scholarly journals Optimal Endometrial Preparation Protocols for Frozen-thawed Embryo Transfer Cycles by Maternal Age

Author(s):  
Qizhen Zheng ◽  
Hongzhan Zhang ◽  
Shiru Xu ◽  
Shan Xiao ◽  
Xuejin Wang ◽  
...  

Abstract Background: It is paramount to consider the appropriate preparation of the endometrium to receive the transferred embryos as the amount of frozen embryo transfer (FET) cycles is increasing worldwide. However, there remains lack of evidence about what is the most optimal protocol of endometrial preparation regarding pregnancy outcomes in different subgroup of infertile women. This retrospective cohort study was aim to explore the best endometrial preparation protocols among different maternal age groups.Methods: A total of 16870 FET cycles were categorized into three groups based on endometrial preparation protocols: Natural cycle (NC n=3893), artificial cycles (AC, n=11459) and AC with pretreatment with GnRH-a (AC+GnRH-a, n=1518). Logistic regression was performed to investigate the independent effect of endometrial preparation protocols on IVF pregnancy outcomes. Subgroup analyses were conducted to evaluate the most optimal endometrial preparation protocols for different maternal age groups.Results: In overall populations, after controlling for potential confounders, the incidence of live birth (NC as reference; AC: adjusted odds ratio (aOR) =0.840, 95%CI 0.774-0.912; AC+GnRHa: aOR=0.907, 95%CI 0.795-1.034) in NC was significantly higher than that of AC, while comparable to that of AC+GnRH-a. The early miscarriage rate (AC: aOR=1.413, 95%CI 1.220-1.638; AC+GnRHa: aOR=1.537, 95%CI 1.232-1.919) was significantly lower in NC compared to either AC group. In younger women, the live birth rates (AC: aOR=0.894, 95%CI 0.799-1.001; AC+GnRHa: aOR=1.111, 95%CI 0.923-1.337) were comparable between the three groups, with a slightly higher in AC+GnRH-a. Early miscarriage rate was only significantly lower in NC compared to that of AC without GnRH-a (aOR=1.452, 95%CI 1.159-1.820). While in older women, the incidence of live birth (AC: aOR=0.811, 95%CI 0.718-0.916; AC+GnRHa: aOR=0.760, 95%CI 0.626-0.923) was significantly higher, and early miscarriage (AC: aOR=1.358, 95%CI 1.114-1.655; AC+GnRHa: aOR=1.717, 95%CI 1.279-2.305) was significantly lower in NC compared to those of two AC groups.Conclusions: NC protocol is associated with lower early miscarriage late in overall IVF population. There is a mild favor of AC+GnRH-a in younger women, while the priority of NC is remarkable in older women. Maternal age should be a considerable factor when determine endometrial preparation method for FET.

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Junan Meng ◽  
Mengchen Zhu ◽  
Wenjuan Shen ◽  
Xiaomin Huang ◽  
Haixiang Sun ◽  
...  

Abstract Background It is still uncertain whether surgical evacuation adversely affects subsequent embryo transfer. The present study aims to assess the influence of surgical evacuation on the pregnancy outcomes of subsequent embryo transfer cycle following first trimester miscarriage in an initial in vitro fertilization and embryo transfer (IVF-ET) cycle. Methods A total of 645 patients who underwent their first trimester miscarriage in an initial IVF cycle between January 2013 and May 2016 in Nanjing Drum Tower Hospital were enrolled. Surgical evacuation was performed when the products of conception were retained more than 8 h after medical evacuation. Characteristics and pregnancy outcomes were compared between surgical evacuation patients and no surgical evacuation patients. The pregnancy outcomes following surgical evacuation were further compared between patients with ≥ 8 mm or < 8 mm endometrial thickness (EMT), and with the different EMT changes. Results The EMT in the subsequent embryo transfer cycle of surgical evacuation group was much thinner when compared with that in the no surgical evacuation group (9.0 ± 1.6 mm vs. 9.4 ± 1.9 mm, P = 0.01). There was no significant difference in implantation rate, clinical pregnancy rate, live birth rate or miscarriage rate between surgical evacuation group and no surgical evacuation group (P > 0.05). The live birth rate was higher in EMT ≥ 8 mm group when compared to < 8 mm group in surgical evacuation patients (43.0% vs. 17.4%, P < 0.05). Conclusions There was no significant difference in the pregnancy outcomes of subsequent embryo transfer cycle between surgical evacuation patients and no surgical evacuation patients. Surgical evacuation led to the decrease of EMT, especially when the EMT < 8 mm was association with a lower live birth rate.


2021 ◽  
Author(s):  
Meilan Mo ◽  
Qizhen Zheng ◽  
Hongzhan Zhang ◽  
Shiru Xu ◽  
Fen Xu ◽  
...  

Abstract Objective: This retrospective study aimed to explore the optimal endometrial preparation method in women with intrauterine adhesions (IUAs).Method: A total of 882 frozen-thawed embryo transfer (FET) cycles were categorized into three groups based on endometrial preparation methods: hormone replacing therapy cycle (HRT, n=636), natural cycle (NC n=174), and HRT with GnRH-a pretreatment (HRT+GnRH-a, n=72. Logistic regression was performed to investigate the association between cycle regimens and pregnancy outcomes. Subgroup analysis of IUAs combined with thin endometrium (≤7mm) was also performed.Results: HRT with GnRH-a pretreatment was associated with higher incidences of clinical pregnancy, ongoing pregnancy, and live birth, but lower early miscarriage compared with either HRT or NC. Logistic regression indicated that after controlling for potential confounders, the incidences of live birth (HRT+GnRH-a as reference; NC: aOR=0.577, 95%CI 0.304-1.093; HRT: aOR=0.434, 95%CI 0.247-0.765) and ongoing pregnancy (NC: aOR=0.614, 95%CI 0.324-1.165; HRT: aOR=0.470, 95%CI 0.267-0.829) remained significantly higher in HRT+GnRH-a compared to those in HRT, but comparable to those in NC. While there was no significant difference with respect to the clinical pregnancy rate (NC: aOR=0.695, 95%CI 0.374-1.291; HRT: aOR=0.650, 95%CI 0.374-1.127) and early miscarriage rate (NC: aOR=1.734, 95%CI 0.417-7.175; HRT: aOR=2.594, 95%CI 0.718-9.378) between groups. Subgroup analysis suggested there was no priority of endometrial preparation method in IUAs combined with thin endometrium.Conclusion: HRT with GnRH-a pretreatment improves pregnancy outcomes in women with history of IUAs. GnRH-a may restore the endometrial receptivity in the FET cycles in IUAs.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
M D C Nogale. Barrios ◽  
J A García-Velasco ◽  
M Cruz ◽  
S D Frutos ◽  
E M Martínez ◽  
...  

Abstract Study question To investigate which factors, excluding embryo aneuploidies, are associated with miscarriage in patients who have undergone a single euploid blastocyst transfer. Summary answer Miscarriage was related to the body mass index (BMI), the type of cycle and the thickness of the endometrium. What is known already Preimplantation genetic testing for aneuploidies (PGT-A) is widely used in-vitro fertilization (IVF) to select euploid embryos. Several studies have shown that embryo aneuploidy is the main contributing factor for IVF failure, reinforcing the relevance of PGT-A as a method to select chromosomally normal embryos. A recent meta-analysis confirmed that patients undergoing PGT-A have a lower miscarriage rate than women that conceived naturally (9% vs 28%, respectively). Even though most of the studies show that PGT-A significantly reduces miscarriage rate, still some women do lose their pregnancies. We investigated which other reasons may be related to this early pregnancy loss. Study design, size, duration Retrospective, observational, and multicenter study of 6910 patients undergoing single euploid blastocyst transfer after PGT-A from January 2017 to December 2019 in our institution. Several laboratory and clinic variables were analyzed to study the effect of these variables on the miscarriage rate Participants/materials, setting, methods Indications for PGT-A were advanced maternal age, implantation failure, recurrent pregnancy loss and male factor. Embryos were cultured 5% O2 concentration and 6.5% CO2 concentration. Trophectoderm biopsy was performed on day 5/6 of development and analyzed through Next Generation Sequencing (NGS); embryos were vitrified until transfer was performed. Single euploid embryo transfer was performed in all cases. We performed a multivariate regression analysis to compare the different variables and search for there are significant differences. Main results and the role of chance We studied a total of 6910 patients undergoing PGT-A to describe which factors, excluding embryo aneuploidies, were correlated with miscarriage in patients who underwent single thawed euploid embryo transfer. When considering embryo morphology (embryo grading, quality of inner cell and quality of trophectoderm), we did not find differences in miscarriage rate among groups (high quality= 15.9%; normal quality= 14.3%; low quality= 15.0%; poor quality= 14.8%) p = 0.833. BMI was significantly associated with miscarriage rate (odds ratio [OD] 1.04; 95% confidence interval [CI], 1.012–1–076 p = 0.006) and miscarriage rate. We observed a weak association between endometrial thickness and miscarriage rate ([OD] 0.65; 95%, 0.528–0.778 p = 0.04) and also between type of endometrial preparation (natural cycle or hormone replacement cycle) ([OD] 0.77; 95%, 0.528–0.778) p = 0.04. Body mass index, according to our findings, was the main variable correlated with miscarriage rate. We did not find any association with the other variables studied (biopsy day, maternal age, male age, duration infertility, cycle length, previous miscarriage, previous live birth, previous cycles IVF, endometrial pattern and diagnosis). Limitations, reasons for caution The retrospective study design limits the generalization of our results but offers a good insight to be validated in prospective trials. Wider implications of the findings: According to our findings, BMI, endometrial thickness the day of the embryo transfer, and the type of endometrial preparation should be considered when transferring an euploid blastocyst. Trial registration number NO APLICA


Author(s):  
Run-xin Gan ◽  
Yuan Li ◽  
Juan Song ◽  
Quan Wen ◽  
Guang-xiu Lu ◽  
...  

Objective: To investigate the efficacies of three cycle regimens in women receiving FET with a history of CS: natural cycle (NC) treatment, hormone replacement therapy (HRT) and treatment with gonadotropin-releasing hormone agonist (GnRH-a) + HRT). Design: Retrospective cohort study. Setting: University-affiliated center. Population: Patients (N = 6,159) with a history of CS who fulfilled the inclusion criteria were enrolled in the study from January 2014 to December 2019. Methods: Reproductive outcomes of patients in the NC (n = 4,306) versus HRT (n = 1,007) versus GnRH-a + HRT groups (n = 846) were compared. Main Outcome Measure: The main outcome measure was the live birth rate per embryo transfer (ET). Results: The unadjusted odds of the miscarriage rate of singleton pregnancies were also significantly higher in the HRT-group compared with the NC-group (25.5% versus 20.4%, respectively). After adjusting for possible confounding factors, the early miscarriage rate and the miscarriage rate of singleton pregnancies remained significantly higher in the HRT-group than the NC-group. The clinical pregnancy rates in the NC-, HRT- and GnRH-a + HRT-groups of women with a history of CS was 48.8%, 48% and 47.1%, respectively, and the live birth rates were 37%, 34.1% and 35.7%, respectively. Conclusion(s): In women undergoing FET with a history of CS, HRT for endometrial preparation was associated with a higher early miscarriage rate, albeit after statistical adjustment for confounding factors. Funding: The National Science Foundation of China (81501328). Key Words: Caesarean section, endometrial preparation, frozen embryo transfer, miscarriage


2021 ◽  
Vol 12 ◽  
Author(s):  
Jie Lan ◽  
Yaoqiu Wu ◽  
Zexuan Wu ◽  
Yingchen Wu ◽  
Rong Yang ◽  
...  

ObjectiveThis study aimed to compare the ultra-long gonadotropin-releasing hormone agonist (GnRH-a) protocol and the long GnRH-a protocol during in vitro fertilization (IVF) or intracytoplasmic sperm (ICSI) treatment on fertility outcomes in women with adenomyosis.Materials and MethodsThis study was a retrospective cohort study. From January 2011 to May 2018, a total of 371 fresh IVF/ICSI cycles were included. Among the cycles included, 237 cycles of 212 women underwent the ultra-long GnRH-a protocol, while 134 cycles of 116 women underwent the long GnRH-a protocol. The rates of implantation, clinical pregnancy per embryo transfer, live birth, and early miscarriage were estimated between the compared protocols.ResultsIn the study, the early miscarriage rate in women undergoing the ultra-long GnRH-a protocol was significantly lower than those undergoing the long GnRH-a protocol (12.0% versus 26.5%, p = 0.045), whereas the differences in the rates of biochemical pregnancy, implantation, clinical pregnancy, and live birth in women between the two groups showed no statistical significance. The pregnancy outcomes were also sub-analyzed according to the adenomyotic region (diffuse and focal). As for diffuse adenomyosis, the rates of clinical pregnancy and live birth in women undergoing the ultra-long GnRH-a protocol were significantly higher than those undergoing the long GnRH-a protocol (55.3% versus 37.9%, p = 0.025; 43.4% versus 25.9%, p = 0.019, respectively). However, pregnancy outcomes showed no difference between the two protocols in women with focal adenomyosis.ConclusionsThe ultra-long GnRH-a protocol during IVF/ICSI improves pregnancy outcomes in women with adenomyosis, especially in women with diffuse adenomyosis when compared with the long GnRH-a protocol.


2021 ◽  
Author(s):  
yanhong wu ◽  
Chang Liu ◽  
Chaochao Gong ◽  
Haitao Xi ◽  
Yanghua Fu ◽  
...  

Abstract Background:Previous studies have shown that, in young women, single blastocyst transfer can achieve satisfactory pregnancy results; however, few studies exist regarding the difference between fresh and frozen-thawed single blastocyst transfer. To provide further clinical strategies for single blastocyst transfer, the purpose of this retrospective analysis was to compare the pregnancy outcomes of young patients who received fresh or frozen-thawed single blastocyst transfer.Methods: A retrospective analysis of patients, aged ≤35 years, who underwent single blastocyst transfer was conducted from January 2018 to December 2018 in the reproductive center of the Second Affiliated Hospital of Wenzhou Medical University (Wenzhou, China). In total, 901 patients were included and were divided into two groups, based on the type of transfer cycle: the fresh embryo transfer cycle group (group A; n=693) and the frozen-thawed embryo transfer cycle group (group B; n=208). The laboratory and pregnancy outcomes were compared between the groups.Results:The number of oocytes retrieved in group B was significantly higher than in group A (P<0.05). The early miscarriage rate in group B was significantly higher than in group A and was significantly different (P<0.05). Frozen-thawed single blastocyst transplantation was an independent risk factor for early miscarriage. Other basic conditions and obstetric pregnancy outcomes were not significantly different between the two groups.Conclusions:Favourable pregnancy outcomes could be obtained with fresh and frozen-thawed single blastocyst transfer in young patients. However, because the early miscarriage rate was higher in the frozen-thawed embryo transfer group, further research is needed to determine the cause and possible solutions.


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 &gt; 10.6 ng/ml was considered as adequate and euploid FET was performed on the following day (FET Group 1). P4 &lt; 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 &gt; 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 &lt; 10.6 ng/ml) and restored values the day of FET (P4 &gt; 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.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
R. Sainte-Rose ◽  
C. Petit ◽  
L. Dijols ◽  
C. Frapsauce ◽  
F. Guerif

AbstractThe aim of this study was to determine the effectiveness of extended embryo culture in advanced maternal age (AMA) patients (37–43 years). In this retrospective analysis, 21,301 normally fertilized zygotes from 4952 couples were cultured until the blastocyst stage. Blastocyst development, including kinetics and morphology, transfer rate, implantation and live birth rates, were measured. In AMA patients, the blastocyst rate was significantly decreased as compared to that in younger women. On day 5, blastocysts underwent growth retardation in AMA patients, which was highlighted by a decreased rate of full/expanded blastocysts. Organization of the cells (trophectoderm and inner cell mass) was unaffected by age. However, in AMA patients, a ‘good’ morphology blastocyst had a decreased probability to implant compared with an ‘average’ morphology blastocyst in younger women. While the rates of blastocyst transfer and useful blastocysts were similar to younger patients, in AMA patients, both implantation and live birth rates were significantly reduced. Our results support the idea that extended embryo culture is not harmful for AMA patients. However, embryo selection allowed by such culture is not powerful enough to avoid chromosomal abnormalities in the developed blastocysts and therefore cannot compensate for the effect of a woman’s age.


Zygote ◽  
2021 ◽  
pp. 1-6
Author(s):  
Linjun Chen ◽  
Zhenyu Diao ◽  
Jie Wang ◽  
Zhipeng Xu ◽  
Ningyuan Zhang ◽  
...  

Summary This study analyzed the effects of the day of trophectoderm (TE) biopsy and blastocyst grade on clinical and neonatal outcomes. The results showed that the implantation and live birth rates of day 5 (D5) TE biopsy were significantly higher compared with those of D6 TE biopsy. The miscarriage rate of the former was lower than that of the latter, but there was no statistically significant difference. Higher quality blastocysts can achieve better implantation and live birth rates. Among good quality blastocysts, the implantation and live birth rates of D5 and D6 TE biopsy were not significantly different. Among fair quality and poor quality blastocysts, the implantation and live birth rates of D5 TE biopsy were significantly higher compared with those of D6 TE biopsy. Neither blastocyst grade nor the day of TE biopsy significantly affected the miscarriage rate. Neonatal outcomes, including newborn sex, gestational age, preterm birth, birth weight and low birth weight in the D5 and D6 TE biopsies were not significantly different. Both blastocyst grade and the day of TE biopsy must be considered at the same time when performing preimplantation genetic testing–frozen embryo transfer.


2021 ◽  
Author(s):  
Meilan Mo ◽  
Qizhen Zheng ◽  
Hongzhan Zhang ◽  
Shiru Xu ◽  
Fen Xu ◽  
...  

Abstract Objective: This retrospective study aimed to explore the optimal endometrial preparation method in women with intrauterine adhesions (IUAs).Method: A total of 882 frozen-thawed embryo transfer (FET) cycles from patients with history of IUAs were categorized into three groups based on endometrial preparation methods: hormone replacing therapy cycle (HRT, n=636), natural cycle (NC n=174), and HRT with GnRH-a pretreatment (HRT+GnRH-a, n=72. Logistic regression was performed to investigate the association between cycle regimens and pregnancy outcomes. Subgroup analysis of IUAs combined with thin endometrium (≤7mm) was also performed.Results: HRT with GnRH-a pretreatment was associated with higher incidences of clinical pregnancy, ongoing pregnancy, and live birth, but lower early miscarriage compared with either HRT or NC. Logistic regression indicated that after controlling for potential confounders, the incidences of live birth (HRT+GnRH-a as reference; NC: aOR=0.577, 95%CI 0.304-1.093; HRT: aOR=0.434, 95%CI 0.247-0.765) and ongoing pregnancy (NC: aOR=0.614, 95%CI 0.324-1.165; HRT: aOR=0.470, 95%CI 0.267-0.829) remained significantly higher in HRT+GnRH-a compared to those in HRT, but comparable to those in NC. While there was no significant difference with respect to the clinical pregnancy rate (NC: aOR=0.695, 95%CI 0.374-1.291; HRT: aOR=0.650, 95%CI 0.374-1.127) and early miscarriage rate (NC: aOR=1.734, 95%CI 0.417-7.175; HRT: aOR=2.594, 95%CI 0.718-9.378) between groups. Subgroup analysis suggested there was no superiority of endometrial preparation method in IUAs combined with thin endometrium.Conclusion: HRT with GnRH-a pretreatment improves pregnancy outcomes in women with history of IUAs. GnRH-a may restore the endometrial receptivity in the FET cycles in IUAs.


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