Preparation Of Endometrium Research Articles

P-735 Is Artificial Intelligence (AI) currently able to provide evidence-based scientific responses on methods that can improve the outcomes of embryo transfers?

Abstract Study question Could chatbots potentially be used as tools for both patients’ and physicians’ education in an infertility journey? Summary answer Artificial Intelligence (AI) is not yet in a position to give clear, evidence-based recommendations in the field of fertility, particularly concerning embryo transfer. What is known already The rapid development of AI has raised questions about its potential uses in different sectors of everyday life. Individuals from diverse fields have tried to incorporate its usage in their personal but also in their professional lives, with varying levels of success. Specifically in medicine, ChatGPT has been studied intensely with more than 400 related articles having been indexed in PubMed until May 2023, while AI has reportedly also succeeded in several standardized medical tests and passed several Medical Board examinations. Hence the question arises whether chatbots could be used as tools for clinical decision-making or patients’ and physicians’ education. Study design, size, duration We used nine of the most popular free AI chatbots available (ChatGPT, Bard, Writesonic, You, Perplexity, Learnt, Bing, Magickpen, and Rytr) and entered the following command: “Write me a 300-word scientific essay about evidence-based methods that can improve the outcomes of embryo transfer” in May 2023. We collected the responses and extracted the methods each chatbot suggested. When sufficient similarity among answers was present we categorized the answers under one category to facilitate the study. Participants/materials, setting, methods We calculated descriptive statistics and the prevalence of each response. We used as a comparator for widely acceptable practices that are proven to improve embryo transfer outcomes the 2017 ASRM guideline on performing embryo transfer taking also into consideration more current literature. Data was compared using chi-squared tests and a level of p < 0.05 was used as the threshold of statistical significance. Main results and the role of chance The range of the recommendations was from one to nine per chatbot (median = 4, IQR = 2) with an average of 4.78 suggestions per chatbot. Out of a total of 43 recommendations, which could be grouped into 19 similar categories, only 3/19 (15.8%) were evidence-based practices, those being “ultrasound-guided embryo transfer”, which was also the most commonly appearing response, appearing in 7/9 (77.8%) chatbots, “single embryo transfer” appearing in 4/9 (44.4%) chatbots and “use of a soft catheter” in 2/9 (22.2%) chatbots. Some controversial responses appeared even more often than the two latter evidence-based ones with “preimplantation genetic testing (PGT)” being the second most common response with 6/9 chatbots suggesting it (66.7%) and the vague suggestion of “optimal endometrium preparation” being in the third place with 5/9 chatbots (55.6%), both non-evidence-based practices to improve embryo transfer. The majority of the recommendations were unique, with 10 answers appearing only once (1/9; 11.1%), those being “endometrial scratching”, “natural cycle embryo transfer”, “use of GnRH antagonist protocol”, “blastocyst transfer”, “use of specialized catheter”, “preimplantation genetic screening (PGS)”, “mock embryo transfer”, “uninterrupted embryo culture”, “minimizing transfer time”, and “maintaining temperature and pH of the culture media”. Limitations, reasons for caution Firstly, we only used some of the most popular chatbots and not all existing ones. Additionally, chatbots tend to give different answers when repeatedly asked the same questions. However, we believe that our study effectively captures the prevailing practices of chatbot users, who typically pose a question only once. Wider implications of the findings Both patients and physicians should be wary of guiding care based on chatbot recommendations in infertility since the majority of responses consists of scientifically unsupported recommendations. Chatbot results might improve with time especially if trained to obtain information from validated medical databases, however, this will have to be verified scientifically. Trial registration number N/A

The use of oral nomegestrol acetate/estradiol in rapid and random start preparation of endometrium before office hysteroscopic polypectomies: A multicenter, prospective, randomized controlled trial

ObjectiveTo evaluate the use of oral nomegestrol acetate/estradiol in random start rapid preparation of endometrium before office hysteroscopic polypectomy. Study designMulticenter, prospective, randomized controlled trial. SettingUniversity hospitals. Participants80 adult women undergoing office hysteroscopic polypectomy between January 2023 and March 2024 were randomized to intervention (n = 40) or control (n = 40). Exclusion criteria included the presence of endouterine pathology other than endometrial polyps solely. MethodsSubjects in the intervention group were treated with oral nomegestrol acetate/estradiol 1.5 mg/2.5 mg/day started taking the drug from an indefinite time in the menstrual cycle (random start) for 14 days. Subjects in the control group did not receive any pharmaceutical treatment and underwent polypectomy between days 8 and 11 of the menstrual cycle. ResultsOn the day of the procedure, the difference in pre- and post-office hysteroscopic polypectomy endometrial ultrasound thickness was statistically significant between the two groups, with endometrial thickness in both measurements being thinner for the intervention group (p < 0.001). In the nomegestrol acetate/estradiol-treated group, compared with the control, there was also a statistically significant difference in the physician’s assessment of the quality of endometrial preparation (p < 0.001), the quality of visualization of the uterine cavity (p < 0.001), and satisfaction with the performance of the procedure (p < 0.001). Finally, all surgical outcomes analyzed were better in the treatment group. ConclusionTreatment with nomegestrol acetate/estradiol could provide rapid, satisfactory and low-cost preparation of the endometrium before office polypectomy, thus improving surgical performance and woman’s compliance. Trial registrationClinicalTrials.gov NCT06316219.

#144 : Randomized Controlled Trial Evaluating Efficacy of Autologous Platelet-Rich Plasma Therapy for Patients with Recurrent Implantation Failure in Frozen-Thawed Embryo Transfer After PGT-A

Background and Aims: Despite keen development of ART, recurrent implantation failure (RIF) remains a challenging dilemma for fertility specialists. As it contains significant growth factors involved in delicate process of implantation, platelet–rich plasma (PRP) therapy should promote endometrial receptivity and improve ART. Objective: To evaluate if the intrauterine perfusion with autologous PRP enhances frozen-thawed embryo transfer effectiveness in patients with RIF after PGT-A. Methods: Study type: Interventional. Design: randomized controlled study Intervention Model: Parallel Assignment Masking: open label After obtaining institutional review board approval, 232 women aged 28-42 years were involved. Matching criteria: RIF, normal karyotype, absence of uterine factors of infertility, availability of euploid embryos after PGT-A (NGS). 2 groups of patients: study group (N = 118): single IP with 2.0 ml of autologous PRP on day 10-11 of menstrual cycle; Control group: no therapy (N = 114). Endometrium preparation was carried out according to standardized protocol. Primary outcome measure was clinical pregnancy rate. Secondary outcome measures were pregnancy loss rate, endometrial thickness and adverse event. Results: The clinical pregnancy rate was higher in the study group (63.55% vs 38.59%) ([Formula: see text]2=14.462, OR=2.775, 95% CI 1.630 - 4.722, p&lt;0,001). The endometrium thickness before intervention didn’t between groups (7.3 vs 7.4 mm), however, endometrium thickness measured just before embryo transfer was significantly higher in the study group (10.5 vs 8.4 mm, Student’s t-test value: 11.87; number of degrees of freedom f=230; Critical value of Student’s t-test=1.972, at significance level [Formula: see text]= 0.05). The pregnancy rate loss did not differ between groups ([Formula: see text]2=0.033, OR=0.908, 95% CI 0.324 – 2.546, p&gt;0,05). No adverse event was noted. Conclusions : – The PRP intrauterine perfusion should be considered perspective, safe and cost-effective therapy method for patients with RIF. – PRP does not influence on pregnancy loss rate – Meta-analysis is required. Support: None

Live birth rate following endometrial preparation with daily versus depot GnRH agonist

Background Gonadotrophin-releasing hormone agonist (GnRHa) downregulates gonadotropin secretion in the pituitary gland. It is used both in ovulation induction protocols and in artificial endometrium preparation. Frozen—thawed embryo transfer to artificially prepared endometrium (FET-APE) is a frequent procedure in vitro fertilization (IVF) which requires GnRHa. It can be used either as a daily low-dose injection or as a single depot injection. It is unclear which of these two regimens is superior for artificial endometrium preparation. Methods We evaluated the data of 72 patients who had undergone frozen embryo transfer following the 5th day Preimplantation Genetic Test-aneuploidy (PGT-A) between 2018–2021. All embryos were genetically screened, and euploid single embryos were transferred. Group 1 (n: 36) used depot GnRHa, and Group 2 (n: 36) used single daily injections for artificial endometrial preparation. The outcomes for Beta Human Chorionic Gonadotrophin (BHCG) positivity and live birth rates (LBR) was compared. Results The BHCG positivity for Group 1 and Group 2 was 75% and 80.6%, respectively. The LBR for Group 1 and Group 2 were found to be 58.3% and 63.9%, respectively. There was no statistically significant differences between the two groups. Conclusions In artificial endometrium preparation, depot GnRHa offers cheaper and more convenient alternative to single daily dose injections, particularly in busy clinical settings.

Initiating luteal phase support with sc progesterone based on low serum progesterone on the transfer day in true natural cycle frozen embryo transfers.

Concerning contemporary in-vitro fertilisation (IVF) practice, the use of frozen embryo transfer (FET) cycles has become more common than fresh transfers. Natural cycle (NC), programmed artificial cycle and mild stimulation cycle are primary endometrium preparation cycles. Monitoring serum progesterone levels in FET cycles are in the scope of current research focus. Low progesterone levels on the day of embryo transfer is presumed to negatively affect pregnancy outcomes, while progesterone supplementation may improve pregnancy rates. The purpose of our trial is to evaluate whether initiating subcutaneous (SC) progesterone supplementation on the day of embryo transfer when serum progesterone levels are below 10 ng/mL in tNC-FET will result in pregnancy rates comparable to those of patients with sufficient serum progesterone. Retrospective single centre study was conducted between August 2022 and April 2023 with 181 tNC-FETs. Patients were separated into groups according to serum progesterone concentrations (≥10 ng/mL and <10 ng/mL) on embryo transfer (ET) day. S.c progesterone (25 mg) was given on the day of ET when serum progesterone was <10 ng/mL, continuing until the 10th gestational week. Blood samples for pregnancy tests were collected 12 days after ET. Outcome parameters were pregnancy rate, clinical pregnancy rate (CPR), miscarriage rate, multiple pregnancy rate, biochemical pregnancy, and ongoing pregnancy rate (OPR). About half (49.7%) had adequate progesterone concentrations (≥10ng/mL) on ET day. There was no significant difference between the groups regarding positive pregnancy test, OPR, multiple pregnancies, and miscarriage rates (57.8% versus 52.7%; 34.4% versus 29.7%, 1.1% versus 2.2%; 7.8% versus 5.5%; respectively, for progesterone concentrations on ET day ≥10 ng/mL and <10 ng/mL). With 55.2% of transfers leading to clinical pregnancy, significant differences emerged in biochemical pregnancy and CPR (3.3% vs 12.1%, P=0.02; 54.4% vs 40.7%, P=0.03, for ≥10 ng/mL and <10 ng/mL progesterone concentrations on ET day). This study indicates that nearly half of the tNC-FETs may need luteal phase support due to low progesterone. However, 25 mc sc progesterone rescued the luteal support and yielded similar OPR as compared to normal progesterone group. Further studies are needed for understanding optimal progesterone levels, supplementation effectiveness, and potential benefits of earlier supplementation in FETs.

Letrozole During Frozen Embryo Transfer in Women With Polycystic Ovarian Syndrome: A Randomized Controlled Trial.

To compare live-birth rates between letrozole application and artificial cycle for endometrium preparation during frozen embryo transfer (FET) cycle among women with polycystic ovarian syndrome (PCOS). A randomized controlled trial was conducted. Women with PCOS were randomized to letrozole application for ovulation induction compared with artificial cycle for endometrial preparation during FET. The primary outcome was live-birth rate per embryo transfer. Secondary outcomes included pregnancy-related outcomes, perinatal outcomes, and maternal complication rates. Assuming α=0.05 and 80% power, 186 patients per group were required to demonstrate a difference of 15% in live-birth rate: 205 patients (at least) per group were randomized to allow for a 10% dropout rate. Four hundred twenty patients were enrolled from 2018 to 2021. Two hundred ten patients were assigned to the letrozole application group, and 210 were assigned to the artificial cycle group. There was no difference in the live-birth rate (42.4% vs 42.9%, P =>.99). There was no difference in secondary outcomes, including clinical pregnancy rate (51.4% vs 56.2%, P =.378), implantation rate (51.8% vs 55.8%, P =.401), and miscarriage rate (8.6% vs 11.0%, P =.511). For perinatal outcomes, singleton birth weight was significantly higher in the artificial cycle group (3,108±56 g vs 3,301±58, P =.018), and the incidence of gestational diabetes mellitus (GDM) was significantly higher in letrozole application group (14.6% vs 5.6%, P =.050). The other outcome was no difference in maternal complications. There was no difference in pregnancy outcomes between letrozole application compared with artificial cycle for endometrial preparation in women with PCOS who underwent FET. The risk of GDM was higher in the letrozole application group, and the singleton birth weight was lower in the artificial cycle group. Chinese Clinical Trial Registry, ChiCTR1800014746.

Hyperbaric oxygen therapy: a possible choice for patients with resistant thin endometrium during frozen embryo transfer treatments

BackgroundThin endometrium is considered suboptimal for embryo implantation, leading to compromised pregnancy rates without effective therapies. While some studies have reported promoted endometrial growth after a period of hyperbaric oxygen therapy (HBOT) in patients with intrauterine adhesion, there have been no reports in patients with resistant thin endometrium. The purpose of this study was to investigate the impact of HBOT on endometrium growth and pregnancy outcomes in patients with resistant thin endometrium during frozen embryo transfer (FET) treatments.MethodsThis prospective pre-post cohort study was conducted at a university-affiliated assisted reproductive medical center between October 2021 and December 2022. Patients who had experienced at least one canceled transfer cycle due to a thin endometrium(< 7 mm) on the endometrium transformation day, despite the use of standard therapies as well as adjuvant therapies, were enrolled in the study. Patients were assigned voluntarily to either the HBOT group or the concurrent control group. The HBOT group received daily HBOT for at least 10 days during the proliferative phase, in addition to the routine endometrium preparation methods and the concurrent control group underwent cycles without HBOT. Propensity score matching (PSM) was used to ensure comparability between the groups. Both self-control and case-control comparisons were conducted. The primary outcome measured was endometrial thickness (ET) on the day of endometrium transformation. Secondary outcomes included intrauterine pregnancy rate (IPR), embryo implantation rate (IR), miscarriage rate, and others.ResultsPatients in the HBOT group demonstrated a significantly thicker endometrial thickness on the day of endometrium transformation after undergoing therapy (5.76 ± 1.66 vs. 6.57 ± 1.23, P = 0.002). This improvement was accompanied by a decreased rate of cycle cancellations. Baseline parameters and endometrial thickness were comparable between the HBOT group and the concurrent control group during the cycle. The IPR was similar in patients who received cleavage-stage embryos (0.0% vs. 6.7%, P = 1.00), but significantly higher in patients in the HBOT group who received blastocysts (53.8% vs. 18.2%, P = 0.017).ConclusionsA period of HBOT prior to endometrium transformation contributes to increased endometrial thickness and facilitates blastocyst implantation in patients with resistant thin endometrium during FET treatments.Trial registrationThe trial was registered on the Chinese Clinical Trial Registry (registration no. ChiCTR2300072831, retrospectively registered).

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.

Full-term live birth in a woman with 17α-hydroxylase and 17,20-lyase deficiency with assisted reproductive technology: a case report

Background17α-hydroxylase deficiency, which is caused by a CYP17A1 gene mutation, is a rare type of congenital adrenocortical hyperplasia that mainly manifests as hypertension, hypokalaemia and sexual dysplasia. To date, few pregnancies associated with this syndrome have been reported.Case presentationWe describe a 35-year-old Chinese woman with nonclassical congenital adrenal hyperplasia (NCCAH) due to 17α-hydroxylase/17,20-lyase deficiency who achieved pregnancy after in vitro fertilization (IVF) and frozen-thawed embryo transfer. She had secondary amenorrhea since she was 27, and subsequently, high level of progesterone in the follicular phase was found during a blood test. A compound heterozygous mutation was found in the CYP17A1 gene, c.1263G > A and c.985_987delinsAA. The patient was given standardized treatment with dexamethasone. Due to ovulation disorder, IVF was performed. She underwent whole embryo vitrification freezing. Frozen-thawed embryo transplantation was performed following the artificial cycle protocol of endometrium preparation, resulting in a singleton pregnancy. At 39 weeks and 1 day of gestation, caesarean section was performed due to the breech position of the foetus.ConclusionA high level of progesterone reduces endometrial receptivity. Standardized treatment with dexamethasone and frozen-thawed embryo transfer with an artificial cycle protocol of endometrium preparation should be the choice for infertile female patients with CYP17A1 deficiency.

P-548 Randomized controlled trial evaluating efficacy of autologous platelet –rich plasma therapy for patients with recurrent implantation failure in frozen-thawed embryo transfer after PGT-A

Abstract Study question To evaluate if the intrauterine perfusion with autologous PRP enhances frozen-thawed embryo transfer effectiveness in patients with recurrent implantation failure (RIF) after PGT-A. Summary answer The intrauterine perfusion (IP) with autologous PRP should be considered perspective, effective and safe therapeutic tool for patients with RIF What is known already Despite keen development of embryology, routine implementation of preimplantation genetic testing and assessment of endometrial receptivity, recurrent implantation failure (RIF) remains a challenging dilemma for fertility specialists. As it contains significant growth factors involved in delicate process of implantation, platelet –rich plasma (PRP) therapy should promote endometrial receptivity and improve assisted reproductive technology outcomes. Moreover, being autologous, PRP is not expected to trigger adverse immune event in the patient and is therefore perceived to be therapeutically safe. Pilot study conclusions have been inspiring however there is strong need for randomized controlled trials. Study design, size, duration Study type: Interventional. Study design: randomized controlled study Intervention Model: Parallel Assignment Masking: open-label Study size: 232 Duration: 40 months (July, 2019 - October, 2022) Multicenter trial: 3 ART clinics After obtaining institutional review board approval, 232 women aged 28 - 42 years were involved. Matching criteria: RIF, normal karyotype, absence of uterine factors of infertility, availability of euploid embryos after PGT-A Participants/materials, setting, methods 2 groups of patients: study group (N = 118): single intrauterine perfusion with 2.0 ml of PRP on day 10 -11 of menstrual cycle; Control group (N = 114): no therapy. Endometrium preparation was executed according to standardized protocol of hormone replacement therapy. PRP preparation was carried using patented tubes. In all cases SET was performed. Primary outcome measure was clinical pregnancy rate. Secondary outcome measures were pregnancy loss rate, endometrial thickness and adverse event. Main results and the role of chance The clinical pregnancy rate was higher in the study group (63.55% vs 38.59%) (χ2=14.462, OR = 2.775, 95% CI 1.630 - 4.722, p &amp;lt; 0,001). The endometrium thickness before intervention didn’t between groups (7.3 vs 7.4 mm), however, endometrium thickness measured just before embryo transfer was significantly higher in the study group (10.5 vs 8.4 mm, Student’s t-test value: 11.87; number of degrees of freedom f = 230; Critical value of Student’s t-test=1.972, at significance level α = 0.05). The pregnancy rate loss did not differ between groups (χ2=0.033, OR = 0.908, 95% CI 0.324 – 2.546, p &amp;gt; 0,05). No adverse event was noted. Limitations, reasons for caution The number of recruited participants was limited. Nevertheless, these data show statistically significant positive effect on ART outcomes. Further investigation and meta-analysis are required. Wider implications of the findings According to obtained results intrauterine perfusion with PRP should be recommended in FET cycles in patients with RIF. Given proven promotion effect on endometrial thickness the intrauterine perfusion (IP) with autologous PRP should be considered perspective and safe management method for patients with thin endometrium. Trial registration number 4765

P-475 Effect of transdermal estradiol on endometrial preparation in frozen-thawed embryo transfer: A randomized control study.

Abstract Study question Is patient usage of transdermal estradiol more effective than oral estradiol on endometrial preparation in frozen-thawed embryo transfer cycles? Summary answer This study showed no significant differences in clinical pregnancy rates between the 2 groups. Transdermal gel have advantage of better patient comfort, lesser side effects. What is known already Estrogen and progesterone are crucial factors for endometrial preparation in frozen embryo transfer (FET) cycles. Studies assessing different forms of estradiol in FET have already been published. However, literature and studies in Vietnam are still limited to evaluating, research evaluating transdermal estrogen in ART. This study aimed to evaluate the use of transdermal estradiol gel and compare it with oral estradiol for the endometrium preparation in frozen-thawed embryo transfer (FET) cycles. Study design, size, duration This randomized clinical trial (RCT) included 380 frozen embryo transfer (FET) cycles from February 2020 to August 2021 at the IVF Department, Hung Vuong Hospital. Participants/materials, setting, methods They were randomized into one of the two groups. Group A (n = 190) received oral estradiol and group B (n = 190) received estradiol gel. In both groups, medication was started on day 2 of the menstrual, and endometrial thickness was monitored by ultrasound. Main outcomes were the following: serum estradiol level , endometrial thickness,.... Secondary outcomes were CPR, MR, and side effects in the 2 groups. Statistical testing was performed with Stata 14. Main results and the role of chance There was a significant difference in estradiol level on the day of progesterone administration and embryo transfer between the two groups (270.5 pg/ml versus 186.5 pg/ml, p, p. &amp;lt;0.001). According to the comparison, the two groups were not significantly different in the endometrial thickness on the day of progesterone administration (p = 0.85). as the data suggest, the total dose of estradiol used and the total number of days of dosing were similar in the two groups. The biochemical and clinical pregnancy rates were similar between the two groups and did not a significantly differ (56.2% vs. 52.2%, p = 0.474). The rate of miscarriage was higher than in the study group, but it was not statistically significant. Almost 20.3% of patients (n = 37) in group A had mild adverse effects when compared with only 10.1% (n = 18) in group B, and this was clinically significant (P = 0.007). Limitations, reasons for caution The limitation of our study was not asses ongoing pregnancy rate and live-birth rate. Wider implications of the findings Patients who estradiol valerate is contraindicated such as, high risk for deep vein thrombosis, hyperlipidemia, and clotting disturbance we can use oestrogel to be safe. It is suggested that estradiol transdermal patches be used instead of oral estradiol in FET cycles Trial registration number ISRCTN15301227

O-021 The dose of micronised vaginal progesterone prior to frozen embryo transfer in artificially prepared cycles: the more the better?

Abstract Study question Does a higher daily dose of micronized vaginal progesterone (MVP) increase live birth rates (LBR) or diminishes risk of early pregnancy loss (EPL)? Summary answer An increased dose of MVP does not affect reproductive outcomes. What is known already Endometrial preparation in frozen embryo transfer (FET) cycles can be achieved either in a natural cycle (NC), a stimulated cycle or an artificial cycle (AC). Despite growing advocacy for utilization of NC for FET mainly because of pregnancy complications, there are still numerous indications and strengths of AC, such as convenient monitoring and planning. In AC-FET cycles exogenous estradiol (E2) and progesterone (P) are administered consecutively in order to mimic a natural cycle. Although MVP still being the most widely used medication for LPS in AC-FET cycles, dose finding studies are lacking. Study design, size, duration This is a retrospective study performed at a university-affiliated centre including patients performing a single blastocyst transfer from January 2016 till June 2021. Pregnancy outcomes were compared between patients receiving 600mg (3x200mg) or 800mg (2x200mg) of MPV in the second phase of an AC-FET cycle. The time period was chosen to incorporate the empiric change made in the inner guidelines regarding artificial cycles LPS in autumn 2018. Participants/materials, setting, methods Patients aged 19-39, who underwent the first frozen single blastocyst transfer were included. Only HRT cycles, where after exogenous estradiol endometrium preparation LPS was started with MVP 600mg or 800mg were included. Patients lost to follow-up, with missing data, with known uterine pathology, recurrent miscarriages, with switch to MNC, with more than one progesterone route planned or modified LPS were excluded. Main results and the role of chance 1825 artificial cycles for FET were included. 827 supplemented with 600mg of MVP -MVP600 group and 998 with 800mg of MVP – MVP800 group. The MVP600 and MVP800 groups did not differ in BMI 24.02 (SD 4.73) vs 23.81 (SD 4.6) (p = 0.37), rank of embryo transfer 1.93 (SD 1.41) vs 1.77 (SD1.19) (p = 0.11), or the thickness of the endometrium at planning 8.67mm (SD1.79) vs 8.51mm (SD 1.7) (p = 0.06). Yet, MVP 800mg group was slightly older than MVP600 group 31.99 (SD 3.72) vs 30.84 (SD 3.9) (p &amp;lt; 0.001). Positive hCG was 58.65% (485 out of 827) for MVP600 and in 62.12% (620 out of 998) for MVP800 group (p = 0.13). LBR per positive hCG 64.18% (292 out of 455) in MVP600 and 67.17% (397 out of 591) in MVP800 group (p = 0.31). Early pregnancy loss per positive hCG did not differ between the groups, and including biochemical losses, was 32.75% in MVP600 (149 out of 455) vs 30.8% in MVP800 (182 out of 591) (p = 0.5). Multivariable regression analysis adjusting for relevant confounders (eg. BMI, endometrium thickness) revealed that the dose of MVP 600mg vs 800mg is not significantly associated with EPL OR 0.92 (95% CI 0.71-1.22) p &amp;gt; 0.592. Limitations, reasons for caution The main limitation is the retrospective design of our study, with an inherent risk of bias. Furthermore, we could not compare the blood progesterone values at the day of the transfer as in MVP600 they were not routinely performed, so the need for additional LPS could not be compared. Wider implications of the findings This is the largest study dose finding study comparing the two progesterone administration doses. The higher dose of MVP does not improve reproductive outcomes, but might be more convenient due to a twice daily application. Trial registration number BUN: 1432022000074 EC number: EC-2022-102

Programmed frozen embryo transfer cycles are associated with a higher risk of abnormal placental development: a retrospective cohort study of singleton live births.

Abnormal placental development can lead to adverse outcomes for both mother and fetus. The effect of different types of endometrium preparation regimens of frozen-thawed cycles on the placental development features associated with the perinatal outcomes remains unclear. Hence, we conducted a retrospective cohort study to assess the impact of specific endometrial preparation regimens on placenta-mediated pregnancy complications in singleton live births. A retrospective cohort study was conducted evaluating data of all singleton live births both conceived naturally or by in vitro fertilization (IVF) therapy from 2018 to 2020 at our hospital. Two exposed groups of frozen-thawed embryo transfer (FET) were created by the endometrium preparation regimen as the modified natural cycles (mNC) and the programmed cycles. The nonexposed group was the singleton pregnancies conceived naturally. The obstetrical and perinatal outcomes were compared among the three groups using multivariate analysis to adjust the results for determinants potentially associated with the abnormal placental development. A total of 2186 pregnant women with singleton live births were included in our final analysis and were divided into three groups as naturally conceived group (n=1334), mNC-FETs group (n=217) and programmed-FETs group(n=635). After adjusting for maternal age and parity, no significant difference was observed on the risk of placental disorders between mNC-FET cycles and natural conceived pregnancies (aOR 1.16; 95%CI 1.31-7.01), while programmed-FET cycles were associated with a higher occurrence of placental disorders (aOR 5.36; 95%CI 3.63-8.05). Using the mNC-FET group as a reference and adjusting for confounders such as maternal age, parity, endometrial thickness, and number of embryos transferred, we found that the main manifestation of abnormal placentation in programmed FET cycles was abnormal placental attachment, including placental adhesion and placenta increta (aOR 2.50, 95%CI 1.36-4.90). The dysfunction of placentation in programmed-FET cycles was independently associated with the type of infertility, the total dose of Femostone and thinner endometrium. Additionally, placental disorders in the programmed-FET group were associated with higher rate of preeclampsia, postpartum hemorrhage and Cesarean section. Our retrospective study revealed that the programmed-FET has a substantial impact on placental development, resulting in a higher incidence of preeclampsia, postpartum hemorrhage and Cesarean section. These findings have significant implications on clinical decision-making.

A pilot study of the intrauterine non-ablative erbium laser effectiveness in the endometrium preparation for cryopreserved embryo transfer in women with a history of implantation failures

Background. Embryo implantation failure remains an urgent issue of assisted reproductive technologies (ART).&#x0D; Aim. To determine the effect of intrauterine irradiation with a non-ablative erbium laser on the endometrium state using the histological and immunohistochemical examination and to evaluate its effectiveness in ART cryo-protocols.&#x0D; Materials and methods. The study enrolled 25 women aged 2645 with 1 to 5 failed implantations who were planning a pregnancy in a cryopreserved embryo transfer protocol. On days 610 of the menstrual cycle, all patients underwent a single procedure of intrauterine irradiation of the endometrium and cervical canal mucosa with an erbium laser in a non-ablative mode using Fotona SP Dynamis laser system (Slovenia). The histological and immunohistochemical data of the endometrium before and 12 months after the procedure and the pregnancy rate with subsequent transfer of the cryopreserved embryo were assessed.&#x0D; Results. Intrauterine irradiation with a non-ablative erbium laser increased the proliferative activity of the endometrium (p=0.029), the expression of vascular endothelial growth factor (p=0.029), reduced the sclerosis lesions in the spiral arteries and endometrial stroma, increased the expression of progesterone and estrogen receptors, thus significantly increasing the effectiveness of the ART cryo-protocols (p=0.013).

Effectiveness of growth hormone in promoting endometrial growth in patients with endometrial dysplasia in frozen embryo transfer.

This study was designed to investigate the effect of growth hormone (GH) in promoting endometrial thickness, blood flow, and pregnancy outcome in patients with thin endometrium for frozen embryo transfer. Thirty-eight patients were recruited in the reproductive center of Jingzhou Hospital affiliated to Yangtze University who cancelled fresh embryo transfer due to thin endometrium and planned to undergo frozen-thawed embryo transfer (FET) from May 2019 to May 2020. The patients were randomly divided into the GH injection group (19 cases, endometrium preparation with hormone replacement therapy (HRT) and GH by subcutaneous injection) and the control group (19 cases, endometrium preparation with HRT). Both groups were similar in socio-demographic characteristics. After treatment, the thickness and volume of endometrium in the HRT & GH group were significantly increased (p < 0.05), and the growth rate was significantly higher than that in the control group (p < 0.05). The proportion of type A & B endometrium increased from 78.9% to 94.7% in the HRT & GH group. Moreover, the proportion of type Ⅰ and Ⅱ of endometrial blood perfusion in the HRT & GH group significantly increased compared with that before treatment. The human chorionic gonadotropin (hCG) positive rate (47.4 vs. 42.1%) and clinical pregnancy rate (36.8% vs. 31.6%) were slightly higher in the HRT&GH group than that in the control group. In conclusion, for patients with thin endometrium, HRT combined with subcutaneous injection of GH can increase the thickness and volume of the endometrium, improving the blood perfusion of the endometrium. This may play a positive role in improving endometrial receptivity and pregnancy outcome.

Effect of intramuscular injection of human chorionic gonadotropin on endometrium preparation in frozen-thawed embryo transfer cycle: A randomized clinical trial.

Assisted reproductive therapy (ART) has been developed remarkably in these decades; however, the rate of unsuccessful embryo implantation especially in the frozen-thawed embryo transfer (FET) cycles remains high and is reported up to 70%. The current study was designed to compare the effect of intramuscular injection of hCG on endometrium preparation and embryo implantation, in women undergoing FET compared to the control group. This clinical trial was done on 140 infertile women that underwent FET. The study sample was randomly allocated to the intervention group (two 5000 unit ampoules of hCG were injected intramuscularly before the first dose of progesterone administration) and the control group (without hCG injection). In both groups, 4 days after progesterone administration, the cleavage stage embryos were transferred. The study outcomes were biochemical pregnancy, clinical pregnancy and abortion rate. The average age of intervention and control group was 32.65±6.05 and 33.11±5.36 years, respectively. The basic information between two study groups did not differ significantly. The chemical (30% vs. 17.1%, P=0.073, relative risk (RR)=0.57) and clinical (28.6% vs. 14.3%, P=0.039, RR=0.50) pregnancy rates were higher in the intervention group compared to the control group; these higher ratios were only significant in clinical pregnancy rate. Abortion rate was not significantly (P=0.620) different between the intervention and control groups (4.3% vs. 1.4%, respectively). This study showed that intramuscular injection of 10000 IU hCG before the endometrial secretory transformation phase in cleavage-stage embryo, improves IVF cycle outcomes.

Infertility treatment for Chinese women with P450 oxidoreductase deficiency: Prospect on clinical management from IVF to FET.

Cytochrome P450 oxidoreductase deficiency (PORD) is a rare recessive disease with multiple clinical manifestations, which is usually diagnosed in neonates and children because of ambiguous genitalia or skeletal malformations. Moreover, the paucity of studies does not allow us to establish whether adult-onset PORD is associated with infertility. Here, we report clinical and laboratory findings in two phenotypically normal women diagnosed with PORD who underwent in vitro fertilization (IVF) and frozen embryo transfer (FET). We modified the gonadotropin stimulation protocol during controlled ovarian hyperstimulation (COH) and suggest the use of the vaginal 17β-estradiol route for endometrium preparation in hormone replacement therapy (HRT) cycles. We presume that PORD may be associated with infertility in several aspects, including disordered steroidogenesis, endometrium impairment, attenuation of drug metabolism, and the high risk of miscarriage. Our observations will help the early diagnosis and make a tailored approach to infertility management in adult-onset PORD.

Re-evaluation of mouse models of endometriosis for pathological and immunological research.

Endometriosis is an estrogen-dependent gynecological disease with chronic pelvic inflammation. In order to study the pathophysiology of endometriosis and examine the therapeutic effects of new pharmaceuticals for endometriosis treatment, different animal models had been developed in the last two decades, especially mouse models. However, no study evaluated the effects of various modeling approaches on pathology and immunology in endometriosis. This study aimed to compare endometriotic lesion development and immune profiles under different methods of establishing endometriosis models in mice, including estrus synchronization (ovariectomy with estrogen supplement versus male urine-soaked transfer bedding), endometrium preparations (whole uterus including endometrium and myometrium fragments versus solely endometrium fragments), and surgical transplantation (subcutaneous transplantation versus intraperitoneal injection). Our results showed that lesion growth under estrus synchronization by ovariectomy with estrogen supplement had a higher success rate and more proliferative endometrium, apart from higher body weight gain. Immune responses in peripheral blood were similar in the whole uterus and solely endometrium fragments and in intraperitoneal injection and subcutaneous transplantation, but a more innate immune response in the peritoneal microenvironment was found in solely endometrium fragments and intraperitoneal injection than counterparts. In conclusion, different endometriosis modeling methods result in different pathological and immunological features. Ovariectomy with estrogen supplement, solely endometrium fragments, and intraperitoneal injection are more suitable for both pathological and immunological studies of endometriosis in mice, which are important for mechanistic studies and immunotherapy development.

Is Frozen Embryo Transfer the New Norm in IVF?

Frozen embryo transfer is an established, highly successful technology in Assisted Reproductive Technologies. Its use as a part of a freeze only strategy is associated with a higher probability of live birth in high responders and a decrease incidence of ovarian hyperstimulation syndrome (OHSS). Its use in normal responders, maintains the probability of live birth compared to fresh embryo transfer and decreases the incidence of OHSS. Obstetric n neonatal outcomes in frozen as compared to fresh embryo transfer cycles are characterized by a decreased incidence of monozygotic twinning, of ectopic pregnancy, of small for gestational age babies, of premature labour, of antepartum hemorrhage and of perinatal mortality. On the other hand, an increased incidence of pregnancy induced hypertension, has been observed in frozen as compared to fresh embryo transfer cycles. This, however, appears to be associated with the absence of corpus luteum during endometrium preparation for embryo transfer, as is the case in frozen embryo transfer cycles using hormonal replacement. Overall, the increased efficacy and a safety present, if fresh embryo transfer following ovarian stimulation is avoided, redefine what should be the norm in modern in-vitro fertilization practice.

P-578 Oral, Vaginal or Intramuscular Progesterone in Programmed Frozen Embryo Transfer Cyles: A Pilot RCT

Abstract Study question What should be the optimal luteal phase support in programmed frozen embryo transfer (FET) cycles using vitrified-thawed blastocysts? Summary answer 40mg/day oral dydrogesterone, 180mg/day progesterone (P) vaginal gel and 100mg/day im P in oil revealed similar reproductive outcomes in programmed FET cycles. What is known already Luteal phase should be supported either in fresh (Yanushpolsky et al, 2015) or in FET cycles (Pabuccu et al, 2020). Endometrium preparation in FET cycles is outmost important for successful implantation. For this purpose, natural or programmed protocols have been suggested. In programmed FET cycles, exogenous P replacement is of critical importance, as estrogen use will inhibit ovulation and corpus luteum formation.Higher serum P level was associated with increased rates of ongoing pregnancy or live birth in programmed FET cycles (Melo et al 2021). Therefore, lack of a corpus luteum justifies precise and adequate luteal support. Study design, size, duration This was a randomized, parallel, phase IV-pilot RCT (NCT03948022), comparing 3 different luteal support options in programmed FET cycles. A total of 168 women aged between 20-40 years and having available blastocyst(s) were eligible for the study between April-December 2020. After excluding cases, 163 patients were randomly assigned to one of the P arms based on a computer- generated list to administer: 1-oral dydrogesterone 40mg/day (DYD) 2-vaginal %8 P gel 180mg/day (VAG) 3-im 100mg/day P (IM) Participants/materials, setting, methods Estradiol 2 mg TID was started on day 2 or 3 of menstruation for at least 7 days. On day 8, endometrial thickness was assessed. When it was &amp;gt;8 mm, each patient was randomly assigned to one of the intervention arms. After 5 days of P administration, ET was performed on the 6th day preceding serum P measurement. Primary outcome was ongoing pregnancy rate defined as viable healthy pregnancy beyond 20th week of gestation. Main results and the role of chance A total of 151 women out of 163 completed the primary follow-up after randomization. 12 patients were excluded from the final analysis mainly due to protocol violation and discontinuation of intervention. Each patient contributed to a single cycle in the analysis and given data does not include cumulative pregnancies including surplus frozen embryo transfers. Demographic data including; mean woman age, body mass index, serum AMH, TSH and infertility etiologies were comparable among all groups without statistically significance (p &amp;gt; 0.5) Limitations, reasons for caution Lack of a power analysis is the main limitation of this study, potentially coming with type-1 error. Properly designed and powered RCTs are needed. Wider implications of the findings There have been very limited data available for oral progestogen use particularly in FET cycles, unlike many reports for vaginal and im P. Comperable reproductive outcomes with significantly lower side effect profile of oral progestagen merits further attention in programmed FET cycles. Trial registration number NCT03948022