scholarly journals Frozen embryo transfer: Endometrial preparation by letrozole versus hormone replacement cycle: A randomized clinical trial

Author(s):  
Alamtaj Samsami ◽  
Leila Ghasmpour ◽  
Sara Davoodi ◽  
Shaghayegh Moradi Alamdarloo ◽  
Jamshid Rahmati ◽  
...  

Background: The endometrial preparation with stimulating natural cycles for frozen embryo transfer (FET) have benefits like lower cost and ease of use. Objective: Comparing the clinical outcome of letrozole versus hormone replacement (HR) for endometrial preparation in women with normal menstrual cycles for FET in artificial reproduction techniques. Materials and Methods: A total of 167 participants who had frozen embryos and regular ovulatory cycles were randomly divided into two groups for endometrial preparation. One group (82 women) was stimulated with letrozole 5mg/day and the other group (85 women) was hormonally stimulated by oral estradiol valerate (2 mg three times a day). All participants were followed serially by ultrasonography. Any patient who did not reach optimal endometrial thickness was excluded from the study. Implantation, biochemical and clinical pregnancy and abortion rate were reported. Results: There was no significant difference in the mean age, duration, and primary or secondary infertility, cause of the infertility, number, and quality of transferred embryos between the groups. The mean estradiol level on the day of transfer was 643 ± 217 in the HR group and 547 ± 212 in the letrozole group (P = 0.01), which was significantly different. The clinical pregnancy rate was 38.7 in the letrozole group, higher than the HR group (25.3) but not significantly different (P=0.06). Conclusion: For endometrial preparation in women with a normal cycle, letrozole yields higher pregnancy rate although it is not significant; due to its cost, ease in use, and lower side effects, letrozole is a good choice. Key words: Letrozole, Hormone replacement, Endometrial, Preparation, Frozen, Embryo.

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
A Racca ◽  
S Santos-Ribeiro ◽  
D Panagiotis ◽  
L Boudry ◽  
S Mackens ◽  
...  

Abstract Study question What is the impact of seven days versus fourteen days’ estrogen (E2) priming on the clinical outcome of frozen-embryo-transfer in artificially prepared endometrium (FET-HRT) cycles? Summary answer No significant difference in clinical/ongoing pregnancy rate was observed when comparing 7 versus 14 days of estrogen priming before starting progesterone (P) supplementation. What is known already One (effective) method for endometrial preparation prior to frozen embryo transfer is hormone replacement therapy (HRT), a sequential regimen with E2 and P, which aims to mimic the endocrine exposure of the endometrium in a physiological cycle. The average duration of E2 supplementation is generally 12–14 days, however, this protocol has been arbitrarily chosen whereas, the optimal duration of E2 implementation remains unknown. Study design, size, duration This is a single-center, randomized, controlled, open-label pilot study. All FET-HRT cycles were performed in a tertiary centre between October 2018 and December 2020. Overall, 150 patients were randomized of whom 132 were included in the analysis after screening failure and drop-out. Participants/materials, setting, methods The included patients were randomized into one of 2 groups; group A (7 days of E2 prior to P supplementation) and group B (14 days of E2 prior to P supplementation). Both groups received blastocyst stage embryos for transfer on the 6th day of vaginal P administration. Pregnancy was assessed by an hCG blood test 12 days after FET and clinical pregnancy was confirmed by transvaginal ultrasound at 7 weeks of gestation. Main results and the role of chance Following the exclusion of drop-outs and screening failures, 132 patients were finally included both in group A (69 patients) or group B (63 patients). Demographic characteristics for both groups were comparable. The positive pregnancy rate was 46.4% and 53.9%, (p 0.462) for group A and group B, respectively. With regard to the clinical pregnancy rate at 7 weeks, no statistically significant difference was observed (36.2% vs 36.5% for group A and group B, respectively, p = 0.499). The secondary outcomes of the study (biochemical pregnancy, miscarriage and live birth rate) were also comparable between the two arms for both PP and ITT analysis. Multivariable logistic regression showed that the HRT scheme is not associated with pregnancy rate, however, the P value on the day of ET is significantly associated with the pregnancy outcome. Limitations, reasons for caution This study was designed as a proof of principle trial with a limited study population and therefore underpowered to determine the superiority of one intervention over another. Instead, the purpose of the present study was to explore trends in outcome differences and to allow us to safely design larger RCTs. Wider implications of the findings: The results of this study give the confidence to perform larger-scale RCTs to confirm whether a FET-HRT can be performed safely in a shorter time frame, thus, reducing the TTP, while maintaining comparable pregnancy and live birth rates. Trial registration number NCT03930706


2021 ◽  
Author(s):  
Li Li ◽  
Dan-Dan Gao ◽  
Yi Zhang ◽  
Jing-Yan Song ◽  
Zhen-Gao Sun

Abstract Objective The principal purpose of this study was to compare reproductive outcomes for stimulated cycles (STC) and hormone replacement cycles (HRC) for endometrial preparation before frozen-thawed embryo transfer (FET) in young women with polycystic ovary syndrome (PCOS). Methods We conducted a retrospective study of 1434 FET cycles from January, 2017 to March, 2020 in our reproductive center, in which stimulated and hormone replacement cycles were used for endometrial preparation. Pregnancy outcomes of couples undergoing routine STC-FET or HRC-FET were analyzed before and after propensity score matching (PSM). Results Data on 1234 HRC protocols (86% of the total) and 200 STC protocols (14%) were collected. After PSM, 199 patients were included in both groups, respectively. There was no significant difference in positive pregnancy rate (52.7% vs. 54.8%, p = 0.763), clinical pregnancy rate (51.8% vs. 52.8%, p = 0.841), live birth rate (45.2% vs. 43.7%, p = 0.762), pregnancy loss rate (9.7% vs. 16.2%, p = 0.164) and ectopic pregnancy rate (1.5% vs. 0.5%, p = 0.615) between STC protocols and HRC protocols. Conclusion STC for endometrial preparation had similar pregnancy outcomes compared with HRC protocols by excluding heterogeneous factors after PSM. Evidence is available which shows that for young women with PCOS who were undergoing in-vitro fertilization, HRC could be a reasonable choice for patients who are unwilling to accept injections. Additionally, STC may offer more flexibility for young PCOS patients and reproductive centres.


Author(s):  
Yanbo Du ◽  
Lei Yan ◽  
Mei Sun ◽  
Yan Sheng ◽  
Xiufang Li ◽  
...  

Abstract Purpose To investigate the effect of hCG in hormone replacement regime for frozen thawed embryo transfer in women with endometriosis. Methods We performed a retrospective, database-searched cohort study. The data of endometriosis patients who underwent frozen embryo transfer between 1/1/2009-31/8/2018 were collected. According to the protocols for frozen embryo transfer cycle, these patients were divided into two groups: Control group(n=305), and hCG group(n=362). And clinical pregnancy rate, live birth rate, early abortion rate, late abortion rate and ectopic pregnancy rate were compared between the two groups. Results There was a significant increase in clinical pregnancy rate in hCG group (56.6% vs. 48.2%, p=0.035) compared to the control group. And the live birth rate in hCG group (43.5% vs. 37.4%, p=0.113) also elevated, but the difference is statistically insignificant. Conclusion hCG administration in hormone replacement regime for FET increase the pregnancy rate in women with endometriosis.


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Alessio Paffoni ◽  
Marco Reschini ◽  
Valerio Pisaturo ◽  
Cristina Guarneri ◽  
Simone Palini ◽  
...  

Abstract Background Total fertilization failure represents a particularly frustrating condition for couples undergoing in vitro fertilization. With the aim of reducing the occurrence of total fertilization failure, intracytoplasmic sperm injection (ICSI) has become the first choice over conventional in vitro fertilization (IVF) procedures although evidence of improved results is still debated and its use in couples without male factor infertility is not recommended. Among the strategies potentially useful to promote the use of conventional IVF, we herein call attention to the late rescue ICSI, which consists in performing ICSI after 18–24 h from conventional insemination on oocytes that show no signs of fertilization. This treatment has however been reported to be associated with a low success rate until recent observations that embryos derived from late rescue ICSI may be transferred after cryopreservation in a frozen-thawed cycle with improved results. The aim of the present study was to assess whether frozen embryos deriving from rescue ICSI performed about 24 h after conventional IVF may represent a valuable option for couples experiencing fertilization failure. Methods A systematic review on the efficacy of late rescue ICSI was performed consulting PUBMED and EMBASE. Results Including twenty-two original studies, we showed that clinical pregnancy rate per embryo transfer and implantation rate obtainable with fresh embryo transfers after rescue ICSI are not satisfactory being equal to 10 and 5%, respectively. The transfer of cryopreserved rescue ICSI embryos seems to offer a substantial improvement of success rates, with pregnancy rate per embryo transfer and implantation rate equal to 36 and 18%, respectively. Coupling rescue ICSI with frozen embryo transfer may ameliorate the clinical pregnancy rate for embryo transfer with an Odds Ratio = 4.7 (95% CI:2.6–8.6). Conclusion Results of the present review support the idea that r-ICSI coupled with frozen embryo transfer may overcome most of the technical and biological issues associated with fresh transfer after late r-ICSI, thus possibly representing an efficient procedure for couples experiencing fertilization failure following conventional IVF cycles. Trial registration Prospero registration ID: CRD42021239026.


2021 ◽  
Author(s):  
Manuel Álvarez ◽  
Sofía Gaggiotti-Marre ◽  
Francisca Martínez ◽  
Lluc Coll ◽  
Sandra García ◽  
...  

Abstract STUDY QUESTION Does an individualised luteal phase support (iLPS), according to serum progesterone (P4) level the day prior to euploid frozen embryo transfer (FET), improve pregnancy outcomes when started on the day previous to embryo transfer? SUMMARY ANSWER Patients with low serum P4 the day prior to euploid FET can benefit from the addition of daily subcutaneous P4 injections (Psc), when started the day prior to FET, and achieve similar reproductive outcomes compared to those with initial adequate P4 levels. WHAT IS KNOWN ALREADY The ratio between FET/IVF has spectacularly increased in the last years mainly thanks to the pursuit of an ovarian hyperstimulation syndrome free clinic and the development of preimplantation genetic testing (PGT). There is currently a big concern regarding the endometrial preparation for FET, especially in relation to serum P4 levels around the time of embryo transfer. Several studies have described impaired pregnancy outcomes in those patients with low P4 levels around the time of FET, considering 10 ng/ml as one of the most accepted reference values. To date, no prospective study has been designed to compare the reproductive outcomes between patients with adequate P4 the day previous to euploid FET and those with low, but restored P4 levels on the transfer day after iLPS through daily Psc started on the day previous to FET. STUDY DESIGN, SIZE, DURATION A prospective observational study was conducted at a university-affiliated fertility centre between November 2018 and January 2020 in patients undergoing PGT for aneuploidies (PGT-A) IVF cycles and a subsequent FET under hormone replacement treatment (HRT). A total of 574 cycles (453 patients) were analysed: 348 cycles (leading to 342 euploid FET) with adequate P4 on the day previous to FET, and 226 cycles (leading to 220 euploid FET) under iLPS after low P4 on the previous day to FET, but restored P4 levels on the transfer day. PARTICIPANTS/MATERIALS, SETTING, METHODS Overall we included 574 HRT FET cycles (453 patients). Standard HRT was used for endometrial preparation. P4 levels were measured the day previous to euploid FET. P4 > 10.6 ng/ml was considered as adequate and euploid FET was performed on the following day (FET Group 1). P4 < 10.6 ng/ml was considered as low, iLPS was added in the form of daily Psc injections, and a new P4 analysis was performed on the following day. FET was only performed on the same day when a restored P4 > 10.6 ng/ml was achieved (98.2% of cases) (FET Group 2). MAIN RESULTS AND THE ROLE OF CHANCE Patient’s demographics and cycle parameters were comparable between both euploid FET groups (FET Group 1 and FET Group 2) in terms of age, weight, oestradiol and P4 levels and number of embryos transferred. No statistically significant differences were found in terms of clinical pregnancy rate (56.4% vs 59.1%: rate difference (RD) −2.7%, 95% CI [−11.4; 6.0]), ongoing pregnancy rate (49.4% vs 53.6%: RD −4.2%, 95% CI [−13.1; 4.7]) or live birth rate (49.1% vs 52.3%: RD −3.2%, 95% CI [−12; 5.7]). No significant differences were also found according to miscarriage rate (12.4% vs 9.2%: RD 3.2%, 95% CI [−4.3; 10.7]). LIMITATIONS, REASONS FOR CAUTION Only iLPS through daily Psc was evaluated. The time for Psc injection was not stated and no serum P4 determinations were performed once the pregnancy was achieved. WIDER IMPLICATIONS OF THE FINDINGS Our study provides information regarding an ‘opportunity window’ for improved ongoing pregnancy rates and miscarriage rates through a daily Psc injection in cases of inadequate P4 levels the day previous to FET (P4 < 10.6 ng/ml) and restored values the day of FET (P4 > 10.6 ng/ml). Only euploid FET under HRT were considered, avoiding one of the main reasons of miscarriage and implantation failure and overcoming confounding factors such as female age, embryo quality or ovarian stimulation protocols. STUDY FUNDING/COMPETING INTEREST(S) No external funding was received. B.C. reports personal fees from MSD, Merck Serono, Ferring Pharmaceuticals, IBSA and Gedeon Richter outside the submitted work. N.P. reports grants and personal fees from MSD, Merck Serono, Ferring Pharmaceuticals, Theramex and Besins International and personal fees from IBSA and Gedeon Richter outside the submitted work. The remaining authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER NCT03740568.


2016 ◽  
Vol 33 (12) ◽  
pp. 1553-1557 ◽  
Author(s):  
Jigal Haas ◽  
Jim Meriano ◽  
Carl Laskin ◽  
Yaakov Bentov ◽  
Eran Barzilay ◽  
...  

Author(s):  
Dr. Narmadha. R ◽  
Dr . Manjula ◽  
Dr. N.Sanjeeva Reddy ◽  
Dr. Sindhuja. N.S

The implantation of the embryo into the uterus requires hatching from its zona pellucida (ZP). The inability of the embryo to break its zona pellucida is considered as a factor for implantation failure. Assisted hatching (AH) is performed to make it easier for natural hatching to occur, also providing early embryoendometrium contact, which favors the embryos implantation into the uterus. To evaluate the effect of laser assisted hatching (LAH) on pregnancy rate in frozen embryo transfer cycle.  Materials & methods: In a prospective observational study a total of 80 patients who underwent frozen embryo transfer(FET) cycles were included in the study. Patients were divided into Laser assisted hatching group (LAH) and no LAH group. In the LAH group, zona thinning was done with the help of laser just prior to the embryo transfer. In the control group no hatching was done before transfer. The main outcome measures were pregnancy rate & implantation rate. The baseline characteristics of the 80 patients included in the study ie.,LAH group (n=40) vs no LAH group (n=40),the mean age ( 30.855.4 vs 333.9),mean BMI (25.64.1 vs 27.94.5),duration of infertility ( 6.184.1 vs 8.534.7) , number of embryos transferred (2.750.8 vs 2.70.72) respectively. Younger women < 30 years in no LAH group had higher pregnancy rate compared to the LAH group. Between the two groups, patients between 31-35 years in LAH group had higher pregnancy rate compared to no LAH group. The pregnancy rate (42.85% vs 54.5%) in LAH group of women >35years found lower than the no LAH group. LAH seems to be beneficial in women between 31- 35 years of age group, but LAH does not seem to be beneficial in women > 35 years of age. There is slight increase in pregnancy rates with laser assisted zona thinning in frozen transfer cycle, but it is not statistically significant.


Author(s):  
Monique Atkinson ◽  
Jenny Crittenden ◽  
Howard Smith ◽  
Cecilia Sjoblom Ahlstrom

Objective: To examine the pregnancy outcomes from frozen embryo transfer (FET) cycles using different endometrial preparation regimens, compared to ovulation induction with letrozole (letrozole OI). Design: Retrospective cohort study. Setting: Fertility centre in Sydney, Australia. Patient(s): 6060 frozen embryo transfer cycles. Interventions: Cycles were stratified into one of four ways to achieve endometrial preparation. These were either a natural, letrozole OI, OI with follicle stimulating hormone (FSH OI) or a programmed cycle. Main Outcome Measure(s): The primary outcome was live birth rate per embryo transfer (LBR). Secondary outcomes included clinical pregnancy and biochemical pregnancy rates, adverse events including miscarriage, ectopic pregnancy, stillbirth, neonatal death and multiple births. Ovarian stimulation parameters were also analysed including time taken to reach the luteal phase and the number of blood or urine tests required for monitoring of the cycle. Results: The LBR following letrozole OI cycles was higher when compared to natural cycles (OR 1.27 (1.07 – 1.49)) and programmed cycles (OR 2.36 (1.67 – 3.34)). There was no significant difference between letrozole OI and FSH OI LBR (OR 0.99 (0.76 – 1.28)). An improved LBR with letrozole OI compared to natural cycles was maintained when only women with a normal length cycle were considered (OR 1.44 (1.10 – 1.89)). There was a significant reduction in miscarriage rates when letrozole OI was compared to programmed cycles (OR 0.46 (0.26 – 0.83)). Conclusion(s): The use of letrozole OI for endometrial preparation in an FET cycle may be associated with higher LBR and lower miscarriage rate, compared to using a programmed cycle.


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