Hormone Replacement Protocol Research Articles

P-614 The use of home ovulation prediction kits (OPKs) in true natural cycle frozen embryo transfer (NC FET)

Abstract Study question Do urinary OPKs have inferior ability to detect the LH surge compared to daily serum monitoring among patients undergoing true NC FET? Summary answer OPKs are highly accurate and may serve as reliable tests to detect the LH surge among patients undergoing NC FET. What is known already Frozen embryo transfers continue to increase worldwide and recent evidence suggests natural cycle protocols may be superior to hormone replacement protocols because of lower risk of miscarriage and lower risk of pregnancy complications. Patients undergoing NC FET attend multiple clinic appointments which has been associated with increased patient stress levels during fertility treatment. OPKs have been found to be accurate at detecting the LH surge in the trying to conceive population and have high user acceptability. Study design, size, duration A prospective single cohort study including 139 fertility seeking participants was completed at an academic-affiliated fertility center for a duration of 12 months. Participants/materials, setting, methods Patients scheduled for NC FET (regular cycles 27-35 days, mid luteal progesterone >30 nmol/L, no luteal phase concern) with the ability to provide informed consent and access to SMS texting devices were eligible for participation. On the same day they started daily morning bloodwork as per the standard protocol (2-3 days prior to anticipated LH surge), participants began twice daily OPK testing. Upon exiting the study, patients completed a questionnaire on satisfaction with OPK use. Main results and the role of chance LH surge detection rate was 85.6% (n = 119/139) with serum monitoring and 93.5% (130/139) with OPK use (Kappa agreement 90.7%, K = 0.51, p < 0.001). Among patients with a serum-detected LH surge, OPK was positive within +/- 12 hours of the serum LH surge detection in 84.8% of patients. In 23.7% of cycles, OPK was positive the same morning as serum blood work. In 27.1% of cycles, OPK was positive 12h prior and in 33.9% of cycles, OPK was positive 12h after serum LH surge detection. Actual NC FET cycle cancellation rate was 16.6% (n = 23/139) compared to an anticipated cycle cancellation rate of 20.9% (29/139) if OPKs had been used to initiate serum monitoring. The average reduction in the number of serum monitoring visits and distance travelled in kilometers with OPK use was 3.9 visits (SD 2.1) and 155km (SD 174), respectively. The majority of participants reported satisfaction with OPK use. Of 135 patients, 110 (81.5%) strongly agreed the OPK was easy to use, 100 (74.1%) strongly agreed they would be open to using OPKs in future fertility treatments and 120 (88.9%) reported a reduction or no impact on stress levels associated with fertility treatments. Limitations, reasons for caution This study only used Clearblue Digital Ovulation Tests and the reported reliability in our study cannot be extrapolated to all OPKs. Additionally, the accuracy of the reported serum LH surge detection rate may be limited by physician specific definitions of serum LH surge. Wider implications of the findings OPKs are highly accurate and may serve as a reliable trigger for serum monitoring in NC FET. While their use would reduce the number of clinic appointments and distance travelled for patients undergoing NC FET cycles, patients should be advised OPK use may be associated with higher cycle cancellation rates. Trial registration number Not applicable

Endometrial pattern predicts pregnancy outcome in single-blastocyst frozen-embryo transfer: An analysis of 1383 cycles.

Several studies investigated endometrial patterns, with respect to pregnancy rates following the transfer of embryos but did not distinguish between single- and multiple-blastocyst procedures. We clarified how the endometrial pattern imaged to transfer a frozen embryo is associated with pregnancy outcomes in single-blastocyst frozen-embryo transfer (sbFET). Patients ≤35 years who underwent sbFET on the hormone replacement protocol. We analyzed endometrial patterns' associations with pregnancy outcomes in relation to blastocyst grade and pregnancy-related factors. Of the 1383 cycles, 483 were Lf, 840 were partial-Lf, and 60 were non-Lf. Leaf pattern (Lf): central echogenic line present and continuous. Overall, decreasing distinctness of the central echogenic line was associated with significantly lower rates of clinical pregnancy (Lf: 70.4%; partial-Lf: 58.1%; non-Lf: 28.3%) and live birth (56.3%, 45.5%, and 15.0%) and a higher miscarriage rate (20.0%, 21.7%, and 47.1%). Logistic regressions showed pregnancy and live birth to be significantly more likely and miscarriage less likely in Lf than non-Lf: OR (95% CI): 6.07 (3.24-11.37), 7.43 (3.47-15.39), and 0.20 (0.07-0.57). Non-Lf presentation was associated with lower rates of pregnancy and live birth, suggesting it signals unsuitable conditions for embryo transfer. We provide information on the pregnancy outcomes of sbFET for endometrial patterns.

Effects of Hormone Replacement Therapy on Bone Mineral Density in Korean Adults With Turner Syndrome.

Turner syndrome (TS) is a common chromosomal abnormality, which is caused by loss of all or part of one X chromosome. Hormone replacement therapy in TS is important in terms of puberty, growth and prevention of osteoporosis however, such a study has never been conducted in Korea. Therefore, the purpose of our study was to determine relationship between the starting age, duration of estrogen replacement therapy (ERT) in TS and develop a hormone replacement protocol suitable for the situation in Korea. This is retrospective study analyzed the medical records in TS patients treated at the Severance hospital, Yonsei University College of Medicine, Seoul, Korea from 1997 to 2019. Total of 188 subjects who had received a bone density test at least once were included in the study. Korean National Health and Nutrition Examination Survey (KNHANES) was used for achieving bone mineral density (BMD) of normal control group. Student's t-test, Mann-Whitney U test, ANOVA and correlation analysis were performed using SPSS 18.0. Each BMD measurement was significantly lower in women with TS than in healthy Korean women. Early start and longer duration of ERT is associated with higher lumbar spine BMD but not femur neck BMD. Femur neck BMD, but not lumbar spine BMD was significantly higher in women with mosaicism than 45XO group. Early onset and appropriate duration of hormone replacement therapy is important for increasing bone mineral density in patients with Turner syndrome. Also, ERT affects differently to TS patients according to mosaicism.

O-221 Regenerative endometrial PRGF (plasma rich in growth factors) treatment in patients with thin endometrium, recurrent implantation failure, and recurrent miscarriages: a retrospective, self-controlled, cohort study

Abstract Study question What reproductive outcomes are observed in patients submitted to endometrial PRGF therapy due to thin endometrium (ThE), recurrent implantation failure (RIF) and recurrent miscarriages (RM)? Summary answer Following endometrial PRGF treatment, success rates were significantly increased in ThE and RIF patients, whereas in the RM group pregnancy loss rates were not affected. What is known already Adequate development of a functional endometrium is a prerequisite for successful embryo implantation in ART cycles. In contrast, the management of patients with thin endometrial lining or recurrent implantation failure has been an ongoing challenge with none of the proposed surgical, hormonal, and pharmacological interventions achieving satisfactory results. In recent years, the use of plasma rich in growth factors (PRGF) - successfully applied in other medical fields - has become a novel treatment option in reproductive medicine. It was used experimentally both for ovarian follicle activation and to enhance endometrial receptivity although published studies are small with often contradictory results. Study design, size, duration All consecutive patients (n = 107) who underwent endometrial PRGF treatment (n = 150) in a single, private centre between 2016-2022 were included in this retrospective analysis. Patients were recruited into ThE (n = 64), RIF (n = 36) and RM (n = 7) groups, respectively. Live birth / ongoing pregnancy rates per embryo transfer were compared to success rates obtained in previous embryo transfers preceding the endometrial PRGF intervention. External Ethics Committee approval was obtained for a comparative pilot study including above patient groups. Participants/materials, setting, methods PRGF was obtained by processing the patients’ autologous blood sample in an in-house validated open system. Endometrial PRGF interventions were performed using a thawed PRGF sample with a series of intrauterine instillations (43%) or with a combined approach performing hysteroscopic subendometrial infiltration during early follicular phase (57%). Endometrial preparation was conducted using an artificial hormone replacement protocol with high-dose oral estrogens and vaginal progesterone. Most embryo transfers involved the replacement of a single, vitrified-thawed blastocyst. Main results and the role of chance A total of 107 patients underwent 150 endometrial PRGF treatments and 131 subsequent embryo transfers. Altogether 19 (13%) embryo transfers were cancelled, higher in ThE than in the RIF group (16 vs 7.1%). In the ThE group (64 patients, 98 PRGF cycles and 107 controls), positive pregnancy (41 vs 32%, NS), clinical pregnancy (35 vs 22%, p = 0.049) and ongoing pregnancy/live birth rates (24 vs 4.7%, p < 0.0001) per embryo transfer were significantly higher in the endometrial PRGF treatment group compared to previous embryo transfers. In the RIF group (36 patients, 42 PRGF cycles and 101 controls), positive pregnancy (59 vs 20%, p < 0.0001), clinical pregnancy (44 vs 11%, p < 0.0001) and ongoing pregnancy/live birth rates (33 vs 7.9%, p < 0.0001) per embryo transfer were significantly higher in the endometrial PRGF treatment group compared to previous embryo transfers. In the RM group (7 patients, 10 PRGF cycles and 15 controls), positive pregnancy (50 vs 60%), clinical pregnancy (20 vs 27%) and ongoing pregnancy/live birth rates (0 vs 0%) per embryo transfer were not significantly different and no ongoing pregnancies were achieved. So far, 20 singletons and 1 set of twins have been confirmed to be born from the above PRGF cycles (12 pregnancies still ongoing). Limitations, reasons for caution Heterogeneity of clinical severity between included ThE patients could affect observed reproductive outcomes. The self-controlled design of the study might have influenced the comparison between pre-, and post-intervention pregnancy rates, although this also highlights the poor-prognostic nature of included participants. RM patients were too few to evaluate pregnancy loss rates. Wider implications of the findings This preliminary, retrospective study has shown that regenerative therapy using autologous PRGF is a safe, affordable, and efficient treatment option for ThE and RIF patients. Further randomized studies are warranted, although they are hampered by patient selection issues and the lack of applicable efficient treatment options in the non-intervention group. Trial registration number not applicable

Evaluation of Early Frozen Blastocyst Transfer in A True Natural Cycle Protocol in Comparison to A Hormone Replacement Protocol: A Single-Center Cohort Study.

Timing of frozen embryo transfer (FET) within a purported window of implantation is of increasing interest, and there is a paucity of evidence surrounding the transfer of frozen embryos early within these frozen embryo transfer protocols. This study aimed to evaluate whether live birth rates were equivalent after FET of blastocysts 4 days after luteinizing hormone (LH) surge in a true natural cycle protocol, compared to a hormone replacement (HR) protocol. Single-centre, retrospective cohort study involving patients undergoing autologous frozen blastocyst transfer from January 1st, 2013, to December 31st, 2016. Cycles were grouped according to their protocol: true natural cycle (hormonal detection of LH surge with FET scheduled four days later) versus HR cycle (luteal phase gonadotropin-releasing hormone agonist suppression, oral or vaginal estradiol and intramuscular progesterone starting five days before FET). A total of 850 cycles were included, 501 true natural cycles and 349 HR cycles. The primary outcome was the live birth rate, secondary outcomes included clinical pregnancy rate and miscarriage. Logbinomial regression models were performed adjusting for a priori selected variables. Adjusted resulted in live birth rates of 38.7 and 40.4%, [adjusted risk ratio (aRR): 0.96, 95% confidence interval (CI): 0.76-1.22, P=0.729] in the natural cycle and HR groups, respectively. The secondary outcome analyses did not demonstrate any statistically significant difference in the rate of positive human chorionic gonadotropin (hCG), clinical intrauterine pregnancy rate, or miscarriage rate. The timing of the FET four days after LH surge in a true natural cycle protocol results in equivalent live birth rates compared to a HR protocol. Results of this study suggest that the window of implantation within the natural cycle may be less finite than currently believed and further prospective studies evaluating the timing of frozen embryo transfer are warranted.

P-387 Autologous Platelet-Rich Plasma (PRP) intrauterine infusion before embryo transfer could improve the treatment outcomes, especially for transferring euploid blastocysts, in recurrent implantation failure patients

Abstract Study question Is the intrauterine infusion of autologous PRP prior to embryo transfer, especially euploid blastocyst transfer, effective in solving recurrent implantation failure? Summary answer Autologous PRP intrauterine infusion before embryo transfer (ET), especially before transferring euploid blastocysts, could improve the treatment outcomes in RIF patients. What is known already Firstly, autologous PRP intrauterine infusion has been proposed to improve the outcomes of ET in patients having thin endometrium or a history of RIF. Hypothetically, growth factors and cytokines in PRP assist in preparing endometrium surface as well as conducting critical early molecular signaling pathways between the embryos and the uterus. We have developed and optimized a specific PRP infusion protocol for RIF (presented at ESHRE 2021, P-428). Secondly, various reports have suggested that transferring euploid blastocysts have better results than unscreened ones. Here we evaluate the effects of PRP infusion, together with transferring euploid blastocysts in RIF treatment. Study design, size, duration From 11/2020 - 07/2021, all patients who had one PRP infusion before ET were recorded (n = 130). RIF patients were classified as follows: group A (unscreened blastocysts, n = 51 patients) included having at least two ET failures (beta-hCG < 5 IU/L). The embryos in this group did not undergo preimplantation genetic testing for aneuploidy (PGT-A). Group B (euploid blastocysts, n = 50 patients) were cases having at least one ET failure using euploid blastocysts previously screened by PGT-A. Participants/materials, setting, methods Endometrium preparation was followed hormone replacement protocol using E2 and P4 with autologous PRP infusion 48 hours before ET. All ETs in this study were frozen blastocyst ones. Apart from groups A and B, a small group of patients (n = 29) might not have previous unsuccessful ET but had relatively thin endometrium (< 9 mm), hence requiring PRP treatment. Beta-hCG, yolk sac and clinical pregnancy outcomes were recorded. A Chi-square test was applied. Main results and the role of chance 76/130 patients in this study had beta-hCG positive (58.5%). Here, we focused on RIF, therefore only data of groups A and B were analyzed (n = 29 cases without previous ET failures excluded). In group A (n = 51), 26 cases had beta-hCG positive (51%); 21 cases (41.2%) had yolk sac and then clinical pregnancy; five cases had only biochemical pregnancy. In group B (n = 50), 26 cases had beta-hCG positive (52%), 23 cases had gestational sac and then clinical pregnancy (46%); three cases had biochemical pregnancy. PRP infusion had positive impacts on implantation (all groups had >50% beta-hCG positive). The rates of beta-hCG positive in groups A and B were both lower than this rate in total patients suggesting that relatively thin endometrium (< 9 mm) may not critically require PRP infusion. The beta-hCG rates of groups A and B were statistically indifferent (p > 0.05). However, group B had higher average age than group A (37.7 ± 6.5 vs 33.06 ± 4.92), and had several poorer prognosis patients such as patients having low AMH, endometriosis or hydrometrocolpos. This result implied that PGT-A could help older and poorer prognosis RIF patients equal treatment outcomes with the younger and better prognosis RIF patients. Limitations, reasons for caution There were fewer biochemical pregnancy events in group B than group A (three vs. five), however, the study had a small sample size requiring ongoing enrolment to confirm this conclusion. This is impossible for this type of intervention study to have control (a group without PRP infusion). Wider implications of the findings On the side of the endometrium, PRP intrauterine infusion showed positive effects in assisting RIF patients to have implantation. On the embryo's side, embryo selection, especially PGT-A for euploid ones, could critically contribute to successful implantation and pregnancy. Trial registration number Not applicable

Sex-specific neurobiological actions of prophylactic (R,S)-ketamine, (2R,6R)-hydroxynorketamine, and (2S,6S)-hydroxynorketamine.

Enhancing stress resilience in at-risk populations could significantly reduce the incidence of stress-related psychiatric disorders. We have previously reported that the administration of (R,S)-ketamine prevents stress-induced depressive-like behavior in male mice, perhaps by altering α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)-mediated transmission in hippocampal CA3. However, it is still unknown whether metabolites of (R,S)-ketamine can be prophylactic in both sexes. We administered (R,S)-ketamine or its metabolites (2R,6R)-hydroxynorketamine ((2R,6R)-HNK) and (2S,6S)-hydroxynorketamine ((2S,6S)-HNK) at various doses 1 week before one of a number of stressors in male and female 129S6/SvEv mice. Patch clamp electrophysiology was used to determine the effect of prophylactic drug administration on glutamatergic activity in CA3. To examine the interaction between ovarian hormones and stress resilience, female mice also underwent ovariectomy (OVX) surgery and a hormone replacement protocol prior to drug administration. (2S,6S)-HNK and (2R,6R)-HNK protected against distinct stress-induced behaviors in both sexes, with (2S,6S)-HNK attenuating learned fear in male mice, and (2R,6R)-HNK preventing stress-induced depressive-like behavior in both sexes. (R,S)-ketamine and (2R,6R)-HNK, but not (2S,6S)-HNK, attenuated large-amplitude AMPAR-mediated bursts in hippocampal CA3. All three compounds reduced N-methyl-D-aspartate receptor (NMDAR)-mediated currents 1 week after administration. Furthermore, ovarian-derived hormones were necessary for and sufficient to restore (R,S)-ketamine- and (2R,6R)-HNK-mediated prophylaxis in female mice. Our data provide further evidence that resilience-enhancing prophylactics may alter AMPAR-mediated glutamatergic transmission in CA3. Moreover, we show that prophylactics against stress-induced depressive-like behavior can be developed in a sex-specific manner and demonstrate that ovarian hormones are necessary for the prophylactic efficacy of (R,S)-ketamine and (2R,6R)-HNK in female mice.

GnRH antagonist for endometrial priming in an oocyte donation programme: a prospective, randomized controlled trial.

Can gonadotrophin releasing hormone (GnRH) antagonist be used in egg donation recipients with ovulatory cycles for the purpose of achieving synchronization between the donor´s and recipient´s cycle? Prospective randomized controlled trial to compare 7-day dosage of GnRH antagonist for endometrial priming in an oocyte donation programme with a single dose of long-acting GnRH agonist. A total of 563 women were randomized in a private single centre, and 473 women underwent embryo transfer. Ongoing pregnancy rate was the primary end point. Analysis was adjusted for embryonic stage at the time of embryo transfer; data collected included days on the waiting list; number of fresh-vitrified oocytes collected; and oocyte donor´s age at the time ofretrieval. No statistically significant differences were found between groups in per intention-to-treat analysis: adjusted OR 1.42 (CI 0.97 to 2.09); per treatment received: adjusted OR 1.43 (CI 0.97 to 2.09); per embryo transfer: adjusted OR for ongoing pregnancy rate 1.47 (CI 1.01 to 2.13), P = 0.047. For women with ovulatory cycles undergoing oocyte donation, the outcomes are similar between GnRH antagonist and down-regulated hormonereplacementprotocols.

Pinopode score around the time of implantation is predictive of successful implantation following frozen embryo transfer in hormone replacement cycles

Is pinopode measurement of any prognostic value? Pinopode expression was significantly associated with the occurrence of pregnancy after frozen embryo transfer. Pinopodes are expressed in the endometrium during the implantation period. Pinopode measurement has been proposed as a marker of endometrial receptivity. A prospective cohort study was conducted at the Center of Reproductive Medicine, Sir Run Run Shaw Hospital, between 2014 and 2016, recruiting 172 women with infertility and undergoing frozen embryo transfer following IVF treatment. Among 172 participants, 46 women took part in the first study to quantify the daily changing pattern of pinopodes 3-7 days after the initiation of progesterone therapy in the hormone replacement cycles and the remaining 126 women with infertility participated in a study to examine the relationship between pinopode count and pregnancy outcome following frozen embryo transfer in hormone replacement cycles. The mean age of participants was 29 years old. All participants received an artificial hormone replacement protocol capable of supporting successful implantation. Endometrial biopsies from 46 women were obtained 3, 4, 5, 6 and 7 days after the initiation of progesterone therapy (P + 3, n = 6; P + 4, n = 6; P + 5, n = 11; P + 6, n = 13; P + 7, n = 10, respectively). Another 126 endometrial biopsies were obtained precisely 6 days after the initiation of progesterone. Scanning electron microscopy was used to capture the pinopode images, followed by use of the image J program to quantify the count and subtype of the pinopodes. We found that at least 60 microscopic fields were necessary to achieve a reproducible result. An intra-observer variability study showed good agreement between two measurements regarding the developing pinopode (DP) subtype (r = 0.95) and the fully developed pinopode (FDP) subtype (r = 0.86) but not for the regressing (RP) pinopode subtype (r = 0.39). The proportion of DP/total pinopodes (TP) declined rapidly form day P + 4 to a minimum on day P + 6. The percentage of FDP/TP increased rapidly from day P + 4 to reach a peak on day P + 6. On the other hand, the percentage of RP/TP reached a peak on day P + 7. Participants who conceived had a significantly (P = 0.011) higher percentage of FDP/TP on day P + 6 and significantly (P = 0.005) lower percentage of DP/TP on the same day compared with participants who did not become pregnant. Using a scoring system incorporating the percentages of DP and FDP, it was found that the pregnancy rate and the embryo implantation rate of women with a high pinopode score (82.3%; 63.0%) was significantly (P = 0.001; P = 0.046) higher than that of women with a low pinopode score (53.3%; 46.7%), respectively. There remains a possibility that the observations could have arisen due to chance. This study examined pinopode count and subtype in the HRT cycles, and it is uncertain whether the same observations apply to in natural cycles. Pinopodes have been questioned as a potential marker of endometrial receptivity for many years. Our results suggested that pinopode measurement may be of value in predicting pregnancy. The study was supported by the grants from the general project of medicine and health in Zhejiang Province of China (2015KYA142; 2018KY106), the Key Research and Development Program of Zhejiang Province (2017C03022) and the National Natural Science Foundation of China (81701514).The funders had no role in the study design, data collection and analysis, decision to publish or preparation of the manuscript. We have no competing interests to declare. ISRCTN26300668.

A randomized comparison of three different hormone replacement protocols for thawed blastocyst transfer

A randomized comparison of three different hormone replacement protocols for thawed blastocyst transfer

The impact of transfer time on clinical pregnancy in frozen embryo transfer cycles

To identify the critical aspects of embryo transfer that impact clinical pregnancy rates, specifically the impact of transfer time. Retrospective cohort study. All consecutive frozen embryo transfer (FET) cycles using cryopreserved blastocysts from 2007 - 2014 were reviewed. All blastocysts were of high quality, all cycles used a uniform cryopreservation technique and controlled hormone replacement protocol, and all transfers were done under ultrasound guidance. Each transfer was scored on a set of standardized metrics including cohort score (morphologic appearance at transfer), ease of mock transfer, bends placed in catheter, presence of blood or mucus, and overall difficulty of transfer. Transfer time (total seconds from when the catheter was loaded until the embryo(s) was expelled into the uterine cavity) was recorded.Logistic regression models using generalized estimating equations were fit to investigate the relationship between transfer time and clinical pregnancy rate (CPR) while controlling for confounders and within-person correlations in cycle outcome. Multivariate results were adjusted for age, diagnosis, cohort score, number of embryos transferred, use of an outer sheath, type of catheter used, blood inside the catheter, and physician performing the transfer. 467 women undergoing 571 FET cycles were included. Mean age was 35.9 years (22-51 ± 4.4). Overall CPR was 47.1% . The cohort was divided into tertiles by transfer time (seconds) (T1: 33-55; T2: 57-81; T3: 82-582) with mean transfer times (SD) of 47.4 (5.7), 67.1 (7.3) and 121.9 (55.1) seconds. Crude CPR was 43.9% , 48.7% and 48.7% among respective tertiles.In univariate analysis, worse cohort score (p<0.01), blood inside catheter (p=0.02), difficult mock transfer (p<0.01), and use of an outer sheath (p=0.03) were negatively associated with CPR. No association was seen between physician performing transfer (including fellows) and CPR. In multivariate regression, longer transfer time was not associated with CPR (p-trend=0.20). Using T1 as a reference, adjusted odds ratios (95% CI) were 1.26 (0.76-2.079, p=0.37) and 1.48 (0.83-2.65, p=0.18) for transfer time groups T2 and T3, respectively. After adjusting for potential confounders, this analysis found that contrary to commonly held belief, longer embryo transfer times do not negatively impact clinical pregnancy rate. Further investigation into transfer time as a predictor of IVF outcome is warranted.

Off-label use of hormones as an antiaging strategy: a review.

Given demographic evolution of the population in modern societies, one of the most important health care needs is successful aging with less frailty and dependency. During the last 20 years, a multitude of anti-aging practices have appeared worldwide, aiming at retarding or even stopping and reversing the effects of aging on the human body. One of the cornerstones of anti-aging is hormone replacement. At present, women live one third of their lives in a state of sex-hormone deficiency. Men are also subject to age-related testosterone decline, but andropause remains frequently under-diagnosed and under-treated. Due to the decline of hormone production from gonads in both sexes, the importance of dehydroepiandrosterone (DHEA) in steroid hormone production increases with age. However, DHEA levels also decrease with age. Also, growth hormone age-associated decrease may be so important that insulin growth factor-1 levels found in elderly individuals are sometimes as low as those encountered in adult patients with established deficiency. Skin aging as well as decreases in lean body mass, bone mineral density, sexual desire and erectile function, intellectual activity and mood have all been related to this decrease of hormone production with age. Great disparities exist between recommendations from scientific societies and actual use of hormone supplements in aging and elderly patients. In this article, we review actual data on the effects of age related hormone decline on the aging process and age-related diseases such as sarcopenia and falls, osteoporosis, cognitive decline, mood disorders, cardiovascular health and sexual activity. We also provide information on the efficiency and safety of hormone replacement protocols in aging patients. Finally, we argue on future perspectives of such protocols as part of everyday practice.

Are we moving toward frozen embryo transfer (FET) as the primary form of embryo transfer (ET)?

ObjectiveDuring an IVF cycle the likelihood for success depends upon the quality of the embryo, the ease with which the ET is performed, and the uterine environment. There are three groups of women in whom the uterine environment can be controlled; recipients of donor oocytes (DO), gestational carriers (GC) and recipients of frozen embryos. In all three groups, hormone replacement (HRT) protocols are used to control the uterine environment, whereas in fresh IVF cycles this is not the case.DesignWe retrospectively reviewed all fresh IVF cycles with ET, DO/GC cycles, and FET cycles from 01/01/2011-12/31/2012. Freeze all and no transfer cycles were excluded.Materials and MethodsIndividualized protocols were used for all patients undergoing fresh cycles. Egg retrieval (ER) was performed 35 hours post hCG administration. All mature oocytes underwent ICSI. Fertilization was confirmed 18-20 hours post ICSI. ET was done either 3 or 5 days post ER based on number, cell stage, and quality of the embryos. All patients were treated with corticosteroids, antibiotics, progesterone in oil, estradiol valerate and baby aspirin post ER. Specific HRT protocols were used for all DO/GC cycles and FET cycles as well as corticosteriods, antibiotics, and baby aspirin.ResultsTabled 1IVFDO/GCFETPREGNANT73/184(39.67%)30/38(78.95%)62/106(58.49%)NON-PREGNANT111/184(60.33%)8/38(21.05%)44/106(41.51%)LOSS23/73(31.50%)5/30(16.67%)24/62(38.70%) Open table in a new tab Evaluated by χ2 analysis.ConclusionBy evaluating the data by χ2 analysis the following is true: 1)It is clear that pregnancy rates are statistically better when the uterine environment is controlled p<0.001. 2) Loss rates are similar whether or not the uterine environment is controlled p=0.998. 3)The time is approaching where HRT controlled cycles may be considered to be the best choice for ET. ObjectiveDuring an IVF cycle the likelihood for success depends upon the quality of the embryo, the ease with which the ET is performed, and the uterine environment. There are three groups of women in whom the uterine environment can be controlled; recipients of donor oocytes (DO), gestational carriers (GC) and recipients of frozen embryos. In all three groups, hormone replacement (HRT) protocols are used to control the uterine environment, whereas in fresh IVF cycles this is not the case. During an IVF cycle the likelihood for success depends upon the quality of the embryo, the ease with which the ET is performed, and the uterine environment. There are three groups of women in whom the uterine environment can be controlled; recipients of donor oocytes (DO), gestational carriers (GC) and recipients of frozen embryos. In all three groups, hormone replacement (HRT) protocols are used to control the uterine environment, whereas in fresh IVF cycles this is not the case. DesignWe retrospectively reviewed all fresh IVF cycles with ET, DO/GC cycles, and FET cycles from 01/01/2011-12/31/2012. Freeze all and no transfer cycles were excluded. We retrospectively reviewed all fresh IVF cycles with ET, DO/GC cycles, and FET cycles from 01/01/2011-12/31/2012. Freeze all and no transfer cycles were excluded. Materials and MethodsIndividualized protocols were used for all patients undergoing fresh cycles. Egg retrieval (ER) was performed 35 hours post hCG administration. All mature oocytes underwent ICSI. Fertilization was confirmed 18-20 hours post ICSI. ET was done either 3 or 5 days post ER based on number, cell stage, and quality of the embryos. All patients were treated with corticosteroids, antibiotics, progesterone in oil, estradiol valerate and baby aspirin post ER. Specific HRT protocols were used for all DO/GC cycles and FET cycles as well as corticosteriods, antibiotics, and baby aspirin. Individualized protocols were used for all patients undergoing fresh cycles. Egg retrieval (ER) was performed 35 hours post hCG administration. All mature oocytes underwent ICSI. Fertilization was confirmed 18-20 hours post ICSI. ET was done either 3 or 5 days post ER based on number, cell stage, and quality of the embryos. All patients were treated with corticosteroids, antibiotics, progesterone in oil, estradiol valerate and baby aspirin post ER. Specific HRT protocols were used for all DO/GC cycles and FET cycles as well as corticosteriods, antibiotics, and baby aspirin. ResultsTabled 1IVFDO/GCFETPREGNANT73/184(39.67%)30/38(78.95%)62/106(58.49%)NON-PREGNANT111/184(60.33%)8/38(21.05%)44/106(41.51%)LOSS23/73(31.50%)5/30(16.67%)24/62(38.70%) Open table in a new tab Evaluated by χ2 analysis. Evaluated by χ2 analysis. ConclusionBy evaluating the data by χ2 analysis the following is true: 1)It is clear that pregnancy rates are statistically better when the uterine environment is controlled p<0.001. 2) Loss rates are similar whether or not the uterine environment is controlled p=0.998. 3)The time is approaching where HRT controlled cycles may be considered to be the best choice for ET. By evaluating the data by χ2 analysis the following is true: 1)It is clear that pregnancy rates are statistically better when the uterine environment is controlled p<0.001. 2) Loss rates are similar whether or not the uterine environment is controlled p=0.998. 3)The time is approaching where HRT controlled cycles may be considered to be the best choice for ET.

Importance of endometrial thickness in frozen-thawed embryo transfer: difference between hormone replacement protocol and natural cycle protocol

Endometrial (EM) thickness is an important prognostic factor of fresh embryo transfer and its significance has been proven by many studies. However, only few studies have evaluated the relationship between endometrial thickness and cycle outcome in frozen-thawed embryo transfer (FET). The purpose of this study is to assess the values of EM thickness in hormone replacement(HRT) cycle FET and in natural cycle FET.

Corticosteroids regulate 5-HT 1A but not 5-HT 1B receptor mRNA in rat hippocampus

The role of mineralocorticoid and glucocorticoid receptors (MR and GR, respectively) in the regulation of serotonin receptors has not been clearly delineated. There is no consensus regarding the regulation of 5-HT 1A receptors, and corticosteroid regulation of 5-HT 1B mRNA has not been previously studied. We compared the effects of long-term (two week) adrenalectomy (no MR or GR activation) and several hormone replacement protocols designed to stimulate MR selectively (ALDO), MR and GR (HCT), and continuous MR with cyclical GR activation (SHAM adrenalectomy). 5-HT 1A and 5-HT 1B mRNAs were measured by in situ hybridization in hippocampus and raphe nuclei. None of the experimental manipulations altered 5-HT 1B mRNA levels in the hippocampus or dorsal raphe, and also had no effect on 5-HT 1A mRNA in dorsal or median raphe. However, 5-HT 1A mRNA levels were regulated in a complex manner in the different subfields of hippocampus. We conclude that both MR and GR play an integrated role in regulating 5-HT 1A mRNA levels in hippocampus while having no effect on 5-HT 1B mRNA levels under these conditions.

The effectiveness of sublingual progesterone administration during cryopreserved embryo transfer cycles: results of a matched follow-up study

To compare cryopreserved ET pregnancy rates in subjects receiving either sublingual parenteral P. Matched follow-up study. University-based assisted reproduction program. Women undergoing cryopreserved ET between January 1993, and December 1994. Cases received a hormone replacement protocol containing oral E2 and sublingual P and controls received a hormone replacement protocol containing oral E2 and parenteral P. Cases and controls were matched one-to-one according to age, number of embryos transferred, embryo grade, and route of ET. Cryopreserved embryos were thawed and transferred in all patients in an identical manner independent of the route of P administration. Clinical and ongoing pregnancy rates. Of 61 ET cycles performed in the sublingual P group, there were 16 clinical pregnancies (26.2%) and 12 ongoing pregnancies (19.7%). Of the 61 ET cycles in the parenteral P group, there were 14 clinical pregnancies (23.0%) and 11 ongoing pregnancies (18.0%). A chi 2 test revealed no significant differences in either clinical or ongoing pregnancy rates according to the route of P administration. This data suggests that sublingual P administration is an effective alternative to parenteral P administration in preparing the endometrium for the implantation of cryopreserved embryos.

Comparison of transdermal versus oral estradiol on endometrial receptivity

To compare the effects of oral micronized E2 with transdermal E2 on endometrial receptivity in women undergoing oocyte donation. Prospective, randomized, crossover trial. Serum E2 and P concentrations were measured on cycle days 14 and 22 (luteal day +8). Endometrial biopsies were obtained on day 22 and read in a blinded fashion for histology and beta-3-integrin expression. University-based donor oocyte program. Twenty-seven patients presenting for donor oocytes. Endometrial histology and beta-3-integrin expression. The endometrial glandular histology in women given oral micronized E2 was delayed by a mean of 1.6 days in comparison to that of women given transdermal E2. Seventy percent of women given oral E2 displayed a lag > or = 4 days whereas 29.6% given transdermal E2 displayed a similar lag. Serum E2 levels were 1,194 +/- 108.8 pg/mL (mean +/- SEM; conversion factor to SI unit, 3.671) in women on oral micronized E2 and 117.4 +/- 14.0 pg/mL in those on transdermal E2. The supraphysiologic serum E2 levels associated with oral micronized E2 may have a deleterious impact on endometrial receptivity. The development of more physiologic hormone replacement protocols may enhance endometrial receptivity and lead to improved clinical pregnancy rates.

Premature luteinization in controlled ovarian hyperstimulation has no adverse effect on oocyte and embryo quality

To determine if premature luteinization has an adverse effect on oocyte and, hence, embryo quality. Retrospective evaluation of anonymous ovum donors/oocyte recipients. A large oocyte donation program. Sixty-eight women undergoing controlled ovarian hyperstimulation (COH) as ovum donors were matched to 68 women with ovarian failure as ovum recipients who had endometrial maturation exogenously controlled by an identical hormone replacement protocol. Serum was collected for E2 and P in donors and recipients. The incidence of premature luteinization was determined in donors. Cycle characteristics were compared between donors with and without premature luteinization, with emphasis on oocyte and embryo quality. Implantation rates per embryo and delivery rates per transfer were measured in recipients. Twenty-one (31%) of the donors demonstrated premature luteinization. Serum P was higher on day before hCG, day of hCG, and day after hCG in women demonstrating premature luteinization. However, there were no differences between donor cycles with or without premature luteinization as determined by donor age, ampules of gonadotropins used, day of hCG administration, peak E2, total number of oocytes, and number of mature oocytes retrieved. Ovum recipients were of similar age and had similar E2 exposure (area under the E2 curve) before P administration. Similar fertilization rates, incidence of polyspermia, number of embryos transferred of similar embryo grade, and similar implantation rates and deliveries per transfer were observed in women receiving oocytes from donors with and without premature luteinization, respectively. Similar oocyte quality, fertilization, and polyspermia rates, embryo quality, implantation, and delivery rates suggest that any negative impact of premature luteinization on pregnancy rates in COH cycles from young women is not due to an adverse effect of PL on oocyte and hence embryo quality, but rather on the endometrial environment.

The effect of desogestrel for hormone replacement therapy on the blood lipid profiles of postmenopausal women

Objective: To determine the effect of a hormone replacement protocol containing conjugated equine estrogens and desogestrel (which has a highly selective progestogenic and low androgenic effect) as the progestogen, on the plasma lipid profile, as compared with two other hormone replacement treatments (HRT). Method: Eighty-nine healthy post-menopausal women were divided prospectively into four groups. A control group of 24 women did not receive HRT. Twenty-nine women received conjugated equine estrogen and medroxyprogesterone, and 13 women received a protocol containing estradiol, estriol and norethisterone acetate. Fasting blood lipid was taken at the end of each third cycle. The cumulative therapeutic response was calculated in each group as compared with initial values and between groups. Significance was analyzed by t-tests. Results: A protocol containing desogestrel significantly decreased low-density lipoprotein cholesterol (27%; P < 0.05) and increased high-density lipoprotein cholesterol (HDL-C) by 30% (P < 0.05%) after 9 months. The ratio of total cholesterol to HDL-C also decreased significantly (44%; P < 0.05). Conclusion: The most beneficial effect on plasma lipid profile was obtained with an HRT protocol containing desogestrel as the progesterone.

Effect of hyperglucagonemia on hepatic glycogenolysis and gluconeogenesis after a prolonged fast

The aim of this study was to determine if glucagon can stimulate hepatic glucose production in prolonged fasted (7 days) animals. Two protocols were used; in one ("hormone replacement"; n = 4), intraportal basal replacement amounts of insulin and glucagon were given during a somatostatin infusion, whereas, in the other ("glucagon excess"; n = 5) basal insulin was given along with somatostatin and excess glucagon. Plasma insulin levels were similar and constant throughout both protocols (6 +/- 1 microU/ml). The plasma glucagon was basal in the hormone-replacement protocol (49 +/- 9 pg/ml) but rose from 46 +/- 7 to 448 +/- 35 pg/ml (P less than 0.05) in the other protocol. Plasma glucose levels and the rates of glucose production were unchanged during hormone replacement but rose from 100 +/- 5 to 199 +/- 28 mg/dl and from 1.5 +/- 0.1 to a peak of 5.6 +/- 0.2 mg.kg-1.min-1 at 15 min (P less than 0.05) and an eventual plateau of 2.7 +/- 0.2 mg.kg-1.min-1 (P less than 0.05) in response to glucagon excess. Because of the sluggish increase in gluconeogenic parameters, the early marked rise in glucose production was attributable to increased glycogenolysis. Eventually, however, the gluconeogenic rate rose, with net hepatic uptake of alanine increasing 50% and fractional alanine extraction doubling. Gluconeogenic efficiency and conversion increased in response to glucagon excess by 0.30 +/- 0.05 and 159 +/- 48%, respectively, although it should be noted that these parameters rose 0.15 +/- 0.06 and 150 +/- 49% in the hormone-replacement protocol. In conclusion, even after a prolonged fast physiological glucagon can cause hyperglycemia.(ABSTRACT TRUNCATED AT 250 WORDS)