrospective study of FET cycles under hormone replacement therapy with transfer of an euploid blastocyst after PGT. Multicentric analyze of cycles performed between 2015 and 2021 in our Spanish IVIRMA clinics. Participants/materials, setting, methods We analyzed 3158 cycles of FET under hormone replacement therapy with transfer of an euploid blastocyst. Hormone therapy consisted in estrogens (etinil estradiol orally or in patches), plus progesterone (400 mg/ 12 hours, vaginally). Two groups were established: an “optimal” endometrial thickness (7 - 10mm) (80.81%), and those with a higher one (19.19%), the day that the transfer was planned. The objective was to analyze the implantation, miscarriage and live birth rates. Main results and the role of chance Both groups were comparable in terms of age, origin an age of the oocytes, origin of the sperm, and serum estradiol levels the day that the embryo transfer was programmed. There were differences in the BMI of the patients (23.00 Vs 23.51, p = 0.004) and the day of the cycle that the embryo transfer was planned (11.8 Vs 11.78, p < 0.001). There were no differences regarding hormonal treatment protocol or dose, nor regarding cycle monitoring. There were not significant differences in the implantation rate between the group with an endometrial thickness between 7 and 10mm (62.84%; CI 95% 60.90 – 64.78) and the one with a thicker endometrium (66.08%; CI 95% 62.19-69.98; p = 0.143). Neither in the miscarriage rate (15.76%, CI 95% 14.36-17.24; Vs 14.40%, CI 95% 11.70-17.46; p = 0.444). Statistically significant differences were found in the live birth rate, which was of 47.74% in the group of endometrial thickness between 7 and 10mm (CI 95% 45.75-49.73), and 53.20% in the group with a thicker endometrium (CI 95% 49.09-57.27, p = 0.019) Taking these results into account, we could conclude that a thick endometrium does not negatively affect the results of FET cycles. Limitations, reasons for caution The nature of our study was retrospective not randomized. It was performed with euploid embryos under hormone replacement treatment. Thus, results may not be applicable in other settings. The measure of the endometrial thickness is very variable between professionals and there can be more factors involved in the functionality. Wider implications of the findings Embryo transfer should not be canceled in cases of endometrial thickness > 10 mm. More studies are needed to ascertain if it would be beneficial to achieve systematically an endometrial thickness > 10 mm Trial registration number Not applicable

1566-P: Growth Hormone Replacement Treatment Improves Nonalcoholic Fatty Liver Disease in Patients with Pituitary Stalk Interruption Syndrome—A Randomized, Single-Blind, Placebo-Controlled Prospective Cohort Study

1566-P: Growth Hormone Replacement Treatment Improves Nonalcoholic Fatty Liver Disease in Patients with Pituitary Stalk Interruption Syndrome—A Randomized, Single-Blind, Placebo-Controlled Prospective Cohort Study

Effect of different endometrial preparation methods on pregnancy outcome of FET in women with a normal menstrual cycle

ABSTRACT Objective: This study aims to explore the relationship between different endometrial preparations and pregnancy outcomes among patients with regular ovulatory cycles in order to find the best endometrial preparation methods in the freeze–thaw embryo transfer (FET) cycle. Materials and Methods: This is a retrospective study to investigate FET pregnancy outcomes in women who had a regular menstrual cycle, were younger than 35 years old, and underwent a modified natural cycle (mNC), ovulation induction (OI), or a hormone replacement treatment (HRT) cycle. A total of 1071 frozen cycles were included for analysis. Results: The implantation rate and live birth rate (LBR) in the OI group show a significant difference when compared to the mNC and HRT groups (P < 0.01). After adjusting for confounding factors, the logistic regression analysis revealed that the number of embryos transferred, the embryo stage, and quality were significantly associated with clinical pregnancy rate and LBR. The LBR was additionally affected by the mode of the endometrial preparation; the OI cycle could increase LBR. Conclusions: Endometrial preparation methods affect the LBR in women with a regular menstrual cycle. The OI cycle had an advantage in the LBR of FET.

Menopausal Hormone Therapy, an Ever-Present Topic: A Pilot Survey about Women's Experience and Medical Doctors' Approach.

Background and Objective: Menopause can be associated with many clinical manifestations: vasomotor symptoms, urogenital problems, and additional psychological disturbances, such as anxiety, mood changes, and sleep alterations. The prolonged lack of hormones also increases the risk of long-term consequences. Hormone Replacement Treatment (HRT) in menopause consists of the administration of estrogen, alone or associated to progesterone, to relieve these uncomfortable disturbances and to prevent the onset of other pathologic conditions. The aim of this study is to examine the prevalence of HRT use in a sample of menopausal women and their experience with menopause and HRT. This study also investigates the knowledge of general practitioners (GPs) and gynecologists about HRT and its prescription. Materials and Methods: We conducted a cross-sectional population survey on 126 women of 50-59 years in an industrial city in the North of Italy, Vercelli (Novara), in Eastern Piedmont. We also presented a questionnaire on the topic to 54 medical doctors (GPs and gynecologists) of the same area. Results: The prevalence of HRT use in our sample was 11.9%. In total, a good percentage of the users affirmed to be satisfied with HRT. Additionally, a minority of women reported being ideally against the use of replacement hormones, were advised against using HRT by doctors, and did not use it because of the fear of side effects. We found a positive association between patient education, health care attitude, and HRT usage. A significant number of women knew about HRT from the media, and most of them were not informed by a health professional. Despite this, the interviewed doctors considered their knowledge about HRT as 'good' and would recommend HRT: only 5.6% would not prescribe it. Conclusions: Our results highlight the need for information about HRT among patients and health professionals, along with the need for more effective communication, evaluation, and suggestion of treatment.

Impact of dydrogesterone use in cycles with low progesterone levels on the day of frozen embryo transfer.

This study aims to evaluate whether the clinical outcomes of cycles with frozen embryo transfer (FET) in hormonal replacement treatment supplemented with dydrogesterone (DYD) following detection of low circulating levels of progesterone (P4) were comparable to the results of cycles with otherwise normal serum P4 values. Extended analyses of a retrospective cohort that included FET cycles performed between July 2019 and March 2022 after a cycle of artificial endometrial preparation using valerate-estradiol and micronized vaginal P4 (400mg twice daily). Whenever the serum P4 value was considered low on the morning of the planned transfer, 10mg of DYD three times a day was added as a supplement. Only single-embryo transfers of a blastocyst were considered. The primary endpoint was live birth rate. Five-hundred thirty-five FET cycles were analyzed, of which 136 (25.4%) underwent treatment with DYD. There were 337 pregnancies (63%), 207 live births (38.6%), and 130 miscarriages (38.5%). The P4 values could be modeled by a gamma distribution, with a mean of 14.5ng/ml and a standard deviation of 1.95ng/ml. The variables female age on the day of FET, ethnicity, and weight were associated with a variation in the serum P4 values. There were no differences in the results between cycles with or without the indication for DYD supplementation. Live birth rate did not vary significantly in females with low and normal serum P4 levels on the day of FET when DYD was used as rescue therapy.

Unusual coexistence of restrictive heart disease and Kallmann syndrome: a case report

BackgroundKallmann–Morsier syndrome is a rare disease characterized by the association of congenital gonadotropic deficiency and anosmia or hyposmia. The cardiac manifestations associated with this syndrome are little known. Through this case, we will characterize the cardiac involvement of this disease in the light of what is already described in the literature.Case presentationWe report the case of a young patient who presented with a picture of cardiac decompensation revealing restrictive heart disease. In her exploration, she was found to have primary amenorrhea, leading to the diagnosis of Kallmann syndrome. Medical treatment was optimized for the management of her cardiac decompensation as well as hormonal replacement treatment for her delayed puberty and growth.ConclusionsCardiac manifestations in Kallmann–Morsier syndrome are few reported in the literature, and restrictive heart disease is uncommon with no cases report till now. This association suggests a possible common genetic origin that should be explored in the future.

Dynamic changes in AI-based analysis of endometrial cellular composition: Analysis of PCOS and RIF endometrium

BackgroundThe human endometrium undergoes a monthly cycle of tissue growth and degeneration. During the mid-secretory phase, the endometrium establishes an optimal niche for embryo implantation by regulating cellular composition (e.g., epithelial and stromal cells) and differentiation. Impaired endometrial development observed in conditions such as polycystic ovary syndrome (PCOS) and recurrent implantation failure (RIF) contributes to infertility. Surprisingly, despite the importance of the endometrial lining properly developing prior to pregnancy, precise measures of endometrial cellular composition in these two infertility-associated conditions are entirely lacking. Additionally, current methods for measuring the epithelial and stromal area have limitations, including intra- and inter-observer variability and efficiency. MethodsWe utilized a deep-learning artificial intelligence (AI) model, created on a cloud-based platform and developed in our previous study. The AI model underwent training to segment both areas populated by epithelial and stromal endometrial cells. During the training step, a total of 28.36 mm2 areas were annotated, comprising 2.56 mm2 of epithelium and 24.87 mm2 of stroma. Two experienced pathologists validated the performance of the AI model. 73 endometrial samples from healthy control women were included in the sample set to establish cycle phase-dependent dynamics of the endometrial epithelial-to-stroma ratio from the proliferative (PE) to secretory (SE) phases. In addition, 91 samples from PCOS cases, accounting for the presence or absence of ovulation and representing all menstrual cycle phases, and 29 samples from RIF patients on day 5 after progesterone administration in the hormone replacement treatment cycle were also included and analyzed in terms of cellular composition. ResultsOur AI model exhibited reliable and reproducible performance in delineating epithelial and stromal compartments, achieving an accuracy of 92.40% and 99.23%, respectively. Moreover, the performance of the AI model was comparable to the pathologists’ assessment, with F1 scores exceeding 82% for the epithelium and >96% for the stroma. Next, we compared the endometrial epithelial-to-stromal ratio during the menstrual cycle in women with PCOS and in relation to endometrial receptivity status in RIF patients. The ovulatory PCOS endometrium exhibited epithelial cell proportions similar to those of control and healthy women’s samples in every cycle phase, from the PE to the late SE, correlating with progesterone levels (control SE, r2 = 0.64, FDR < 0.001; PCOS SE, r2 = 0.52, FDR < 0.001). The mid-SE endometrium showed the highest epithelial percentage compared to both the early and late SE endometrium in both healthy women and PCOS patients. Anovulatory PCOS cases showed epithelial cellular fractions comparable to those of PCOS cases in the PE (Anovulatory, 14.54%; PCOS PE, 15.56%, p = 1.00). We did not observe significant differences in the epithelial-to-stroma ratio in the hormone-induced endometrium in RIF patients with different receptivity statuses. ConclusionThe AI model rapidly and accurately identifies endometrial histology features by calculating areas occupied by epithelial and stromal cells. The AI model demonstrates changes in epithelial cellular proportions according to the menstrual cycle phase and reveals no changes in epithelial cellular proportions based on PCOS and RIF conditions. In conclusion, the AI model can potentially improve endometrial histology assessment by accelerating the analysis of the cellular composition of the tissue and by ensuring maximal objectivity for research and clinical purposes.

Effect of GnRH agonist down-regulation combined with hormone replacement treatment on reproductive outcomes of frozen blastocyst transfer cycles in women of different ages.

To investigate the effect of GnRH agonist (GnRH-a) down-regulation prior to hormone replacement treatment (HRT) to prepare the endometrium in frozen embryo transfer (FET) cycles in women of different ages. This was a retrospective study, and after excluding patients with adenomyosis, endometriosis, severe endometrial adhesions, polycystic ovary syndrome (PCOS), and repeated embryo implantation failures, a total of 4,091 HRT cycles were collected. Patients were divided into group A (<35 years old) and group B (≥35 years old), and each group was further divided into HRT and GnRHa-HRT groups. The clinical outcomes were compared between groups. There was no statistically significant difference in clinical outcomes between the HRT and GnRHa-HRT groups among women aged <35 years. In women of advanced age, higher rates of clinical pregnancy and live birth were seen in the GnRHa-HRT group. Logistic regression analysis showed that female age and number of embryos transferred influenced the live birth rate in FET cycles, and in women aged ≥ 35 years, the use of GnRH-a down-regulation prior to HRT improved pregnancy outcomes. In elderly woman without adenomyosis, endometriosis, PCOS, severe uterine adhesions, and RIF, hormone replacement treatment with GnRH agonist for pituitary suppression can improve the live birth rate of FET cycles.

Primary ovarian insufficiency- An overview: Part 2 diagnosis and management

Loss of normal ovarian function before the age of 40 characterizes primary ovarian insufficiency (POI), sometimes called premature ovarian failure or early menopause. Many women all around the globe deal with this serious reproductive health issue. The purpose of this study is to provide a broad perspective on how to identify and treat primary ovarian insufficiency. Clinical symptoms, hormone profiles, and ovarian imaging all play a role in making a diagnosis of POI. Genetic predisposition, autoimmune disease, and medical intervention are all possible origins. Counseling and treatment techniques for afflicted women can only be used when a timely and correct diagnosis has been made. Hormone replacement treatment (HRT) for symptom alleviation, avoidance of long-term consequences including osteoporosis and cardiovascular disease, and preservation of fertility are all part of the management of postmenopausal irritability (POI). To reduce the severity of menopausal symptoms and safeguard bone health, oestrogen replacement treatment is needed. HRT selection should be patient-specific, taking into account factors like as age, co-morbidities, and individual preferences. If a young woman is diagnosed with POI and she wants to have children in the future, she and her doctor should talk about fertility preservation strategies such oocyte or ovarian tissue cryopreservation. The latest treatments and possible revolutionary methods to POI management are also discussed in this overview. Stem cell therapy, ovarian tissue transplantation, and hormone manipulation are all examples of such unproven methods. While these treatments are still in their infancy, they show promise for the future of POI management. In conclusion, this review article gives a comprehensive, up-to-date explanation of how primary ovarian insufficiency is diagnosed and treated. Early detection, proper counselling, and individualised treatment plans are emphasised for afflicted females. The reproductive and overall health results of these people may be improved with a deeper knowledge of the processes producing POI and the development of more effective medicines.

CSIG-29. CLINICAL AND TRANSCRIPTOMIC DATASET IDENTIFIES LARGE CHANGES IN IMMUNE AND HORMONAL SIGNALING AMONGST RECURRENT PATIENTS WITH CRANIOPHARYNGIOMA

Abstract INTRODUCTION Craniopharyngioma is a low-grade suprasellar brain tumor that often produces deficiencies of pituitary hormones, including growth hormone. Although epidemiological data are reassuring that growth hormone does not lead to craniopharyngioma recurrence, the theoretical risk is cause for concern. To address this and other questions related to the care of individuals with recurrent craniopharyngioma, we analyzed gene expression in craniopharyngiomas in the context of clinical data. We envision insights that could guide decisions about hormone replacement and tumor-focused treatment alternatives. METHODS Clinical information was abstracted for a cohort of individuals diagnosed with craniopharyngioma at the Children’s Hospital of Philadelphia between 2016 - 2020. In parallel, tumor transcriptomic data for patients with craniopharyngioma were collected from the Children’s Brain Tumor Network (CBTN) and matched to clinical data where applicable. Bulk RNA-sequencing analysis, pathway analysis, and immune deconvolution (xCell) of samples was performed in R to identify transcript-level changes that distinguish recurrent from initial craniopharyngioma. RESULTS CBTN data was available for 54 initial tumor samples and 17 recurrent tumor samples, with matched clinical data available for 33 samples (26 initial, 7 recurrent). We did not find differences in clinical characteristics between individuals with versus without recurrence. Pathway analysis notably suggested altered levels of antigen presentation (NES: 2.97), Programmed cell death (NES: 2.34), WNT signaling (NES: 1.97), and Growth Hormone Signaling (NES: -1.277) amongst recurrent samples when compared against initial samples. Deconvolution of samples showed altered levels of M2-like macrophages (39.2% increased) and CD4+ T-helper-2 cells (-54.7% decreased) in recurrent samples compared against initial samples. Preliminary work is being completed to frame these results in the context of available clinical neuroendocrine data. CONCLUSION This work highlights marked changes in immune and hormonal signaling in samples from recurrent craniopharyngioma tumors. These insights have potential therapeutic implications that deserve further investigation.

Hysteroscopic Endometrial Fundal Incision in Oocyte Recipients before Embryo Transfer May Improve Reproductive Outcomes: A Prospective Study.

Induced endometrial injury is a technique described that have positive impact on implantation. The aim of this study was to investigate whether hysteroscopic endometrial fundal incision (EFI) in oocyte recipients before embryo transfer increases pregnancy and live birth rates or not. A prospective study was conducted between 2014 and 2019 at an in vitro fertilization (IVF) unit in Greece. As part of the protocol, hysteroscopy and EFI were offered to all the egg recipients and the outcomes compared with those from an older cohort from the same Unit not undergoing hysteroscopy. In total, 332 egg recipients participated in the study; 114 of them underwent EFI prior to embryo transfer. Both groups were similar in terms of age, years of infertility, duration of hormone replacement treatment (HRT) and number of blastocysts transferred. In the EFI group, minor anomalies were detected and treated in 6.1% (n=7) of the participants. Moreover, pregnancy test was positive in 73.7% of the women in the hysteroscopy group compared to 57.8% in the nonhysteroscopy group (P=0.004). Live birth rate was also higher (56.1 vs. 42.2%, P=0.016) in the EFI group compared to the non-hysteroscopy one. Apart from the obvious benefit of recognizing obscured anomalies, requiring surgical correction, it appears that in oocyte recipients prior to embryo transfer, EFI might improve uterine receptivity and reproductive outcomes.