Hormone Replacement Treatment Research Articles

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.

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.

Case report: neuropsychological assessment in a patient with 4H leukodystrophy

Objective: POLR3-HLD or 4H leukodystrophy is an autosomal recessive disorder characterized by hypomyelination, hypodontia, and hypogonadotropic hypogonadism, and caused by variants in POLR3A, POLR3B, POLR1C, or POLR3K genes. Neurological and non-neurological clinical features and disease severity vary. While previous studies reference variable cognition, this is the first report of 4H detailing a comprehensive neuropsychological assessment. Method: The current study presents a 20-year-old, English-speaking, right-handed, non-Hispanic White female with 12 years of education with genetically confirmed 4H POLR3B-related leukodystrophy without hormonal replacement treatment. Results: At age 4, developmental delays, ataxia, hearing loss, and abnormal dentition were present. Imaging, endocrinology, and neurologic examinations revealed hypomyelination, reduced cerebellar volume, delayed bone age density, osteopenia, and evidence of adrenarche without signs of true puberty. Neuropsychological assessment at age 20 revealed global cognitive impairment with intellectual, attention, verbal memory retrieval, construction, executive (e.g. processing speed, sustained attention) and math computation deficits, along with behavioral dysregulation. Conclusion: We present the first detailed neuropsychological assessment of a patient with 4H leukodystrophy. The neuropsychological assessment revealed cognitive and behavioral dysexecutive deficits aligning with hypomyelination observed on imaging. Further longitudinal studies are needed to shed light on the neurobehavioral presentation associated with this disorder to assist care providers, patients, and their families.

Letrozole-stimulated endometrial preparation protocol is a superior alternative to hormone replacement treatment for frozen embryo transfer in women with polycystic ovary syndrome, a cohort study

BackgroundThe current routine endometrial preparation protocol for women with polycystic ovary syndrome (PCOS) is hormone replacement treatment (HRT). Letrozole is rarely used in frozen embryo cycles. Evidence confirming whether letrozole-stimulated (LS) protocol is suitable for frozen embryo transfer in patients with PCOS and for whom is suitable remains lacking.MethodsThis was a retrospective cohort study involving all frozen embryo transfer cycles with LS and HRT for PCOS during the period from Jan 2019 to December 2020 at a tertiary care center. Multivariate Logistic regression was used to analyze the differences in clinical pregnancy rate, live birth rate, miscarriage rate, the incidence of other pregnancy and obstetric outcomes between LS and HRT protocols after adjusting for possible confounding factors. Subgroup analysis was used to explore the population for which LS protocol was suitable.ResultsThe results of multivariate logistic regression showed that LS was significantly associated with a higher clinical pregnancy rate (70.9% vs. 64.4%;aOR:1.41, 95%CI: 1.18,1.68), live birth rate (60.5% vs. 51.4% aOR:1.49, 95%CI: 1.27,1.76), and a lower risk of miscarriage (14.7% vs. 20.1% aOR: 0.68, 95%CI: 0.53,0.89), hypertensive disorders of pregnancy (6.7% vs. 8.9% aOR: 0.63, 95%CI: 0.42,0.95), and gestational diabetes mellitus (16.7% vs. 20.7% aOR:0.71, 95%CI: 0.53,0.93) than HRT. There were no significant differences in other outcomes such as preterm birth, cesarean delivery, small for gestational age, or large for gestational age between the two endometrial preparation protocols. Subgroup analysis showed that LS had higher live birth rates than HRT in most of the subgroups; in the three subgroups of maternal age ≥ 35 years, menstrual cycle < 35 days, and no insulin resistance, the live birth rates of the two endometrial preparation protocols were comparable.ConclusionsLS protocol could improve the live birth rate and reduce the incidence of miscarriage, hypertensive disorders of pregnancy and gestational diabetes mellitus in patients with PCOS. LS protocol is suitable for all types of patients with PCOS. LS should be considered the preferred endometrial preparation protocol for women with PCOS.

Luteal phase support using micronized vaginal progesterone as pessaries or capsules in artificial cycles: is there any difference?

Research questionIs there a difference between the proportion of patients with serum progesterone <8.8 ng/ml on the day of embryo transfer when micronized vaginal progesterone (MVP) for luteal phase support (LPS) is given as pessaries versus capsules? DesignThis retrospective, matched-cohort, single-centre study compared pessaries (Cyclogest) versus capsules (Utrogestan, Progeffik) for LPS in hormone replacement treatment–embryo transfer (HRT-ET) cycles. Patients under 50 years old with a triple-layer endometrial thickness of ≥6.5 mm underwent transfer of one or two blastocysts. Serum progesterone concentrations were measured on the day of transfer; patients with concentrations <8.8 ng/ml received a single ‘rescue’ dose of additional progesterone by subcutaneous injection. ResultsIn total 2665 HRT-ET cycles were analysed; 663 (24.9%) used pessaries for LPS and 2002 (75.1%) used capsules. Mean serum progesterone concentrations with standard deviations on the day of embryo transfer were significantly higher in the group using MVP pessaries compared with those using capsules (14.5 ± 5.1 versus 13.0 ± 4.8 ng/ml; P = 0.000). The percentage of participants with suboptimal serum progesterone concentrations on the day of embryo transfer (<8.8 ng/ml) was significantly lower in the pessary group than the capsule group (10.3%, 95% confidence interval [CI] 7.9–12.6% versus 17.9%, 95% CI 16.2–19.6%; adjusted odds ratio 0.426, 95% CI 0.290–0.625; P = 0.000). No differences in pregnancy outcome were observed between the groups. ConclusionsUsing MVP pessaries rather than capsules for LPS resulted in significantly fewer patients having suboptimal serum progesterone concentrations on the day of embryo transfer. Consequently, almost 50% fewer patients in the pessary group needed rescue treatment.

SAT609 Panhypopituitarism Secondary To Pituitary Abscess In A Patient With Neurobrucellosis

Abstract Disclosure: G. De la Peña Sosa: None. A. Cabello Hernández: None. M. Gómez Sámano: None. F. Gómez Pérez: None. Background: Pituitary abscess is a rare but potentially life-threatening disease that could lead to panhypopituitarism. It is important to suspect the diagnosis, especially in regions of the world with endemic infectious diseases. Clinical Case: A 55-year, farmer, with a history of consumption of unpasteurized dairy products, began in February 2023 with headache, impaired consciousness and fever. Initial tests were consistent with neuroinfection: lumbar puncture with cerebrospinal fluid (CSF) with elevated proteins (&amp;gt;200 mg/dL, n &amp;lt;45 mg/dL), decreased glucose (14 mg/dL with a serum glucose of 76 mg/dl), pleocytosis (800 mm3, n &amp;lt;5 mm3). Head CT-scan did not report alterations. Antibiotic treatment was started due to diagnosis of acute meningitis. Later Brain MRI was performed showing ventriculitis; the pituitary gland was heterogeneous with the presence of an 8x8mm abscess.Pituitary axis hormones were evaluated, showing results compatible with panhypopituitarism with central hypothyroidism (normal serum TSH 1.05 mIU/L (n 0.3-5 mIU/L), decreased free T4 0.57 ng/dL (n 0.63-1.34 nd/dL), decreased total T3 0.47 ng/mL (n 0.64-1.81 ng/mL)), central hypocortisolism (decreased morning cortisol levels 5.72 mcg/dL (n 6.7-22.6 mcg/dL) and ACTH 20 pg/mL (n 10-50 pg/ml)), central hypogonadism (decreased LH &amp;lt;0.20 mUI/mL (n 1.24-862 mUI/mL), decreased FSH 0.37 mUI/mL (n 1.27-19.26 mUI/mL), decreased testosterone 0.24 ng/mL (n 1.75-7.81 ng/mL)), growth hormone deficiency (decreased IGF-1 9.99 ng/mL (n 61-206 ng/mL)). Hormone replacement treatment with hydrocortisone and levothyroxine was started. Due to the epidemiological background, Rose Bengal test for Brucella spp. was performed, with positive results (n negative) and 2-mercaptoethanol Brucella agglutination test was also positive &amp;gt;1:20 (n &amp;lt;1:20). Diagnosis of neurobrucellosis was made and treatment with doxycycline, rifampin and ceftriaxone was started. Neurosurgery service suggested conservative management with antibiotics. Patient showed improvement in his neurological status and infectious symptoms disappeared. Subsequent pituitary MRI showed pituitary intraglandular abscess with a 15% decrease.The patient was discharged six weeks later with prednisone, levothyroxine, somatropin and testosterone, as well as doxycycline and rifampin for another 4 months. Conclusion: Pituitary abscess should be considered in a differential diagnosis of patients with neuro infection symptoms, panhypopituitarism and heterogenous image in the MRI. Opportune medical management may result in a lower mortality and a higher recovery of pituitary hormone function. Reference: Karagiannis, Apostolos K A et al. “Pituitary abscess: a case report and review of the literature.” Endocrinology, diabetes &amp; metabolism case reports vol. 2016 (2016): 160014. doi:10.1530/EDM-16-0014 Presentation: Saturday, June 17, 2023

FRI524 Improving The Quality Of Life In Patients With Not Adequately Treated Hypothyroidism: The Impact Of Comprehensive Thyroid Care For Hypothyroid Patients

Abstract Disclosure: V. Högqvist Tabor: Consulting Fee; Self; Butterfly Technologies Inc. M. Tarasova: Employee; Self; Butterfly Technologies Inc. Owner/Co-Owner; Self; Butterfly Technologies Inc. G. Cohen-Skalli: Owner/Co-Owner; Self; Butterfly Technologies Inc. F. Dubois: Employee; Self; Butterfly Technologies Inc. B. Curran: Employee; Self; Butterfly Technologies Inc. Underactive thyroid is affecting approximately 25 million people in the USA. Even though the treatment of the basic condition has been established in form of hormone replacement, there is a considerably large group of patients that continues to experience a plethora of hypothyroidism symptoms and suffer from poor quality of life. The lack of individualized approach, combined with the lack of preventive health management strategies, increases the risk of many health complications: obesity, type 2 diabetes, depressive spectrum disorders, infertility, muscle and bone problems, heart conditions, and dementias. Presently, the Paloma Health Thyroid Solution consists of a virtual clinic providing holistic thyroid care and an app for hypothyroid patients, it enables patients to receive care by medical experts in the field of endocrinology, autoimmune diseases and hypothyroidism as well as a nutritionist. In addition, it provides at-home thyroid hormone test kits, symptom recording, offers a library of informational articles, and connects the community of hypothyroid patients. The 12-week program offered to new patients facilitates learning about the most important aspects of managing the condition, including implementation of a phased elimination diet (known as the Autoimmune Protocol, AIP). Patients reported to feel more empowered, taken care of and understood after using Paloma Health Thyroid Solution. At the same time physicians have a real-time patient dashboard, and can promptly recognise signs of health worsening in patients and help correct the health management. In order to evaluate the usefulness of the approach, we have selected 45 patients that were diagnosed with hypothyroidism for at least six months, have been prescribed hormone replacement treatment, and have reported (i) low energy, (ii) low focus, (iii) sensitivity to cold, and (iv) headaches. Symptoms were recorded on a 5-point Likert scale starting from the most intense symptom experience to the absence of the symptom. We analyzed recorded symptoms, starting at the first day when patients started using Paloma Health Thyroid Solution and for the next 12 weeks. We averaged symptom experiences per patient, per week in order to have a better representation of symptom intensity for each given week. We found that patients using Paloma Health comprehensive services significantly improved symptoms related to an under-active thyroid: energy, focus, intolerance to cold and headache. The improvement was first detectable after 2 weeks of start of Paloma Health Thyroid Service, and continued the positive improvement trend for the full duration of the time period. Here we show for the first time that using the combination of accessible and individualised approach, coupled with digital technology enabling easy access to both skilled healthcare specialists as well as the vetted information and empathic support services (care manager and community) can help patients experiencing unresolved thyroid symptoms, despite previously prescribed therapy. Using virtual clinics offering preventive health management catered specifically to each individual holds a promise of helping the group of patients that currently do not fully benefit from one approach-fits-all treatment that has been hampering hypothyroid health management for the past 40 years. This approach has the potential to both reduce the burden on patients and healthcare practitioners and save costs for payers. Presentation: Friday, June 16, 2023

Pretreatment with a long-acting GnRH agonist for frozen-thawed embryo transfer cycles: how to improve live birth?

BackgroundWhether pretreatment with gonadotropin-releasing hormone agonist (GnRHa) can improve the pregnancy outcomes in frozen-thawed embryo transfer (FET) cycles is controversial. The inconsistencies in the results of different studies would be related to the characteristics of the included patients and the protocol of GnRHa use. In this study, we investigated the efficacy of pretreatment with a long-acting GnRH agonist in the early follicular phase of FET cycles and determined which population was suitable for the protocol.ResultsWe retrospectively included 630 and 1141 patients in the GnRHa FET and hormone replacement treatment (HRT) FET without GnRHa groups respectively, between October 2017 and March 2019 at a university-affiliated in vitro fertilization center. On the second or third day of menstruation, 3.75 mg of leuprorelin was administered. After 14 days, HRT was initiated for endometrial preparation. No significant differences were observed between the two groups in terms of patient characteristics. However, the GnRHa FET group showed a higher percentage of endometrium with a triple line pattern (94.8% vs 89.6%, p < 0.001) on the day of progesterone administration, with increased implantation (35.6% vs 29.8%, p = 0.005), clinical pregnancy (49.8% vs 43.3%, p = 0.008), and live birth rate (39.4% vs 33.7%, p = 0.016), than the HRT FET cycles with similar endometrial thickness, ectopic pregnancy and early miscarriage rates. Binary logistic regression analysis showed the GnRHa FET group to be associated with an increased chance of clinical pregnancy (P=0.028, odds ratio [OR] 1.32, 95% confidence interval [CI] 1.03–1.70) and live birth (P=0.013, odds ratio [OR] 1.34, 95% confidence interval [CI] 1.06–1.70) compared to the HRT FET without GnRHa group. After subgroup analysis, we found that the GnRHa FET group showed a significantly higher live birth rate in the subgroups of age < 40 years, primary infertility, with polycystic ovary syndrome (PCOS), and irregular menstruation.ConclusionsPretreatment with a long-acting GnRHa during the early follicular phase improved the live birth rate in FET cycles. Age < 40 years, primary infertility, PCOS, and irregular menstruation are effective indications for endometrial preparation with GnRHa pretreatment in FET cycles. However, further randomized controlled trials are required to verify these results.

Effect of thyroid hormone replacement treatment on cardiac diastolic function in adult patients with subclinical hypothyroidism: a meta-analysis.

Although subclinical hypothyroidism (SCH) is related to abnormalities in left ventricular diastolic function, the use of levothyroxine as a regular treatment remains debatable. This meta-analysis aimed to determine whether thyroid hormone replacement therapy affects cardiac diastolic function in patients with SCH as measured by echocardiography. This meta-analysis included a search of the EMBASE, PubMed, Web of Science, and Cochrane Library databases from their inception to May 18, 2023, for studies analyzing cardiac morphology and functional changes in patients with SCH before and after thyroid hormone replacement. The outcome measures were cardiac morphology and diastolic and overall cardiac function, as assessed using ultrasound parameters (including ventricular wall thickness, chamber size, mitral wave flow, tissue Doppler, and speckle tracking). The quality of the studies was assessed using the Newcastle-Ottawa Scale. The standard mean differences (MDs) and 95% confidence intervals (CI) were calculated using fixed- or random-effects models. Seventeen studies met the inclusion criteria. A total of 568 patients participated and completed the follow-up. All studies specifically stated that serum thyrotropin levels returned to normal by the end of the study period. Compared with baseline levels, no significant morphological changes were observed in the heart. In terms of diastolic function, we discovered that the ratios of E-velocity to A-velocity (E/A) had greatly improved after thyroid hormone replacement therapy, whereas the ratios of the mitral inflow E wave to the tissue Doppler e' wave (E/e') had not. Global longitudinal strain (GLS) increased significantly after treatment with levothyroxine. In adult patients with SCH, thyroid hormone supplementation can partially but not completely improve parameters of diastolic function during the observation period. This meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 statement, an updated guideline for reporting systematic reviews (11) and was registered with INPLASY (INPLASY202320083). https://inplasy.com/inplasy-2023-2-0083.

Young women were associated with higher risk of hypertensive disorders of pregnancy and cesarean section from hormone replaced cycles in frozen-thawed embryo transfer: a retrospective study of 5316 singleton deliveries.

The utilization of frozen-thawed embryo transfer (FET) cycles has been linked to heightened risks of adverse perinatal outcomes. However, the potential association between adverse perinatal outcomes and distinct endometrial preparation regimens remains unclear. Therefore, we aim to investigate the maternal and neonatal outcomes after hormone replacement treatment (HRT) cycles, natural cycles (NC) and HRT cycles with pretreatment using GnRHa (HRT + GnRHa) for ovulatory women undergoing FET cycles. A large sample retrospective cohort study was carried out from 2016 to 2020. The data included a total of 5316 women who had singleton deliveries undergoing FET cycles and which were divided into three groups based on different endometrial preparation protocols: 4399 patients in HRT groups, 621 in GnRHa+HRT groups, 296 in NC groups. The outcomes consisted of maternal outcomes (cesarean section, hypertensive disorders of pregnancy (HDP), placenta previa, gestational diabetes mellitus (GDM));and neonatal outcomes (preterm birth, newborn birthweight, low birthweight, small for gestational age (SGA), macrosomia, large for gestational age (LGA), fetal malformation). After adjusting for a series of confounding variables, we found an increased risk of HDP (aOR=3.362; 95%CI, 1.059-10.675) and cesarean section (aOR=1.838; 95%CI, 1.333-2.535) in HRT cycles compared with NC, especially for ovulatory women under 35 years old. However, in all three groups, newborn birth weight was not significantly different. Meanwhile, perinatal outcomes did not differ significantly in terms of perinatal outcomes in HRT +GnRHa cycles compared with HRT cycles solely. During FET cycles, singletons from HRT were related to higher risks of HDP and cesarean section, particularly for young women. GnRHa pretreatment didn't bring any benefit to perinatal outcomes compared with HRT cycles alone. Therefore, the natural cycle may be a more appropriate and safer option for young ovulatory women.

Finding of the optimal preparation and timing of endometrium in frozen-thawed embryo transfer: a literature review of clinical evidence.

Frozen-thawed embryo transfer (FET) has been a viable alternative to fresh embryo transfer in recent years because of the improvement in vitrification methods. Laboratory-based studies indicate that complex molecular and morphological changes in endometrium during the window of implantation after exogenous hormones with controlled ovarian stimulation may alter the interaction between the embryo and endometrium, leading to a decreased implantation potential. Based on the results obtained from randomized controlled studies, increased pregnancy rates and better perinatal outcomes have been reported following FET. Compared to fresh embryo transfer, fewer preterm deliveries, and reduced incidence of ovarian hyperstimulation syndrome were found after FETs, yet there is a trend of increased pregnancy-related hypertensive diseases in women receiving FET. Despite the increased application of FET, the search for the most optimal priming protocol for the endometrium is still undergoing. Three available FET protocols have been proposed to prepare the endometrium: i) natural cycle (true natural cycle and modified natural cycle) ii) artificial cycle (AC) or hormone replacement treatment cycle iii) mild ovarian stimulation (mild-OS) cycle. Emerging evidence suggests that the optimal timing for FET using warmed blastocyst transfer is the LH surge+6 day, hCG administration+7 day, and the progesterone administration+6 day in the true natural cycle, modified natural cycle, and AC protocol, respectively. Although still controversial, better clinical pregnancy rates and live birth rates have been reported using the natural cycle (true natural cycle/modified natural cycle) compared with the AC protocol. Additionally, a higher early pregnancy loss rate and an increased incidence of gestational hypertension have been found in FETs using the AC protocol because of the lack of a corpus luteum. Although the common clinical practice is to employ luteal phase support (LPS) in natural cycles and mild-OS cycles for FET, the requirement for LPS in these protocols remains equivocal. Recent findings obtained from RCTs do not support the routine application of endometrial receptivity testing to optimize the timing of FET. More RCTs with rigorous methodology are needed to compare different protocols to prime the endometrium for FET, focusing not only on live birth rate, but also on maternal, obstetrical, and neonatal outcomes.

Live birth after letrozole-stimulated cycles versus hormone replacement treatment cycles for the first frozen embryo transfer in women with polycystic ovary syndrome: protocol for a multicentre randomised controlled trial

IntroductionHormone replacement treatment (HRT) is the most commonly used endometrial preparation protocol for frozen embryo transfer (FET) in patients with polycystic ovary syndrome (PCOS). However, studies have found that HRT...

P-490 Impact of follicular phase characteristics on mid-luteal progesterone and ongoing pregnancy rates: Lessons learned from true natural cycle frozen embryo transfer

Abstract Study question Is there an association between follicular phase endocrine and ultrasonographic characteristics and ongoing pregnancy rates (OPRs) in true-natural cycle (t-NC) frozen embryo transfers (FETs)? Summary answer Endometrial thickness one day before ovulation is the only independent predictor of ongoing pregnancy (OP) in t-NC FET cycles. What is known already In ovulatory women, NC FET is currently being proposed instead of the hormonal replacement treatment (HRT) protocol since HRT is associated with increased maternal and obstetric risk factors, most probably due to the absence of a corpus luteum. However, the presence of ovulation in regularly cycling women does not guarantee a receptive endometrium. Currently, there is a lack of data regarding the impact of follicular phase endocrine and ultrasonographic parameters on mid-luteal progesterone (P4) levels and OPRs in t-NC FET cycles. Study design, size, duration A cohort study of 229 women who underwent warmed blastocyst transfer employing t-NC. Three strategies were adopted. During January 2017-June 2017, serum P4 was not monitored. During July 2017-June 2020, serum P4 was routinely monitored on the FET-1 day. During July 2020-August 2022, a rescue strategy with daily 25-mg subcutaneous progesterone was adopted for patients with P4 levels between 7-10 ng/mL. In patients with serum P4&amp;lt;7 ng/mL FET was cancelled. Participants/materials, setting, methods Staying in-town and having regular menstrual cycles, permitting intensive endocrine and ultrasonographic monitoring (daily serum estradiol [E2], luteinizing hormone [LH], P4, and transvaginal ultrasonography), starting mid-cycle until confirmation of ovulation was the only inclusion criteria. Only the first FET cycle per patient was included. The primary outcome measure was OPR. The impact of follicular phase endocrine and ultrasonographic parameters on serum P4 levels on the FET-1 day and OPRs were evaluated using regression analysis. Main results and the role of chance Follicular phase parameters, including follicular phase length, late follicular phase E2, LH, P4 levels, and maximal follicle diameter before ovulation, were not significant predictors of ongoing pregnancy (OP) in t-NC FET. In contrast, the endometrial thickness one day prior to ovulation was a significant independent predictor of OP (adjusted OR = 1.29, 95% CI:1.06-1.56). When endometrial thickness before ovulation was assessed in quartiles, univariate OPRs in the 25th (&amp;lt;9.1 mm), 25-50th (9.1-10.1mm), 51-75th (10.2-11.6 mm) and &amp;gt;75th (&amp;gt;11.6 mm) percentiles were 43.3%, 47.3%, 71.7%, and 54.7%, respectively (p=0.016). Following logistic regression analysis, the adjusted ORs for OPR of the 51-75th (3.69, 95% CI:1.42-9.56) and &amp;gt;75th (2.86, 95% CI: 1.06-7.73) percentiles were significantly higher when compared with that of &amp;lt; 25th. The three strategies for monitoring/acting (rescue if needed) based on serum P4 levels on the FET-1 day were associated with similar adjusted ORs for OP. Notably, cancellation of cycles with serum P4 &amp;lt;7 ng/mL and adopting a rescue policy for those with 7-10 ng/mL did not increase OPRs. After multivariate linear regression analysis, late follicular E2 levels (ß-coefficient: 0.399 ng/mL, 95% CI:0.007;0.021) and BMI (ß-coefficient: −0.292 ng/mL, 95% CI: −0.730;-0.222) were the only significant predictors of P4 levels on the FET-1 day. Limitations, reasons for caution Limitations include the cohort study design evaluating three different policies, the single point serum P4 assessment, and adopting an arbitrary lower cut-off of &amp;lt; 7 ng/mL for cycle cancellation and 7-10 ng/mL for a rescue strategy. Wider implications of the findings Endometrial thickness one day before ovulation was the only significant predictor of OP in t-NC FET cycles. Apart from endometrial thickness, none of the follicular phase parameters were significant predictors of OP. Single-point assessment of serum P4 may not be reliable when assessing reproductive outcomes in t-NC FET. Trial registration number Not applicable

P-519 Is oral dydrogesterone a good alternative to vaginal micronized progesterone for luteal phase support in women receiving oocyte donation?

Abstract Study question Does oral dydrogesterone (OD) in luteal phase support (LPS) provide equivalent clinical pregnancy and miscarriage rates as micronized vaginal progesterone (MVP) in oocyte donation recipients? Summary answer No significant difference in clinical pregnancy and miscarriage rates was observed when using OD instead of MVP for LPS in oocyte donation. What is known already Dydrogesterone has a higher bioavailability than MVP due to its high specificity for progesterone receptors allowing the use of lower doses limiting side effects. In addition, because of its route of administration, its tolerance is better. The use of OD for LPS in fresh IVF cycles is now well recognized. However, few data are available on its use in frozen-thawed embryo transfer especially in artificial cycles. In this situation, the lack of corpus luteum leads to a total dependence on exogenous progestogens for implantation and maintenance of the pregnancy. Study design, size, duration A retrospective observational study was performed from prospectively collected data in the ART Department of Lille University Hospital from July 2018 to July 2022. Participants/materials, setting, methods Our study analysed 372 oocyte donation cycles with embryo transfer. Recipients underwent endometrial preparation by hormone replacement treatment (artificial cycles). LPS was provided by weekly intramuscular progesterone (500 mg/2ml) and either OD 40 mg per day or MVP 800 mg per day for 12 weeks if the pregnancy test was positive. The primary endpoint was clinical pregnancy rate. Main results and the role of chance This study compared the outcome of 162 transfers with dydrogesterone + IM progesterone to the outcome of 210 transfers with the MVP + IM progesterone. No significant difference was found between the two groups except for the number of embryos transferred, embryo quality, donor BMI and fresh or frozen status of the embryo. After adjustment for these criteria, our two groups were comparable in clinical pregnancy rates with 36.67% in the MVP group versus 30.25% in the OD group (OR 0.868 [0.529 ; 1.423], p = 0.57), ongoing pregnancy rates (29.05% versus 25.31%, OR 0.993 [0.591; 1.669], p = 0.97), miscarriage rates (7.62% versus 4.94%, OR 0.640 [0.248; 1.650], p = 0.35) and live birth rates (26.67% versus 17.69%, OR 0.727 [0.412; 1.284], p = 0.27). Limitations, reasons for caution The main limitation of this study is the non-randomisation of data between the two treatment groups. Wider implications of the findings Our study suggests that dydrogesterone has a place in our LPS strategies in artificial cycle for frozen embryo transfers or in oocyte donation, especially as this route is often preferred by patients and very well tolerated. Further prospective cohorts or randomized trials could continue to inform clinical practice on LPS. Trial registration number DEC 16-25

P-612 Comparison the effectiveness and safety of letrozole-stimulated and hormone replacement treatment in endometrial preparation for frozen embryo transfer in patients with polycystic ovary syndrome

Abstract Study question Whether letrozole-stimulated protocol has advantages over hormone replacement therapy (HRT) in frozen embryo transfer in patients with polycystic ovary syndrome (PCOS)? Summary answer Letrozole-stimulated protocol is more suitable for endometrial preparation than HRT in patients with PCOS, which can increase the live birth rate and reduce pregnancy complications. What is known already The current routine endometrial preparation protocol for women with PCOS is HRT. However, HRT is expensive, and recent studies have found HRT may increase the risk of adverse maternal and neonatal complications such as hypertensive disorders of pregnancy. Letrozole induces mono-ovulatory and has no antiestrogenic effect, and has been found to increase live birth rate compared with clomiphene in fresh embryo cycles. However, Letrozole is rarely used in frozen embryo cycles. Whether letrozole-stimulated protocol is suitable for frozen embryo transfer in patients with PCOS and for whom is suitable is still lack of evidence. Study design, size, duration This is a retrospective cohort study involving all frozen embryo transfer cycles with letrozole-stimulated and HRT for PCOS during the period from August 2018 to December 2020 at a tertiary care center. Participants/materials, setting, methods A total of 2011 letrozole-stimulated cycles and 2211 HRT cycles were included in the analysis. Multivariate Logistic regression was used to analyze the differences in clinical pregnancy rate, live birth rate, miscarriage rate, the incidence of other pregnancy and obstetric outcomes between letrozole-stimulated protocol and HRT after adjusting for possible confounding factors. Subgroup analysis was used to explore the population for which letrozole-stimulated protocol was suitable. Main results and the role of chance After adjusting for confounding, letrozole-stimulated protocol increased the clinical pregnancy rate (OR,1.44; 95%CI,1.21-1.70), live birth rate (OR,1.49; 95%CI,1.27-1.74) and reduced the incidence of miscarriage (OR, 0.71; 95%CI,0.55-0.92), hypertensive disorders of pregnancy (OR, 0.66; 95%CI,0.45,0.98), gestational diabetes mellitus (OR,0.75; 95%CI,0.57,0.98) and cesarean section (OR,0.78; 95%CI,0.61,0.99) than HRT. There were no significant differences in other outcomes such as preterm birth, small for gestational age, and large for gestational age between the two endometrial preparation protocols. Subgroup analysis according to maternal age, BMI, insulin resistance and PCOS classification showed that the live birth rate of letrozole-stimulated protocol was significantly higher than that of HRT in all subgroups. Limitations, reasons for caution This study is a retrospective study, the population characteristics of the two endometrial preparation protocols existed differences. Although multivariate logistic regression was used to adjust some factors, the interference of known and unknown factors on the outcomes cannot be completely avoided. Wider implications of the findings This retrospective study found letrozole-stimulated protocol has more advantages than HRT, which can improve the live birth rate and reduce the incidence of hypertensive disorders of pregnancy, gestational diabetes mellitus in patients with PCOS. High-quality well-powered randomised clinical trials and possible mechanistic studies are needed to further validate this conclusion. Trial registration number NA