Luteal phase support does not improve the clinical pregnancy rate of natural cycle frozen-thawed embryo transfer: a retrospective analysis

Background: Luteal-phase support is a complex and controversial issue in the field of reproductive management. Objective: To compare the safety and efficacy of low-dose subcutaneous progesterone with the vaginal progesterone for luteal-phase support in patients undergoing rozenthawed embryo transfer. Materials and Methods: In this cross-sectional study, information related to 77 women that had frozen-thawed embryo transfer was reviewed. The patients were divided into two groups based on the route of progesterone administration used as a luteal-phase support. When the endometrial thickness reached ≥ 8 mm, in one group progesterone (Prolutex) 25 mg/ daily subcutaneous and in another group, vaginal progesterone (Cyclogest®) 400 mg twice or (Endometrin®) 100 mg thrice daily, were administrated and continued until menstruation or in case of clinical pregnancy for 8 wk after the embryo transfer when the fetal heart activity was detected by ultrasonography. Results: The patient’s characteristics were matched and there was no significant difference. The chemical and clinical pregnancy rate was higher in the vaginal progesterone group compared to the prolutex group, but statistically unnoticeable, (40% vs. 29.6%, p = 0.367) and (28% vs. 22.2%, p = 0.581), respectively. C Conclusion: The findings of this study demonstrate that the new subcutaneous progesterone can be a good alternative for intramuscular progesterone in women that dislike and do not accept vaginal formulations as luteal-phase support in assisted reproductive technology. Key words: Progesterone, Subcutaneous, Vaginal, Pregnancy.

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Does Estradiol Orally and Vaginally Administered Together Impact Live Birth and Neonatal Outcome in Artificial Frozen-thawed Embryo Transfer Cycles: A Retrospective Cohort Study

10.21203/rs.3.rs-42796/v1 ◽

2020 ◽

Author(s):

Yuan Liu ◽

Yixia Yang ◽

Xinting Zhou ◽

Yanmei Hu ◽

Yu Wu

Keyword(s):

Pregnancy Rate ◽

Preterm Delivery ◽

Embryo Transfer ◽

Live Birth ◽

Clinical Pregnancy ◽

Clinical Pregnancy Rate ◽

Delivery Rate ◽

Serum Estradiol ◽

Frozen Thawed Embryo Transfer ◽

Thawed Embryo Transfer

Abstract Background: Previous studies have demonstrated that newborns from fresh embryo transfer are with higher risk of small for gestation (SGA) rate than those from frozen-thawed embryo transfer (FET). It is suggested that supraphysiologic serum estradiol in controlled ovarian stimulation (COS)is one of reasons. Out study aims to investigate whether exogenous estradiol delivered regimens have an impact on live birth rate and singleton birthweight in hormone replacement (HRT)-FET cycles.Methods:This retrospective study involved patients undergoing their first FET with HRT endometrium preparation followed by two cleavage-staged embryos transfer, comparing orally and vaginal estradiol tablets (OVE) group versus oral estradiol tablets (OE) group from January 2015 to December 2018 at our center. A total of 792 patients fulfilled the criteria, including 282 live birth singletons. Live birth was the primary outcome. Secondary outcome included clinical pregnancy rate, singleton birthweight, large for gestational age (LGA) rate, SGA rate, preterm delivery rate. Results:Patients in OVE group achieved higher serum estradiol level with more days of estradiol treatment. No difference in live birth (Adjusted OR 1.327; 95%CI 0.982, 1.794, p=0.066) and clinical pregnancy rate (Adjusted OR 1.278; 95%CI 0.937, 1.743, p=0.121) was found between OVE and OE groups. Estradiol route did not affect birth weight (β=-30.962, SE=68.723, p=0.653), the odds of LGA (Adjusted OR 1.165; 95%CI 0.545, 2.490, p=0.694), the odds of SGA (Adjusted OR 0.569; 95%CI 0.096, 3.369, p=0.535) or the preterm delivery rate (Adjusted OR 0.969; 95%CI 0.292, 3.214, p=0.959).Conclusion:Estrogen orally and vaginally together did not have an impact on clinical outcomes and singleton birthweight compared to estrogen orally taken, but was accompanied with relative higher serum E2 level and potential maternal undesirable risks.

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Twice vitrification-warming procedures has no effect on frozen-thawed embryo transfer outcomes

10.21203/rs.3.rs-1059310/v1 ◽

2021 ◽

Author(s):

xiaoyue Shen ◽

Min Ding ◽

Yuan Yan ◽

Shanshan Wang ◽

jianjun Zhou ◽

...

Keyword(s):

Pregnancy Rate ◽

Embryo Transfer ◽

Live Birth ◽

Birth Rate ◽

Live Birth Rate ◽

Clinical Pregnancy ◽

Clinical Pregnancy Rate ◽

Miscarriage Rate ◽

Frozen Thawed Embryo Transfer ◽

Thawed Embryo Transfer

Abstract Background To evaluate the frozen-thawed embryo transfer (FET) outcomes of repeated cryopreservation by vitrification of blastocysts derived from vitrified-warmed day3 embryos in patients who experienced implantation failure previously. Methods We retrospect the files of patients who underwent single frozen-thawed blastocyst transfer cycles in our reproductive medical center from January 2013 to December 2019. 127 patients transfer of vitrified-warmed blastocysts derived from vitrified-warmed day3 embryos were defined as twice-cryopreserved group. 1567 patients who transfer blastocysts that had experienced once vitrified-warmed were used as once-cryopreserved group. None of them was pregnant at the previous FET. The outcomes were compared between two groups after a 1:1 propensity score matching (PSM). Results The clinical pregnancy rate was 52.76%, live birth rate was 43.31% in twice-cryopreserved group. After PSM,108 pairs of patients were generated for comparison. The clinical pregnancy rate, live birth rate or miscarriage rate was not significantly different between two groups. Logistic regression analysis indicated that double vitrification-warming procedures did not affect FET outcomes in terms of clinical pregnancy rate (OR 0.83, 95%CI 0.47-1.42), live birth rate (OR 0.93, 95%CI 0.54-1.59), miscarriage rate (OR 0.72 95%CI 0.28-1.85). Furthermore, the pregnancy complications rate, gestational age or neonatal abnormalities rate between two groups was also comparable, while twice vitrification-warming procedures might increase the macrosomia rate (19.6% vs. 6.3%, P = 0.05). Conclusion Transfer of double vitrified-warmed embryo at cleavage stage and subsequent blastocyst stage did not affect live birth rate and neonatal abnormalities rate, but there was a tendency to increase macrosomia rate, which needs further investigation.

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Pretreatment With a Long-acting GnRH Agonist in Early Follicular Phase Increases Clinical Pregnancy Rate in Frozen-thawed Embryo Transfer Cycles

10.21203/rs.3.rs-864572/v1 ◽

2021 ◽

Author(s):

Bin xu ◽

Jing Zhao ◽

Zhaojuan Hou ◽

Nenghui Liu ◽

Yanping Li

Keyword(s):

Pregnancy Rate ◽

Embryo Transfer ◽

Hormone Replacement ◽

Follicular Phase ◽

Clinical Pregnancy ◽

Clinical Pregnancy Rate ◽

Early Follicular Phase ◽

Long Acting ◽

Frozen Thawed Embryo Transfer ◽

Thawed Embryo Transfer

Abstract Background: It is controversial whether gonadotropin-releasing hormone agonist (GnRHa) pretreatment can benefit the pregnancy outcomes in frozen-thawed embryo transfer (FET) cycles. In most of studies, GnRHa was administered during the mid-luteal phase for pretreatment. Few studies focus on FET cycles with GnRHa administered in early follicle phase.Methods: The retrospective cohort study was conducted in a university-affiliated IVF center. 630 patients in the GnRHa FET group and 1141 patients in the hormone replacement treatment (HRT) FET without GnRHa group from October 2017 to March 2019 were included. The menstruation cycle of these patients was irregular. Results: There were no differences observed between the two groups in patient’s characteristics. However, the GnRHa FET group showed a higher percentage of endometrium with triple line pattern (94.8% vs 89.6%, p<0.001) on the day of progesterone administration, and an increased implantation rate (34.7% vs 30%, p<0.01), biochemical pregnancy rate (60.6% vs 54.3%, p = 0.009), and clinical pregnancy rate (49.8% vs 43.3%, p = 0.008), as compared to that in the HRT FET cycles with similar endometrial thickness, ectopic pregnancy rate, and early miscarriage rate. Binary logistic regression analysis showed the GnRHa FET group to be associated with an increased chance of clinical pregnancy rate compared with HRT FET without GnRHa group (P=0.014, odds ratio [OR] 1.30, 95% confidence interval [CI] 1.06-1.61).Conclusions: Pretreatment with a long-acting GnRHa in early follicular phase can improve the clinical outcome of the FET cycles. However, further randomized control trials (RCTs) will be needed to verify these results.

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P–629 Is spontaneous ovulation better than induced ovulation for frozen-thawed embryo transfer cycle?

Human Reproduction ◽

10.1093/humrep/deab130.628 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

P K Sim ◽

P Nadkarni

Keyword(s):

Pregnancy Rate ◽

Embryo Transfer ◽

Clinical Pregnancy ◽

Clinical Pregnancy Rate ◽

Ongoing Pregnancy ◽

Ongoing Pregnancy Rate ◽

Significance Level ◽

Induced Ovulation ◽

Frozen Thawed Embryo Transfer ◽

Thawed Embryo Transfer

Abstract Study question Between spontaneous ovulation (SPO) and induced ovulation (INO) comparing clinical pregnancy rate and ongoing pregnancy rate for frozen-thawed embryo transfer (FET) cycle, which is better? Summary answer Both spontaneous ovulation and induced ovulation protocols showed no significant difference in clinical pregnancy rates and ongoing pregnancy rates. What is known already Recent practice worldwide is moving towards elective freezing of all embryos and subsequent frozen-thawed transfer, both for a perceived higher pregnancy rate as well as the significant reduction of ovarian hyperstimulation. The timing of FET can be determined by either detecting the spontaneous Luteinizing Hormone surge (SPO group) or by the administration of hCG (INO group). There is still an ongoing debate to determine which is the best protocol for frozen-thawed embryo transfer in the non-hormone replacement therapy (non-HRT) cycle. Study design, size, duration This retrospective study included 500 FET cycles for patients who had regular menses between June 2017 and June 2020. The FET cycles were grouped by type as follows: SPO (n = 281) and INO (n = 219). The primary outcome was the clinical pregnancy rate and the secondary outcome was ongoing pregnancy rate. Ongoing pregnancy is defined as a viable intrauterine pregnancy at 12 weeks of gestation confirmed on an ultrasound scan. Participants/materials, setting, methods This study was conducted in a single IVF centre. Vitrification was used as the cryopreservation method. To standardize outcome measures, only patients having single blastocyst transfer and aged under 38 years old were included. The average age of the patient was 32.9. Gamete donation, embryo donation, pre-implantation testing and assisted hatching cycles were also excluded from the analysis. Categorical data were analysed using Chi-square test SPSS version 25. Main results and the role of chance Clinical pregnancy rate for SPO group was 54.8% (154/281) versus 52.9% (116/219) in INO group. Even though clinical pregnancy rate was higher in SPO group as compared to INO group, it did not reach significance level (ꭓ2 = 0.17, p = 0.68). As all patients had single blastocyst transferred, the implantation rate was the same as clinical pregnancy rate. Ongoing pregnancy rate was also found higher in SPO group as compared to INO group (135/281, 48.0% and 97/219, 44.3% respectively) but again failed to reach significance level (ꭓ2 = 0.70, p = 0.40). Limitations, reasons for caution The retrospective nature of the study and therefore, the analysis was not adjusted for confounding factors such as blastocyst grading, etiology of infertility, and ethnicity of patients. Wider implications of the findings: In natural cycle, both spontaneous ovulation and induced ovulation protocols had the same pregnancy outcomes for frozen-thawed embryo transfer. However, induced ovulation can facilitate in scheduling FET timing to avoid weekends and public holidays, if necessary. Trial registration number Not applicable

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Endometrium immunomodulation by intrauterine insemination administration of treated peripheral blood mononuclear cell prior frozen/thawed embryos in patients with repeated implantation failure

Zygote ◽

10.1017/s0967199419000145 ◽

2019 ◽

Vol 27 (4) ◽

pp. 214-218 ◽

Cited By ~ 1

Author(s):

Fattaneh Farifteh Nobijari ◽

Seyedeh Soheila Arefi ◽

Ashraf Moini ◽

Robabeh Taheripanah ◽

Elham Fazeli ◽

...

Keyword(s):

Pregnancy Rate ◽

Embryo Transfer ◽

Peripheral Blood ◽

Clinical Pregnancy ◽

Clinical Pregnancy Rate ◽

Control Group ◽

Peripheral Blood Mononuclear ◽

Significant Difference ◽

Frozen Thawed Embryo Transfer ◽

Thawed Embryo Transfer

SummaryIn assisted reproductive technology (ART) programmes, approximately 10% of infertile patients have at least two or three repeated implantation failures (RIFs) after an in vitro fertilization (IVF) protocol. Successful implantation mainly depends on local immune tolerance mechanisms involving a spectrum of cytokines, interleukins and growth factors. The latter have played pivotal roles in the recruitment of immune cells (and notably T-lymphocyte cells). In total, 250 couples participating in frozen–thawed embryo transfer programme were incorporated in a randomized clinical trial (peripheral blood mononuclear cells (PBMC) subgroup: n=122; control subgroup: n=128). In the PBMC group, a blood sample was collected 5 days before the scheduled frozen–thawed embryo transfer; PBMCs were isolated using Ficoll separation and then cultured for 72 h. Two days prior to embryo transfer, 0.4 ml of cultured PBMCs were transferred into the patient’s uterus. Although the clinical pregnancy rate was higher in the PBMC group (34.4%) than in the control group (23.4%), this difference was not statistically significant (P=0.05 in a chi-squared test). Nevertheless, when we limited the analysis to patients with ≥3 RIFs (n=138), there was a significant difference in the clinical pregnancy rate between the PBMC group (38.6%) and the control group (19.7%; P=0.01). Our results imply that PBMC transfer can be part of effective fertility treatment for patients with RIF.

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A Novel Promising Endometrial Preparation Protocol for Frozen-Thawed Embryo Transfer: A Randomized Controlled Trial

Frontiers in Endocrinology ◽

10.3389/fendo.2021.730059 ◽

2021 ◽

Vol 12 ◽

Author(s):

Jian-Chun Li ◽

Yan-Hong Wang ◽

li-Ying Peng ◽

Yun Zhou ◽

Shi-Bin Chao

Keyword(s):

Pregnancy Rate ◽

Embryo Transfer ◽

Pilot Trial ◽

Implantation Rate ◽

Clinical Pregnancy ◽

Clinical Pregnancy Rate ◽

Randomized Controlled ◽

Endometrial Preparation ◽

Frozen Thawed Embryo Transfer ◽

Thawed Embryo Transfer

BackgroundIn recent years frozen-thawed embryo transfer (FET) has played an increasingly important role in ART, but there is limited consensus on the most effective method of endometrial preparation (EP) for FET. Inspired by significantly higher implantation rate and clinical pregnancy rate of the depot GnRH-a protocol, we proposed a novel EP protocol named down-regulation ovulation-induction (DROI) aimed to improve pregnancy outcomes of FET.MethodsThis was a single-center, randomized controlled pilot trial. A total of 307 patients with freeze-all strategy scheduled for first FET were enrolled in the study. A total 261 embryos were transferred in DROI-FET group including 156 patients and 266 embryos were transferred in mNC-FET group including 151 patients. Reproductive outcomes were compared between the two groups.ResultsThe basic characteristics of patients, and the average number, quality and stage of embryos transferred were comparable between the two groups. Our primary outcome, implantation rate(IR) in DROI-FET group, was significantly higher than that of the mNC-FET group (54.41% versus 35.71%, P<0.01). The clinical pregnancy rate (CPR) and ongoing pregnancy rate (OPR) in DROI-FET group was also higher than that in mNC-FET group (69.87% versus 50.33%, P<0.01; 64.10% versus 42.38%, P<0.01).Conclusion(s)Compared to existing endometrial preparation methods, the DROI protocol might be the more efficient and promising protocol.

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Comparison of four protocols for luteal phase support in frozen-thawed Embryo transfer cycles: a randomized clinical trial

Archives of Gynecology and Obstetrics ◽

10.1007/s00404-016-4217-4 ◽

2016 ◽

Vol 295 (1) ◽

pp. 239-246 ◽

Cited By ~ 18

Author(s):

Afsoon Zarei ◽

Parastoo Sohail ◽

Mohammad Ebrahim Parsanezhad ◽

Saeed Alborzi ◽

Alamtaj Samsami ◽

...

Keyword(s):

Clinical Trial ◽

Randomized Clinical Trial ◽

Embryo Transfer ◽

Luteal Phase ◽

Luteal Phase Support ◽

Frozen Thawed Embryo Transfer ◽

Thawed Embryo Transfer

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Luteal Phase Progesterone Support Does Not Improve Ongoing Pregnancies in True Natural Cycle Cryopreserved Blastocyst Stage Embryo Transfers

10.21203/rs.3.rs-31243/v1 ◽

2020 ◽

Author(s):

Ian Waldman ◽

Catherine Racowsky ◽

Emily Disler ◽

Ann Thomas ◽

Lanes Andrea ◽

...

Keyword(s):

Pregnancy Rate ◽

Luteal Phase ◽

Abortion Rate ◽

Clinical Pregnancy ◽

Natural Cycle ◽

Ongoing Pregnancy ◽

Ongoing Pregnancy Rate ◽

Luteal Phase Support ◽

Progesterone Supplementation ◽

Natural Cycles

Abstract Background: More than 67% of all embryos transferred in the United States involve frozen-thawed embryos. Progesterone supplementation is necessary in medicated cycles in order to luteinize the endometrium and prepare it for implantation, but little data is available if this is necessary in true natural cycles. We evaluated the use of progesterone luteal phase supplementation for cryopreserved/warmed blastocyst transfers in natural cycles not using an ovulatory trigger.Methods: Retrospective cohort study in a single academic medical center. We studied the use of progesterone supplementation beginning in the luteal phase and continued until 10 weeks gestational age in patients undergoing true natural cycle cryopreserved blastocyst transfer. Our outcome measures were ongoing pregnancy rate, positive serum beta human chorionic gonadotropin (HCG) level, implantation rate, clinical pregnancy rate, miscarriage/abortion rate, ectopic pregnancy rate, and multifetal gestation rate. Categorical data were analyzed utilizing Fisher’s exact test and non-parametric data were analyzed using the Wilcoxon rank sum test. We a priori adjusted for age.Results: 229 patients were included in the analysis with 149 receiving luteal phase progesterone supplementation and 80 receiving no luteal phase support. Patient demographic and cycle characteristics, and embryo quality were similar between the two groups. No difference was seen in ongoing pregnancy rate (49.0% vs. 47.5%, p=0.8738), clinical pregnancy rate (50.3% vs. 47.5%, p= 0.7483), positive HCG rate (62.4% vs. 57.5%, p=0.5965), miscarriage/abortion rate (5.4% vs. 2.5%, p=0.2622), ectopic pregnancy rate (0% vs. 1.3%, p=0.3493), or multifetal gestations (7.4% vs. 3.8%, p=0.3166).Conclusion(s): The addition of progesterone luteal phase support in true natural cycle cryopreserved blastocyst transfers does not improve cycle outcomes. Capsule: Progesterone supplementation as luteal phase support in true natural cycle cryopreserved blastocyst transfers does not improve ongoing pregnancies.

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