scholarly journals Effects of immediate versus delayed frozen embryo transfer in high responder patients undergoing freeze-all cycles

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Na Zuo ◽  
Yingzhuo Gao ◽  
Ningning Zhang ◽  
Da Li ◽  
Xiuxia Wang

Abstract Background Frozen embryo transfer (FET) can greatly improve the pregnancy outcomes for high responder patients. However, it is not known whether the timing of FET is a risk factor on pregnancy outcomes in high responder patients undergoing freeze-all cycles. Methods A retrospective cohort study to compare the pregnancy outcomes of the immediate and delayed FET groups in high responder patients undergoing freeze-all cycles. The two groups were defined as that FET took place either within the first menstrual cycle following oocyte retrieval or afterwards. Propensity score matching was used to make the potential risk factors of the two groups comparable. Multivariable regression analysis was used to study the effect of the timing of FET on pregnancy outcomes in the entire cohort and propensity score-matched cohort, even in different controlled ovarian hyperstimulation protocol cohorts as subgroup analysis. Results We obtained 1130 patients in immediate FET group and 998 patients in delayed FET group, and the average age of the two groups were 30.30 and 30.63. We showed that the immediate FET group were equivalent to delayed FET group in the entire cohort [clinical pregnancy rate (CPR), 61.0% versus 63.4%, adjusted odd ratio (OR), 0.939, 95% confidence interval (CI), 0.781–1.129; spontaneous abortion rate (SAR), 10.1% versus 12.6%, adjusted OR, 0.831, 95% Cl (0.628–1.098); live birth rate (LBR), 49.9% versus 49.2%, adjusted OR, 1.056, 95% Cl (0.883–1.263)]. The same results were obtained by χ2 test in the propensity score-matched cohort (CPR, 60.5% versus 63.5%; SAR, 11.6% versus 12.3%; LBR, 48% versus 49.3%) (P > 0.05). Subgroup analysis indicated that pregnancy outcomes of immediate FET were no difference to delayed FET in gonadotropin-releasing hormone agonist (GnRH-a) protocol (P > 0.05). The SAR of the immediate FET group were lower than that of the delayed FET group in GnRH antagonist protocol (adjusted OR, 0.645, 95% CI, 0.430–0.966) (P < 0.05), no differences were observed in CPR and LBR (P > 0.05). Conclusions The pregnancy outcomes of immediate FET were no difference to delayed FET in high responder population undergoing freeze-all cycles.

2020 ◽  
Author(s):  
Na Zuo ◽  
Yingzhuo Gao ◽  
Ningning Zhang ◽  
Da Li ◽  
Xiuxia Wang

Abstract Background: Frozen embryo transfer (FET) can greatly improve the pregnancy outcomes for high ovarian response (HOR) population. However, it is not known whether the impaired endometrial receptivity derived from controlled ovarian hyperstimulation (COH) can be fully recovered in the first menstrual cycle after oocyte retrieval, and whether the timing of FET is a risk factor on pregnancy outcomes in HOR population undergoing freeze-all strategy.Methods: A retrospective cohort study to compare the pregnancy outcomes of the immediate and delayed FET groups in HOR population undergoing freeze-all strategy. Propensity score matching was used to make the potential risk factors of the immediate and delayed FET groups comparable. Multivariable regression analysis was used to study the effect of the timing of FET on pregnancy outcomes in the entire cohort and propensity score-matched cohort, even in different COH protocol cohorts as subgroup analysis.Results: We showed that the immediate FET group were no worse than delayed FET group in the entire cohort [clinical pregnancy rate (CPR), adjusted odd ratio (OR), 0.942, 95% confidence interval (CI), 0.784-1.133; spontaneous abortion rate (SAR), adjusted OR, 1.118, 95% Cl (0.771-1.623); live birth rate (LBR), adjusted OR, 1.060, 95% Cl (0.886-1.267)]. The same results were obtained by χ2 test in the propensity score-matched cohort (CPR, 60.5% versus 63.5%; SAR, 11.6% versus 12.3%; LBR, 48% versus 49.3%) (P > 0.05). Subgroup analysis indicated that pregnancy outcomes of immediate FET were non-inferior to delayed FET in short-acting gonadotropin-releasing hormone agonist (GnRH-a) long protocol (P > 0.05). The SAR of the immediate FET group were lower than that of the delayed FET group in GnRH antagonist protocol (adjusted OR, 0.646, 95% CI, 0.432-0.966) and long-acting GnRH-a long protocol (adjusted OR, 0.375, 95% CI, 0.142-0.990) (P < 0.05), no differences were observed in CPR and LBR (P > 0.05).Conclusions: These findings indicate that immediate FET might not affect pregnancy outcomes in HOR patients undergoing freeze-all strategy. Delaying FET could increase the SAR in GnRH-ant and long-acting GnRH-a long protocols.


2020 ◽  
Vol 35 (7) ◽  
pp. 1630-1636 ◽  
Author(s):  
Phillip A Romanski ◽  
Pietro Bortoletto ◽  
Zev Rosenwaks ◽  
Glenn L Schattman

Abstract STUDY QUESTION Will a delay in initiating IVF treatment affect pregnancy outcomes in infertile women with diminished ovarian reserve? SUMMARY ANSWER A delay in IVF treatment up to 180 days does not affect the live birth rate for women with diminished ovarian reserve when compared to women who initiate IVF treatment within 90 days of presentation. WHAT IS KNOWN ALREADY In clinical practice, treatment delays can occur due to medical, logistical or financial reasons. Over a period of years, a gradual decline in ovarian reserve occurs which can result in declining outcomes in response to IVF treatment over time. There is disagreement among reproductive endocrinologists about whether delaying IVF treatment for a few months can negatively affect patient outcomes. STUDY DESIGN, SIZE, DURATION A retrospective cohort study of infertile patients in an academic hospital setting with diminished ovarian reserve who started an IVF cycle within 180 days of their initial consultation and underwent an oocyte retrieval with planned fresh embryo transfer between 1 January 2012 and 31 December 2018. PARTICIPANTS/MATERIALS, SETTING, METHODS Diminished ovarian reserve was defined as an anti-Müllerian hormone (AMH) &lt;1.1 ng/ml. In total, 1790 patients met inclusion criteria (1115 immediate and 675 delayed treatment). Each patient had one included cycle and no subsequent data from additional frozen embryo transfer cycles were included. Since all cycle outcomes evaluated were from fresh embryo transfers, no genetically tested embryos were included. Patients were grouped by whether their cycle started 1–90 days after presentation (immediate) or 91–180 days (delayed). The primary outcome was live birth (≥24 weeks of gestation). A subgroup analysis of more severe forms of diminished ovarian reserve was performed to evaluate outcomes for patients with an AMH &lt;0.5 and for patients &gt;40 years old with an AMH &lt;1.1 ng/ml (Bologna criteria for diminished ovarian reserve). Logistic regression analysis, adjusted a priori for patient age, was used to estimate the odds ratio (OR) with a 95% CI. All pregnancy outcomes were additionally adjusted for the number of embryos transferred. MAIN RESULTS AND THE ROLE OF CHANCE The mean ± SD number of days from presentation to IVF start was 50.5 ± 21.9 (immediate) and 128.8 ± 25.9 (delayed). After embryo transfer, the live birth rate was similar between groups (immediate: 23.9%; delayed: 25.6%; OR 1.08, 95% CI 0.85–1.38). Additionally, a similar live birth rate was observed in a subgroup analysis of patients with an AMH &lt;0.5 ng/ml (immediate: 18.8%; delayed: 19.1%; OR 0.99, 95% CI 0.65–1.51) and in patients &gt;40 years old with an AMH &lt;1.1 ng/ml (immediate: 12.3%; delayed: 14.7%; OR 1.21, 95% CI 0.77–1.91). LIMITATIONS, REASONS FOR CAUTION There is the potential for selection bias with regard to the patients who started their IVF cycle within 90 days compared to 91–180 days after initial consultation. In addition, we did not include patients who were seen for initial evaluation but did not progress to IVF treatment with oocyte retrieval; therefore, our results should only be applied to patients with diminished ovarian reserve who complete an IVF cycle. Finally, since we excluded patients who started their IVF cycle greater than 180 days from their first visit, it is not known how such a delay in treatment affects pregnancy outcomes in IVF cycles. WIDER IMPLICATIONS OF THE FINDINGS A delay in initiating IVF treatment in patients with diminished ovarian reserve up to 180 days from the initial visit does not affect pregnancy outcomes. This observation remains true for patients who are in the high-risk categories for poor response to ovarian stimulation. Providers and patients should be reassured that when a short-term treatment delay is deemed necessary for medical, logistic or financial reasons, treatment outcomes will not be affected. STUDY FUNDING/COMPETING INTEREST(S) No financial support, funding or services were obtained for this study. The authors do not report any potential conflicts of interest. TRIAL REGISTRATION NUMBER Not applicable.


Author(s):  
Nathalie F. Wang ◽  
Leif Bungum ◽  
Sven O. Skouby

Abstract The need for luteal phase support in IVF/ICSI is well established. A large effort has been made in the attempt to identify the optimal type, start, route, dosage and duration of luteal phase support for IVF/ICSI and frozen embryo transfer. These questions are further complicated by the different types of stimulation protocols and ovulation triggers used in ART. The aim of this review is to supply a comprehensive overview of the available types of luteal phase support, and the indications for their use. A review of the literature was carried out in the effort to find the optimal luteal phase support regimen with regards to pregnancy related outcomes and short and long term safety. The results demonstrate that vaginal, intramuscular, subcutaneous and rectal progesterone are equally effective as luteal phase support in IVF/ICSI. GnRH agonists and oral dydrogesterone are new and promising treatment modalities but more research is needed. hCG and estradiol are not recommended for luteal phase support. More research is needed to establish the most optimal luteal phase support in frozen embryo transfer cycles, but progesterone has been shown to improve live birth rate in some studies. Luteal phase support should be commenced between the evening of the day of oocyte retrieval, and day three after oocyte retrieval and it should be continued at least until the day of positive pregnancy test. So, in conclusion still more large and well-designed RCT’s are needed to establish the most optimal luteal phase support in each stimulation protocol, and especially in frozen embryo transfer.


2021 ◽  
Vol 6 (1) ◽  

To date, there is no consensus in embryo developmental stages for cryopreservation. The present study aimed to investigate the impact of embryo developmental stages at cryopreservation on pregnancy outcomes of frozen embryo transfer. Systematic review and meta-analysis of relevant studies identified through MEDLINE literature search was performed. The primary outcome was live birth/delivery rate, and the secondary outcomes included implantation rate, ongoing pregnancy rate, clinical pregnancy rate, miscarriage rate, and multiple pregnancy rate. The protocol of this systematic review has been registered on PROSPERO 2017 (registration number: CRD42017072828). Five studies met the eligibility criteria were included in the present review. The outcomes of embryos frozen at different stages but transferred at the same stage were analyzed and compared. Embryos frozen at non-blastocyst showed a significant higher delivery/live birth rate than those cryopreserved at blastocyst (odds ratio=1.37; 95% confidence interval, 1.13-1.66) in the setting of frozen embryo transfer with blastocysts. There was only a limited number of studies with analyzable data for comparisons. The literature varied substantially in study design and methodology applied. Although a significant difference was observed toward an improved delivery/live birth rate for blastocyst transfer with embryos frozen at non-blastocyst stage, future studies are required to further corroborate this finding.


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Jiaqi Yang ◽  
Yichen He ◽  
Yiqing Wu ◽  
Dan Zhang ◽  
Hefeng Huang

Abstract Background There has been increasing interest in the relationship between body mass index(BMI) and pregnancy outcomes, especially in women undergoing frozen embryo transfer(FET). Several observational studies have been published, but so far with conflicting results. Methods A systematic review and meta-analysis was conducted according to PRISMA guidelines. Pubmed, Embase, Cochrane Library, Clinicaltrails.gov and Web of Science databases were searched based on established search strategy from inception through January 2021. Results Twelve studies were eligible. In women following FET, high BMI (BMI ≥ 23 kg/m2) was associated with an impaired live birth rate (LBR, OR: 0.89, 95% CI: 0.82–0.96, P = 0.002), but wasn’t associated with the implantation rate or the clinical pregnancy rate. Subgroup analysis revealed higher LBR for women didn’t complicated by polycystic ovary syndrome (PCOS, OR: 0.96, 95% CI: 0.85–1.08, P = 0.46) and women with blastocyst transferred (OR: 0.89, 95% CI: 0.68–1.16, P = 0.40). LBR did not differ between the low BMI group (BMI < 18.5 kg/m2) and the normal weight group. Conclusions Our study showed that high BMI in women is negatively associated with LBR in FET cycles, whereas low BMI isn’t. The results of subgroup analysis implied a need for women with a high BMI to get individualized weight management and treatment. Further evidence is still required to optimize preconception health and develop Nutritional and exercise guidelines.


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.


BMJ Open ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. e042395
Author(s):  
Simone Cornelisse ◽  
Liliana Ramos ◽  
Brigitte Arends ◽  
Janneke J Brink-van der Vlugt ◽  
Jan Peter de Bruin ◽  
...  

IntroductionIn vitro fertilisation (IVF) has evolved as an intervention of choice to help couples with infertility to conceive. In the last decade, a strategy change in the day of embryo transfer has been developed. Many IVF centres choose nowadays to transfer at later stages of embryo development, for example, transferring embryos at blastocyst stage instead of cleavage stage. However, it still is not known which embryo transfer policy in IVF is more efficient in terms of cumulative live birth rate (cLBR), following a fresh and the subsequent frozen–thawed transfers after one oocyte retrieval. Furthermore, studies reporting on obstetric and neonatal outcomes from both transfer policies are limited.Methods and analysisWe have set up a multicentre randomised superiority trial in the Netherlands, named the Three or Fivetrial. We plan to include 1200 women with an indication for IVF with at least four embryos available on day 2 after the oocyte retrieval. Women are randomly allocated to either (1) control group: embryo transfer on day 3 and cryopreservation of supernumerary good-quality embryos on day 3 or 4, or (2) intervention group: embryo transfer on day 5 and cryopreservation of supernumerary good-quality embryos on day 5 or 6. The primary outcome is the cLBR per oocyte retrieval. Secondary outcomes include LBR following fresh transfer, multiple pregnancy rate and time until pregnancy leading a live birth. We will also assess the obstetric and neonatal outcomes, costs and patients’ treatment burden.Ethics and disseminationThe study protocol has been approved by the Central Committee on Research involving Human Subjects in the Netherlands in June 2018 (CCMO NL 64060.000.18). The results of this trial will be submitted for publication in international peer-reviewed and in open access journals.Trial registration numberNetherlands Trial Register (NL 6857).


F&S Reports ◽  
2021 ◽  
Author(s):  
Wendy Y. Zhang ◽  
Rebecca M. Gardner ◽  
Kristopher I. Kapphahn ◽  
Maya K. Ramachandran ◽  
Gayathree Murugappan ◽  
...  

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.


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