Hormone Replacement Treatment Research Articles

Comparison of pregnancy outcomes in women undergoing frozen thawed embryo transfer (FET) cycles following ultrasound for endometrial morphology with and without Doppler studies- a prospective cohort study

Introduction: There is a paucity of data evaluating role of endometrial blood flow in frozen thawed embryo transfer cycles (FET cycles) in hormone replacement treatment (HRT) cycles. Objective: To compare pregnancy outcomes in women undergoing ultrasound for endometrial morphology alone to those with endometrial morphology with blood flows in frozen embryo transfer cycles. Patients: Patients aged 23 to 38 years undergoing first two frozen thawed single blastocyst embryo transfer cycles. From August 2019 to January 2020, 163 patients undergoing hormone replacement frozen embryo transfer cycles were enrolled in the study. Patients were divided in two groups. Patients in group A (n = 92) had ultrasonographic evaluation of endometrial thickness and morphology and in group B (n = 71) patients underwent ultrasound for endometrial thickness, morphology along with Doppler blood flow studies. Outcome measures: Primary outcome was clinical pregnancy rate. Secondary outcome measures were pregnancy loss rate, ongoing pregnancy rate, and ectopic pregnancy rate. Results: Clinical pregnancy rate in group A and group B was 54.34% and 47.88%. Clinical pregnancy rate was similar between both the groups (P = 0.779). Ongoing pregnancy rate in group A and B was 48.91% and 40.84%, respectively. Pregnancy loss rate (7–13 wks) was 5.4% and 7.04% in group A and group B, respectively. There was no significant difference in ongoing pregnancy rate and pregnancy loss rate between both the groups (P = 0.756). Conclusion: Additional measurement of doppler studies do not help in improving implantation and thus seems unnecessary in improving pregnancy rates and reducing pregnancy loss rates in FET cycles.

Progestérone et transfert d’embryon congelé préparé par traitement hormonal substitutif : état des lieux des pratiques

Frozen-thawed embryo transfer (FET) has recently become the most frequently performed ART procedure. Many protocols for endometrial preparation are used, without any evidence-based superiority of one protocol above the others. Most French fertility centers mainly use hormonal replacement treatment (HRT) for endometrial preparation for organizational reasons. According to some studies, early pregnancy losses rate is higher with HRT endometrial preparation for FET than with other protocols, leading to new insights in improving outcomes into ART centers. There is a lack of consensual guidelines regarding the use of HRT for FET: there are various protocols, with different dosages, duration and routes for progesterone (PG) prescription. To date, the vaginal route is the most popular around the world as it gives higher intra-uterine concentration of PG because of the first uterine pass. However, recent scientific publications have pointed the importance of PG measurement in order to detect a lack of PG supplementation. Whatever the route of administration, it seems that a significant proportion of patients do not reach adequate PG concentrations for successful implantation and ongoing pregnancy. Timing of the measurement and ideal serum PG rate to reach are yet to be defined. What treatment strategy to adopt according to the results is still under investigation. Individualization of PG doses and routes of administration could lead to a decrease in miscarriages and better outcome.

Therapeutic Anabolic and Anticatabolic Benefits of Natural Chinese Medicines for the Treatment of Osteoporosis.

Osteoporosis is a bone disease characterized by increasing osseous fragility and fracture due to the reduced bone mass and microstructural degradation. Primary pharmacological strategies for the treatment of osteoporosis, hormone replacement treatment (HRT), and alendronate therapies may produce adverse side-effects and may not be recommended for long-term usage. Some classic and bone-specific natural Chinese medicine are very popularly used to treat osteoporosis and bone fracture effectively in clinical with their potential value in bone growth and development, but with few adverse side-effects. Current evidence suggests that the treatments appear to improve bone metabolism and attenuate the osteoporotic imbalance between bone formation and bone resorption at a cellular level by promoting osteoblast activity and inhibiting the effects of osteoclasts. The valuable therapies might, therefore, provide an effective and safer alternative to primary pharmacological strategies. Therefore, the purpose of this article is to comprehensively review these classic and bone-specific drugs in natural Chinese medicines for the treatment of osteoporosis that had been deeply and definitely studied and reported with both bone formation and antiresorption effects, including Gynochthodes officinalis (F.C.How) Razafim. & B.Bremer (syn. Morinda officinalis F.C.How), Curculigo orchioides Gaertn., Psoralea corylifolia (L.) Medik Eucommia ulmoides Oliv., Dipsacus inermis Wall. (syn. Dipsacus asperoides C.Y.Cheng & T.M.Ai), Cibotium barometz (L.) J. Sm., Velvet Antler, Cistanche deserticola Ma, Cuscuta chinensis Lam., Cnidium monnieri (L.) Cusson, Epimedium brevicornum Maxim, Pueraria montana (Lour.) Merr. and Salvia miltiorrhiza Bunge., thus providing evidence for the potential use of alternative Chinese medicine therapies to effectively treat osteoporosis.

Effect of endometrial thickness on ectopic pregnancy in frozen embryo transfer cycles: an analysis including 17,244 pregnancy cycles

To investigate whether endometrial thickness (EMT) influences the incidence of ectopic pregnancy (EP) in frozen embryo transfer (FET) cycles. Retrospective cohort study. Academic tertiary-care medical center. A total of 16,556 patients were enrolled between January 2010 and December 2017, comprising 16,701 intrauterine, 488 ectopic, and 45 heterotopic pregnancy cycles after FET. None. EP was the primary outcome. EMT was the main measured variable. Data were analyzed with the binary logistic general estimating equations model to calculate the adjusted odds ratio (aOR) for EP. After adjusting for confounders, EMT remained statistically significant as an independent risk factor for EP. Compared with women with an EMT of ≥14 mm, the aORs for women with EMT in the ranges 7-7.9, 8-9.9, and 10-11.9 mm were 2.70 (95% confidence interval [CI], 1.65-4.40), 2.06 (95% CI, 1.33-3.20), and 1.66 (95% CI, 1.07-2.58), respectively. Hormone replacement treatment for endometrial preparation during FET increased the risk of EP after adjustment for confounding variables. EMT is inversely proportional to EP rate in FET cycles and is therefore a potential quantitative marker of endometrial receptivity and uterine contractibility in an FET cycle. The predictive validity of EMT value must be evaluated in further studies.

Combined effects of growth hormone and testosterone replacement treatment in heart failure.

AimsAlthough preliminary studies have demonstrated safety and effectiveness of single replacement therapy for growth hormone deficiency or testosterone deficiency in heart failure (HF), no data are available regarding the combined treatment with both GH and T in this setting. Thus, the aim of the present hypothesis generating pilot study was to evaluate the effectiveness and safety of multiple hormonal replacement therapies in chronic HF.Methods and resultsFive stable HF with reduced ejection fraction patients, with a concomitant diagnosis of growth hormone deficiency and testosterone deficiency, on top of guideline‐based HF treatment underwent 1 year of GH replacement therapy by subcutaneous injections of somatotropin at a dose of 0.012 mg/kg every second day. After 12 months, a T replacement treatment was added at a dosage of 1000 mg every 3 months. Each patient underwent a complete M‐mode, two‐dimensional, and Doppler echocardiographic examination, and an incremental symptom‐limited cardiopulmonary exercise test on a bicycle ergometer at baseline (BL), after 1 year of GH treatment (V1), and after 1 year of combined GH + T treatments (V2). One‐year of GH treatment resulted in a significant improvement in left ventricular ejection fraction (+5.4%, P < 0.01), New York Heart Association functional class (P < 0.05), and peak oxygen consumption (VO2 peak) (+19.3%, P < 0.01), and in a significant reduction in NT‐proBNP levels (−35.1%, P < 0.01). Notably, one additional year of combined GH and T replacement therapy induced a further increase in VO2 peak (+27.7%, final delta change + 52.44%, P < 0.01), as well as a significant improvement in muscular strength, as assessed by handgrip dynamometry (+17.5%, final delta change + 25.8%, P < 0.01). These beneficial effects were paralleled with an improvement of the overall clinical status (as assessed by New York Heart Association class). Of note, neither adverse effects nor cardiovascular events were reported during the follow‐up period.ConclusionsOur preliminary data suggest for the first time that combined replacement therapy with GH and T could be considered safe and therapeutic in HF patients with multiple hormone deficiencies, supporting the hypothesis that multiple hormone deficiencies syndrome can be considered as a novel and promising therapeutic target in HF. Further studies with a more robust design and larger population are needed.

Relationship between serum progesterone concentrations and pregnancy rates in hormone replacement treatment-frozen embryo transfer using progesterone vaginal tablets

In assisted reproductive technology (ART), hormone replacement treatment embryo transfer (HRT-ET) is common. However, the appropriate serum progesterone concentration is not well known in the case of transvaginal progesterone administration. The purpose of the current study is to investigate the relationship between serum progesterone concentration and pregnancy rate in HRT-ET using progesterone vaginal tablets. This is a retrospective cohort study, the authors investigated all patients who underwent HRT-ET at this hospital for the first time from September 1, 2010 to September 30, 2015. A total of 227 cycles were performed in all 123 patients who underwent HRT-ET. In the total 123 cycles of first time HRT-ET, 32 cycles (26.0%) developed a pregnancy. The results of the multivariate analysis indicated that the patient’s age, embryo grade, serum estradiol concentration, and progesterone concentration had significant differences in relation to the pregnancy rate (p &lt; 0.05). The latter rate tends to be lower when the serum progesterone concentration is less than 5 or more than 15 ng/ml. Therefore, the authors suggest that the appropriate serum progesterone concentration ranges from 5 to 15 ng/ml in HRT-ET using progesterone vaginal tablets.

Diabetes in Menopause: Risks and Management.

The aim of this review is to present, critically appraise and qualitatively synthesize current evidence on the risk of type 2 diabetes mellitus (T2DM) development during menopause, the management of climacteric symptoms in women with T2DM and the management of T2DM in postmenopausal women. Menopause represents the end of reproductive life in women, as a result of ovarian aging. It is characterized by substantial decrease in the endogenous oestrogen concentrations and it is accompanied by alterations in body weight, adipose tissue distribution and energy expenditure, as well as insulin secretion, insulin sensitivity and activity that can predispose to the development of T2DM, independently of, and additively to, aging. Many women in midlife experience climacteric symptoms, including hot flushes and night sweats, resulting in an indication to receive Hormone Replacement Treatment (HRT). HRT has a favourable effect on glucose homeostasis both in women without and with T2DM. The latter was considered in the past as a cardiovascular disease (CVD) equivalent, which would suggest that women with the disease should not receive HRT. However, nowadays evidence exists to support an individualized approach of women based on their CVD risk, as some women with T2DM may be excellent candidates for HRT. Regarding T2DM management for women in menopause, lifestyle intervention, including diet and exercise, constitutes its cornerstone. However, most of these women will eventually require pharmacologic therapy. The most suitable agents should be selected according to their metabolic, cardiovascular and bone effects, taking into consideration the specific characteristics and comorbidities of each postmenopausal woman.

The Impact of Hormonal Replacement Treatment in Postmenopausal Women with Uterine Fibroids: A State-of-the-Art Review of the Literature.

Background and Objectives: Hormonal replacement therapy (HRT) is effective in treating many debilitating symptoms of menopause. However, its use in women with uterine fibroids is widely debated, based on the susceptibility of these tumors to sexual steroids. This review aims to ascertain the effects of HRT on leiomyomas development and growth in postmenopausal women. Materials and Methods: Electronic databases (i.e., MEDLINE, Scopus, ClinicalTrials.gov, EMBASE, Sciencedirect, the Cochrane Library at the CENTRAL Register of Controlled Trials, Scielo) were searched from January 1990 until May 2019. All English-written studies evaluating the impact of various HRT regimens on uterine leiomyomas were selected. Results: Seventeen papers, considering a total of 1122 participants, were included. Fifteen of these were prospective trials, of which nine were randomized controlled trials. The remaining two works were a retrospective observational trial and a retrospective case series respectively. Five studies evaluated the effects of tibolone, also comparing it with various estrogen/progestin combinations, while two were about raloxifene. Thirteen studies compared different combinations of estrogens/progestins, the most common being transdermal estrogens (used in nine studies) and medroxyprogesterone acetate at different doses (used in 10 studies). Conclusions: For women with uterine fibroids, the choice of the most appropriate HRT regimen is crucial to avoid leiomyomas growth and the symptoms possibly related to it. Available data are conflicting, but suggest that uterine fibroids might be influenced by HRT, without representing an absolute contraindication to hormonal replacement therapy. Women with uterine fibroids subjected to HRT should be periodically examined and hormonal treatment should be discontinued if leiomyomas appear to increase in size. Moreover, the minimal effective dose of progestin should be employed.

8. COMPARISON OF NATURAL CYCLES VERSUS HORMONE REPLACEMENT TREATMENT FOR 2398 FROZEN–THAWED EMBRYO TRANSFER CYCLES FOR PREIMPLANTATION GENETIC TESTING PATIENTS

Introduction Multiple studies have been performed to evaluate the efficiencies of various endometrial preparation protocols. However, to date, the most appropriate method of endometrial preparation for frozen-thawed embryo transfer (FET) remains debated. To our knowledge, there are no studies comparing FET cycle endometrial preparation protocol for PGT patients, and this study is the first study to compare FET cycle endometrial preparation protocols for PGT patients. Material & methods This retrospective analysis included 2398 FET cycles for 1497 preimplantation genetic testing (PGT) patients with regular menstrual cycles who underwent frozen-thawed single blastocyst transfer from January 2014 to December 2017. The patients were divided into two groups according to the method of endometrial preparation for FET: 586 cycles were natural cycles(NC), and 1812 cycles were hormone replacement treatment (HRT). Reproduction-related clinical outcomes of the two groups were compared. Results The NC group showed a higher clinical pregnancy rate (54.78% vs 51.66%, P=0.188) and live birth rate (45.22% vs 43.21%, P=0.394) than did the HRT group, but these differences were not statistically significant. Moreover, endometrial thickness was significantly greater in the NC group (9.91±2.05 mm vs 8.95±1.53 mm, P Conclusion Our study shows a trend towards higher pregnancy rate and live birth rate for NC compared to HRT. Large randomized controlled trials are warranted to confirm this trend. Additionally, NC is safer than HRT, avoiding ectopic pregnancy and adverse obstetric outcomes.

26. MAJOR FACTORS INVOLVING AN IMPLANTATION RATE OF PGT-A EUPLOID EMBRYOS IN EGG DONATION PROGRAM OVER 35 YEARS

Introduction A potential impact of PGT-A on embryo implantation is often discussed in the reproduction of elderly women with a higher risk of oocyte aneuploidy while its impact is belied in women under 35 years at the same time. The authors studied the influence of PGT-A in egg donation program where the advanced reproductive age and potential oocyte incompetence is mostly excluded. Material and methods In total, 246 embryos were thawed and transferred in egg donation patients of the age category 35 plus in period January 2017 – December 2018. Group A consists of 188 patients with a comprehensive aneuploidy screening (PGT-A), group B consists of 58 patient with no PGT-A. There were performed elective single embryo transfers solely in both groups. Results In group A an implantation rate was 46% (86/188) while in group B 20%(12/58). Natural cycles with triggering ovulation were more successful than the HRT ones (IR 53% resp. 44%). Conclusions The results showed that PGT-A and transfer of euploid embryo improve an implantation rate in egg donation program in the age category 35 plus what is usually disregarded. The number of cycles to pregnancy was lower in case of a euploid embryo was transferred. The major factors involving the implantation rate besides the embryo quality and euploidy are an appropriate endometrial quality and striking the window of implantation (WOI). The implantation rate is slightly better in natural cycles compared to HRT (hormonal replacement treatment) cycles. Among other factors, we reached better results using a longer progesterone administration (minimum 5 days) and a time-lapse monitoring system used in synergy with an embryo selection for the biopsy. A potential impact of PGT-A on embryo implantation is often discussed in the reproduction of elderly women with a higher risk of oocyte aneuploidy while its impact is belied in women under 35 years at the same time. The authors studied the influence of PGT-A in egg donation program where the advanced reproductive age and potential oocyte incompetence is mostly excluded. In total, 246 embryos were thawed and transferred in egg donation patients of the age category 35 plus in period January 2017 – December 2018. Group A consists of 188 patients with a comprehensive aneuploidy screening (PGT-A), group B consists of 58 patient with no PGT-A. There were performed elective single embryo transfers solely in both groups. In group A an implantation rate was 46% (86/188) while in group B 20%(12/58). Natural cycles with triggering ovulation were more successful than the HRT ones (IR 53% resp. 44%). The results showed that PGT-A and transfer of euploid embryo improve an implantation rate in egg donation program in the age category 35 plus what is usually disregarded. The number of cycles to pregnancy was lower in case of a euploid embryo was transferred. The major factors involving the implantation rate besides the embryo quality and euploidy are an appropriate endometrial quality and striking the window of implantation (WOI). The implantation rate is slightly better in natural cycles compared to HRT (hormonal replacement treatment) cycles. Among other factors, we reached better results using a longer progesterone administration (minimum 5 days) and a time-lapse monitoring system used in synergy with an embryo selection for the biopsy.

Relationship of Migraine and Tension-Type Headache With Hypothyroidism: A Literature Review.

Migraine, tension-type headache, and hypothyroidism constitute very common medical conditions. Headache is one of the most common symptoms of hypothyroidism, occurring in approximately one-third of the patients. To date, data about the relationship between migraine and tension-type headache and thyroid dysfunction, and in particular hypothyroidism have been contradictory, while the underlying pathophysiological basis explaining this association is still unclear. In this review, we investigated the association between primary headaches and hypothyroidism, with the aim of shedding light on its pathophysiological basis. We conducted a systematic search in the MEDLINE database using both subject headings and keywords for headache, migraine, tension-type headache, thyroid hormones, and hypothyroidism, and we also examined manually the reference lists of all articles that met the inclusion criteria. Included studies were related to headache and thyroid disease comorbidity, with emphasis on hypothyroidism (ideally demonstrated by hormonal measurements), and with the term headache including migraine, tension-type headache, and headache attributed to hypothyroidism (HAH) based on the International Classification of Headache Disorders IIIb. Quality of studies was assessed by the Newcastle-Ottawa scale. Of a total of 640 identified articles, 9 studies were included. Overall, there was vast heterogeneity across the included studies concerning population, study design and outcomes. Two studies investigated the HAH, with emphasis on the clinical characteristics of headache (time of onset, localization, quality, intensity, and response to hormonal replacement treatment). Five studies investigated comorbidity between migraine and thyroid disorders, especially hypothyroidism, and in the majority of them a positive association was demonstrated. One study found that headache, and particularly migraine, may increase the risk of developing hypothyroidism. Finally, only 1 study on chronic tension-type headache found coexistence of migraine and hypoactivity of the hypothalamus-pituitary-thyroid axis. The strengths and limitations of these studies are analyzed and possible pathophysiological mechanisms are suggested. The existing data are considered inadequate to answer with certainty the relationship between headaches and thyroid disorders. According to our analysis, it seems that suggestions for a possible bidirectional association between headaches and especially migraine and hypothyroidism could exist. It hence lays the foundation for further research into the aforementioned association and its pathogenesis via large prospective multicenter studies.

Weekly intramuscular progesterone for luteal phase support in women receiving oocyte donation is associated with a decreased miscarriage rate.

To determine whether adding intramuscular to vaginal administration of progesterone reduces miscarriage rates compared with those of vaginal administration alone for luteal phase support in women receiving oocyte donation and to determine the best time to introduce intramuscular progesterone. Retrospective analysis of miscarriage rates in women receiving oocyte donation. Recipients underwent endometrial preparation by hormone replacement treatment. Vaginal progesterone alone or associated with intramuscular progesterone was used for luteal support. This study analysed 186 oocyte donation cycles from January 2016 to May 2018 with embryo transfer on Day 2 or 3 and vaginal progesterone administration: 106 embryo transfer cycles with vaginal progesterone alone, 29 with weekly intramuscular progesterone added once the human chorionic gonadotrophin (HCG) assay was positive, and 51 with weekly intramuscular progesterone added the evening of embryo transfer. The rates of positive HCG assays, biochemical pregnancies and clinical pregnancies did not differ between the treatment groups. The miscarriage rate was significantly lower when intramuscular progesterone began the evening of embryo transfer than with vaginal administration alone (16.7% versus 47.0%, respectively; P = 0.049 after Bonferroni correction). The live birth rate was higher when intramuscular progesterone began the evening of embryo transfer than with vaginal administration alone (37.3% versus 16.0%, respectively; P = 0.009 after Bonferroni correction). Adding intramuscular to vaginal progesterone administration appears to decrease the miscarriage rate and increase the live birth rate in oocyte donations. The initiation of intramuscular progesterone is most beneficial when it is introduced the evening of embryo transfer.

A Rare Case of Swyer Syndrome

Swyer syndrome is caused by abnormal sex differentiation during the embryonic period, resulting in incomplete intrauterine masculinization and undifferentiated gonads. The present case report describes a patient with Swyer syndrome associated with gonadoblastoma. At age of 16 years, this patient reported with primary amenorrhea at Gynae Department of the BIRDEM general Hospital. A physical examination revealed that the patient was at Tanner stage 4 with respect to axillary hair, breasts and pubic hair; she had normal vagina and a small cervix. As her examination findings revealed normal, she was referred to Endocrine outpatient (OPD) for further evaluation. Her karyotyping revealed 46XXY, abdominal ultrasonography revealed adnexal tumor in both sides. On laparotomy, complex tumor was found in both adnexal regions and both ovaries were resected and histopathology revealed gonadoblastoma. The patient was subjected to subsequent chemotherapy. She was treated with a combination of estrogens and progestogens to induce cyclical bleeding, which she discontinued after 3 years. She was lost to follow up for 16 years and again reported to endocrine OPD with irregular menstrual bleeding. Presence of any residual gonadal functional tissue was searched both biochemically and by imaging and the result was negative. Her menstruation was stopped by progestogens and which later on withdrawn successfully without any further onset of menstruation. In conclusion, this report describes an extremely rare case of Swyer syndrome with gonadoblastoma and spontaneous menstruation after a long period of discontinuation of hormone replacement treatment.&#x0D; Birdem Med J 2019; 9(2): 174-176

Review of Hormone Replacement Therapy in Girls and Adolescents with Hypogonadism.

Girls with either hypo- or hypergonadotropic hypogonadism need treatment with estrogens to initiate puberty and maintain a normal hormonal milieu. The focus of this review is hormone replacement treatment in girls with hypogonadism, to initiate and progress through puberty, and to maintain a healthy hormonal milieu in women. It also addresses what is known in the literature regarding estrogen levels in girls and women, instructive cases, practical tables for reference and application, and thoughts on future directions in this area. It represents a thorough literature review with author opinions and recommendations. Girls with normal ovarian function begin puberty on average at 10.5years old, although there is variation according to ethnicity and degree of excess weight gain. The aim of estrogen therapy to initiate puberty is to mimic normal onset and rate of progression. On the basis of the currently available literature, when a diagnosis of hypogonadism is established, we recommend initiating treatment between age 11 and 12years of age, with dose increases approximately every 6months until adult levels are reached. In some situations, treatment may be delayed to allow time for diagnosis or permit more time for linear growth, or address unique risks found in girls treated for various cancers or blood disorders. When adult dosing is reached, progestins are also used to protect uterine health. This can be combined sequentially, allowing regular menstruation, or combined continuously when menstrual bleeding is not preferred. Treatment is continued until the average age of menopause, again with various considerations for longer or shorter duration on the basis of risk-benefit ratios. Transdermal estrogens are considered the most physiologic replacement and theoretically might have fewer associated risks. We review what is known about risks and outcomes and areas for future research.

A Comparison of the Miscarriage and Live Birth Rate for Frozen Embryo Transfer According to Two Endometrial Preparations: Natural or Primed with Estrogens

Objective The primary objective is to compare miscarriage rates in frozen-thawed embryo transfer (FET) cycles, according to the endometrial preparation used either artificial through the administration of exogenous estrogen and progesterone or natural without any treatment, during a spontaneous ovulatory cycle. The secondary objective is to compare the live birth rates between the two endometrial preparations. Study design This is a retrospective study done at KK Women’s and Children’s Hospital Singapore. We included women who underwent FET cycles either with hormone replacement treatment (HRT) or no treatment (natural) for the endometrial preparation, regardless of their cycle number, from 1 January 2011 till 31 December 2015. Results A total of 2,752 FET cycles were included in our analysis. The natural cycle followed by vaginal progesterone support was used in 1,221 cycles and the HRT cycle with estrogen and vaginal progesterone was used in 1,531 cycles. There is a significantly higher miscarriage rate in the HRT group (38.4%) compared with the natural group (22.3%). The live birth rate is significantly higher in the natural group (22.8%) compared with the HRT group (17.3%). The multivariate analysis further shows that the HRT therapy is independently associated with an increased risk of miscarriage (adjusted odds ratio 2.05; 95% confidence interval 1.45–2.90; [Formula: see text] &lt;0.001) and hence lower odds of live birth (adjusted odds ratio 0.69; 95% confidence interval 0.56–0.84; [Formula: see text] &lt;0.001) after adjusting for the patient’s age at which the embryo was cryopreserved, race, body mass index, main indications for in vitro fertilization, number of embryos transferred and type of embryo transferred. Conclusion We have shown in this study that the miscarriage rate is higher in the HRT FET group and that this increased miscarriage rate translates into a lower live birth rate in the HRT group. Thus, we conclude that patients with regular menstrual cycles should be offered a natural FET cycle to achieve better outcomes in terms of live birth rate and reducing the miscarriage rate.

POST-MENOPAUSAL BREAST ARTERIAL CALCIFICATIONS (BACS) IN WOMEN AS A POSSIBLE BIOMARKER FOR INCREASED RISK OF DEVELOPING DEMENTIA: STUDY RATIONALE, DESIGN, AND METHODOLOGY

Introduction Although historically considered two distinct entities, both vascular dementia (VD) and Alzheimer's Dementia (AD) are associated with increased odds of cerebrovascular disease. While early-onset AD ( To address the findings that peripheral artery disease (PAD) and AS play a key role in the development of both VD and AD, we plan to determine the relationship between BACs and dementia. We hypothesize that women with dementia have more severe BACs than healthy controls. Methods This is a multisite (UCLA Health, West Los Angeles VA Medical Center) study involving review of electronic medical records (EMRs) at these two affiliated institutions. Our primary objectives are to (1) evaluate whether higher degrees of BACs correlate with clinical diagnosis of dementia, and (2) validate screening mammograms as biomarkers for identifications of women at risk of dementia. Secondary objectives are to (1) evaluate whether higher degrees of BACs correlate with greater WMD on brain MRIs, and (2) identify contributing metabolic factors to BACs as potential targets for prevention of AS and therefore dementia. We will extract data from EMRs of post-menopausal women 50 years and older with a diagnosis of dementia over the past 10 years and sex/age-matched controls without dementia. All women will have undergone mammogram within two years of dementia diagnosis. We anticipate approximately 800 subjects. The following characteristics will be analyzed as co-variates/confounding factors: chronic kidney disease, diabetes, osteoporosis, hormone replacement treatment, vitamin D level, estrogen level, BMI as well as h/o smoking, stroke and/or TIA, depression, and head trauma. For imaging analysis, degree of BACs will be scored using a four-point scale, considering severity and extent of calcifications (see Figure). For women with brain MRI scans available within one year of the mammogram study date, degree of WMD will also be scored on a four-point scale according to the Fazekas (AJR. 1987;149:351-6) score. For statistical analysis, we will first compare women with dementia and controls on demographics to ensure that they are well-matched, or identify variables to use as covariates in the analyses. Calcification burden will be compared between these subject groups using t-tests or ANCOVAs (if covariates are needed). For women with MRI scans, we will use chi-squared or Fisher's exact tests to test for associations between calcification burden and WMD. Results This study recently received IRB approval from one of the two participating sites and is pending IRB review from the second site. Preliminary data are estimated to be available for presentation at the time of the 2018 Annual Meeting. Conclusions Previous reports indicate that the prevalence of mammographically-detected BACs can be as high as 29%. In clinical practice, however, BACs are not consistently reported because are considered “incidental findings” having no relation to breast malignancy. A 2014 meta-analysis demonstrated a strong association between BACs and cardiovascular disease. In a recent 2018 autoptic study (Overisgaran et al. Acta Neuropathol. 2018 Oct 17. doi: 10.1007/s00401-018-1920-1) including postmortem data from 1453 individuals concluded that women had higher levels of AD pathology as well as more severe arteriolosclerosis. While there are other more invasive methods to assess AS, mammograms can provide a simple and readily available and provide longitudinal “snap-shots” of PAD in asymptomatic women and may help elucidate the relationship between medial artery sclerosis as a separate entity in increasing risk for cognitive impairment. This research was funded by UCLA Health, U.S. Department of Veterans Affairs, Semel Institute for Neuroscience & Human Behavior

Resumption of Ovarian Function After Ovarian Biopsy/Scratch in Patients With Premature Ovarian Insufficiency.

To evaluate the effect of ovarian biopsy and scratch on the resumption of ovarian function in women with premature ovarian insufficiency (POI), the follicle development and pregnancy outcome were retrospectively analyzed in women with POI after ovarian biopsy/scratch. Eighty patients with POI with secondary amenorrhea were accepted the laparoscopic surgery, and then hormone replacement treatment for 6 months was applied and in vitro fertilization and embryo transfer was suggested. No significant difference in clinical characteristics was observed before and after ovarian biopsy/scratch ( P > .05). After the ovarian surgery, 11 (13.75%) patients presented with ovarian function resumption spontaneously or with human menopausal gonadotropin stimulation. Three metaphases II oocytes were retrieved in 10 patients. Two embryos were formed and freshly transferred followed by a healthy singleton delivery in 1 (1.25%) patient. Patients with follicle development had higher baseline estradiol compared to those without (78.20 [18.53-161.08] pg/mL vs 15.70 [8.40-43.80] pg/mL, P < .01). The technique of ovarian biopsy/scratch could promote follicle development in vivo, suggesting it could bring promising benefits for some women with POI. However, future improvement in efficiency and practice criteria is warranted.

Endometrium cytokine profiles are altered following ovarian stimulation but almost not in subsequent hormone replacement cycles

PurposeTo investigate the impact of ovarian stimulation and hormone replacement treatment on key regulatory cytokines in endometrial secretion during endometrium implantation window. MethodsFifty-six patients undergoing ovarian stimulation (OS) with gonadotropin releasing hormone antagonist and frozen embryo transfer with hormone replacement treatment (HRT) were recruited. Endometrial secretion aspiration was performed repeatedly during implantation window in natural, OS and HRT cycles of every patient. The concentrations of 17 mediators, known to be involved in human embryo implantation, were assessed by multiplex immunoassay. ResultsCompared with natural cycle (NC), the concentration of IFN-γ, G-CSF and IL-8 within endometrium were almost the same following OS and HRT. Furthermore, increased MCP-1 levels were observed following HRT and OS. In addition, an increase in IL-1b, IL-7, IL-17, IL-6, TNF-a, IL-12, IL-4, IL-13, IL-10, IL-5, VEGF and MIP-1b concentrations were found in OS cycle only. The level of GM-CSF was lower in HRT cycle and higher in OS cycle, when compared with NC. Among all 17 cytokines, no correlation was found between cytokine concentrations and serum estradiol and progesterone, while only IL-7 concentration has a low correlation with serum LH level. ConclusionCompared to natural and hormone replacement cycle, patients’ endometrium cytokine profiles present an increased inflammatory response following ovarian stimulation.

Evaluation of body composition in POF and its association with bone mineral density and sex steroid levels

The study aims to investigate the body composition and bone mineral density (BMD) characteristics and discuss the relationships among body composition, BMD and sex steroid level in POF. A total of 240 POF patients, 240 normal women, and peri/postmenopausal women (Peri-M/Post-M) (260 patients in each group) were included. Compared to the control group, POF patients? strength of left/right lower limb (SLL/SRL), muscle distributing coefficient of lower limbs (MD) decreased however, waist circumference (WC) and hip circumference (HC) increased. The weight, WC, HC, whole body fat percentage (BF%), average fat distribution (FD), MD of POF patients were lower than those among Peri-M and Post-M and BMD were lower than the Peri-M, yet still higher than Post-M. Moreover, BMD were significantly positively correlated with BF%, FD, SLL, MD and estradiol (E2). The factors associated with L2–L4 BMD were E2, SRL, FD and age. For the FN BMD, the factors were FD, E2 and SLL. Therefore, we conclude that maintenance of appropriate weight, physical exercise and hormone replacement treatment (HRT) may have positive effects on increasing BMD, improving muscle mass and muscle strength, preventing osteoporosis.

The Effect of Tamoxifen on Thin Endometrium in Patients Undergoing Frozen-Thawed Embryo Transfer.

Tamoxifen has played a vital role in endocrine therapy for the treatment of estrogen receptor-positive breast cancer. We examined the effect of tamoxifen in patients with a thin endometrium in frozen-thawed embryo transfer (FET) cycles and compared the improvement in endometrial thickness (EMT) and pregnancy outcomes stratified by different etiologies of thin endometrium. A total of 226 women were recruited for a new tamoxifen protocol; all had an EMT of less than 7.5 mm in previous cycles, including natural cycle (NC), hormone replacement treatment (HRT), and ovulation induction (OI) cycles. Compared with previous cycles, tamoxifen cycles showed a significantly increased EMT (from 6.11 ± 0.98 mm to 7.87 ± 1.48 mm in the NC group, from 6.24 ± 1.01 mm to 8.22 ± 1.67 mm in the HRT group, and from 6.34 ± 1.03 mm to 8.05 ± 1.58 mm in the OI group; all P < .001). Patients were further divided into 3 groups based on the causes of their thin endometrium: (1) history of intrauterine adhesion (n = 34), (2) history of uterine curettage (n = 141), and (3) polycystic ovary syndrome (PCOS; n = 51). Patients with PCOS obtained the thickest EMT (9.31 ± 1.55 mm), the lowest cycle cancellation rate (11.76%), and the highest rate of clinical pregnancy (60%) and live birth (55.56%) per transfer ( P < .001). Multivariable regression analysis showed that EMT was related to live birth (odds ratio: 1.487; 95% confidence interval: 1.172-1.887). A tamoxifen protocol improves EMT in patients after NC, HRT, and OI cycles during FET. Patients with PCOS show the most benefit from tamoxifen and achieve better pregnancy outcomes.