Chapter-18 Natural Cycle and Endometrial Preparation Protocols for Frozen Embryo Transfer

2011 ◽  
pp. 114-121
Author(s):  
Julio Voget
Keyword(s):  
Embryo Transfer ◽  
Frozen Embryo Transfer ◽  
Natural Cycle ◽  
Endometrial Preparation

scholarly journals Nomogram to Predict an Endometrial Thickness >7.5 mm in the Frozen Embryo Transfer Cycle for Thin Endometrial Women

2021 ◽  
Author(s):  
Zizhen Guo ◽  
Wei Chen ◽  
Yuqing Wang ◽  
Ran Chu ◽  
Xinxin Xu ◽  
...  
Keyword(s):  
Embryo Transfer ◽  
Ovarian Stimulation ◽  
Endometrial Thickness ◽  
Frozen Embryo Transfer ◽  
Natural Cycle ◽  
Stimulation Protocol ◽  
Final Model ◽  
Thin Endometrium ◽  
Endometrial Preparation ◽  
Hcg Trigger

Abstract Background A sufficient endometrial thickness (EMT) is essential for successful pregnancy. For patients with a thin endometrium (EMT ≤7.5 mm on human chorionic gonadotropin [HCG] trigger day) in IVF, some studies have suggested freezing all embryos and preparing the endometrium in the subsequent frozen-thawed cycle, but not all patients can obtain a thicker endometrium during endometrial preparation in the frozen embryo transfer cycle than on HCG trigger day in the fresh embryo transfer cycle. This study aimed to investigate which characteristics of patients with a thin endometrium suggest the possibility of EMT >7.5 mm in the subsequent frozen cycle, and build up a prediction nomogram.Methods Data were collected from the university-based reproductive medical center between January 2013 and September 2019. Multivariable logistic regression was used to generate the final prediction model and construct the nomogram. Model performances were quantified by discrimination and calibration.Results The predictive variables that entered the final model were: hysteroscopic adhesiolysis history, PCOS status, application of clomiphene in the ovarian stimulation process, the ovarian stimulation protocol, and the endometrial preparation protocol. The receiver operating characteristic curve for the final model and validation cohort was 0.76 (95% confidence interval [CI]: 0.722–0.797) and 0.71 (95% CI: 0.66–0.76), respectively. Discrimination performed well in both the modeling and validation cohorts.Conclusion We conclude that in women with a thin endometrium (EMT ≤7.5 mm on HCG trigger day), the absence of a hysteroscopic adhesiolysis history, and the presence of PCOS, the application of clomiphene in the ovarian stimulation process, the application of a GnRH agonist short protocol, mild stimulation protocol, natural cycle protocol, and natural cycle for endometrial preparation are prognostic for an increased possibility of EMT >7.5 mm in the subsequent frozen cycle.

Low progesterone levels on the day before natural cycle frozen embryo transfer are negatively associated with live birth rates

2020 ◽  
Vol 35 (7) ◽  
pp. 1623-1629
Author(s):  
Sofia Gaggiotti-Marre ◽  
Manuel Álvarez ◽  
Iñaki González-Foruria ◽  
Mònica Parriego ◽  
Sandra Garcia ◽  
...  
Keyword(s):  
Corpus Luteum ◽  
Embryo Transfer ◽  
Live Birth ◽  
Luteal Phase ◽  
Frozen Embryo Transfer ◽  
Natural Cycle ◽  
Reproductive Outcomes ◽  
Endometrial Preparation ◽  
Urine Testing ◽  
The Impact

Abstract STUDY QUESTION Are progesterone (P) levels on the day before natural cycle frozen embryo transfer (NC-FET) associated with live birth rate (LBR)? SUMMARY ANSWER Regular ovulatory women undergoing NC-FET with serum P levels <10 ng/ml on the day before blastocyst transfer have a significantly lower LBR than those with serum P levels >10 ng/ml. WHAT IS KNOWN ALREADY The importance of serum P levels around the time of embryo transfer in patients undergoing FET under artificial endometrial preparation has been well established. However, no study has analyzed the importance of serum P levels in patients undergoing FET under a true natural endometrial preparation cycle. STUDY DESIGN, SIZE, DURATION This was a retrospective cohort study including 294 frozen blastocyst transfers under natural cycle endometrial preparation at a university-affiliated fertility centre between January 2016 and January 2019. PARTICIPANTS/MATERIALS, SETTING, METHODS All patients had regular menstrual cycles and underwent NC-FET with their own oocytes. Only patients who had undergone serum P measurement between 8 am and 11 am on the day before FET were included. Patients did not receive any external medication for endometrial preparation or luteal phase support. Patients were divided into two groups according to serum P levels below or above 10 ng/ml on the day before FET. Univariate analysis was carried out to describe and compare the cycle characteristics with reproductive outcomes. To evaluate the effect of P, a multivariable logistic model was fitted for each outcome after adjusting for confounding variables. MAIN RESULTS AND THE ROLE OF CHANCE Mean serum P levels on the day before FET were significantly higher in patients who had a live birth compared to those who did not (14.5 ± 7.0 vs 12.0 ± 6.6 ng/ml, 95% CI [0.83; 4.12]). The overall clinical pregnancy rate (CPR) and LBR were 42.9% and 35.4%, respectively. Patients in the higher P group (>10 ng/ml) had a higher LBR (41.1% vs 25.7%: risk difference (RD) 15.4%, 95% CI [5; 26]) and CPR (48.6% vs 33.0%: RD 15.6%, 95% CI [4; 27]). Patients with higher serum P levels on the day before FET (63% of patients) had an improved LBR (odds ratio: 1.05; 95% CI [1.02; 1.09]). Women with serum P levels <10 ng/ml on the day before FET (37% of patients) had significantly higher weights (62.5 ± 9.9 vs 58.1 ± 7.1 kg, 95% CI [1.92; 6.90]) and BMI (22.9 ± 3.6 vs 21.6 ± 2.7 kg/m2, 95% CI [0.42; 2.25]) compared to patients with P levels >10 ng/ml. LIMITATIONS, REASONS FOR CAUTION The main limitation of our study is its retrospective design. Other potential limitations are the detection of LH surge through urine testing and the inclusion of patients who did and did not undergo preimplantation genetic testing for aneuploidies. The protocol used in our institution for monitoring NC-FET does not look for the onset of progesterone secretion by the corpus luteum, and a slow luteinisation process or delay of corpus luteum function cannot be ruled out. WIDER IMPLICATIONS OF THE FINDINGS We provide evidence that a minimum serum P threshold (P >10 ng/ml) might be required for improved reproductive outcomes in NC-FET. This result suggests that there are different mechanisms by which P is produced and/or distributed by each patient. This study also provides an excellent model to evaluate the impact of luteal phase defect through NC-FET. A prospective evaluation to assess whether P supplementation should be individualised according to patient’s needs is necessary to support our findings. STUDY FUNDING/COMPETING INTEREST(S) No external funding was used, and there are no competing interests.

Effects of different cycle regimens for frozen embryo transfer on perinatal outcomes of singletons

2020 ◽  
Vol 35 (7) ◽  
pp. 1612-1622 ◽  
Author(s):  
Bian Wang ◽  
Jie Zhang ◽  
Qianqian Zhu ◽  
Xiaoyan Yang ◽  
Yun Wang
Keyword(s):  
Preterm Delivery ◽  
Embryo Transfer ◽  
Gestational Age ◽  
Low Birthweight ◽  
Perinatal Outcomes ◽  
Frozen Embryo Transfer ◽  
Natural Cycle ◽  
Z Score ◽  
Endometrial Preparation ◽  
Artificial Cycle

Abstract STUDY QUESTION Does the endometrial preparation protocol for frozen embryo transfer (FET) have an impact on perinatal outcomes? SUMMARY ANSWER Singleton newborns from conceptions after an artificial FET cycle had a higher risk of being large for gestational age (LGA). WHAT IS KNOWN ALREADY Most previous studies have concentrated on the clinical pregnancy, miscarriage and live birth rates of different endometrial preparation protocols for FET. However, the impacts of these cycle regimens on perinatal outcomes including birthweight, gestational age (GA) and related outcomes require more investigation. STUDY DESIGN, SIZE, DURATION We retrospectively analysed all singletons conceived by women who underwent non-donor FET cycles between July 2014 and July 2017. The propensity score matching (PSM) method using nearest neighbour matching at a proportion of 1:1 was established to adjust for factors that influence the probability of receiving different FET cycle regimens. The main outcomes of the study included birthweight and its related outcomes, Z-score, low birthweight (LBW, <2500 g), small for gestational age (SGA, ≤10th percentile of referential birthweight), LGA (≥90th percentile of referential birthweight) and macrosomia (birthweight >4000 g). The study outcomes also included GA at birth, preterm delivery (<37 weeks), very preterm delivery (<32 weeks), very low birthweight (VLBW, <1500 g), term LBW (at 37 weeks of gestation or greater) and preterm LBW (at <37 weeks of gestation). PARTICIPANTS/MATERIALS, SETTING, METHODS A total of 9267 cycles with live-born singletons were included in the analysis in our centre between July 2014 and July 2017. Of these, 2224, 4299 and 2744 live-born singletons were conceived by natural cycle FET, stimulated cycle FET and artificial cycle FET, respectively. After PSM, 1947 cycles of natural cycle FET versus stimulated cycle FET, 1682 cycles of stimulated cycle FET versus artificial cycle FET and 2333 cycles of natural cycle FET versus artificial cycle FET were included in the analysis. MAIN RESULTS AND THE ROLE OF CHANCE A higher mean birthweight and Z-score were observed in the artificial cycle FET group than in the stimulated cycle FET group (P = 0.005; P = 0.004, respectively). Singleton newborns conceived after artificial cycle FET were more likely to be LGA than those born after natural cycle FET or stimulated cycle FET (19.92% versus 16.94% and 19.29% versus 16.12%, respectively). The adjusted ORs (95% CIs) were 1.25 (1.05, 1.49) for artificial cycle FET compared with natural cycle FET (P = 0.014) and 1.26 (1.08, 1.46) for artificial cycle FET compared with stimulated cycle FET (P = 0.003). Newborns conceived after stimulated cycle FET had a lower mean GA at birth and a lower mean birthweight than those born after natural cycle FET or artificial cycle FET. The stimulated cycle FET group had lower adjusted odds of being macrosomia than the natural cycle FET group. No significant differences between natural cycle FET and stimulated cycle FET were found for any of the other outcomes. LIMITATIONS, REASONS FOR CAUTION This study had the disadvantage of being retrospective, and some cases were excluded due to missing data. The original allocation process was not randomized, which may have introduced bias. We have chosen not to account for multiple comparisons in our statistical analysis. WIDER IMPLICATIONS OF THE FINDINGS LGA can have long-term consequences in terms of risk for disease, which means that the influences of artificial cycle FET are of clinical significance and deserve more attention. Furthermore, these findings are critical for clinicians to be able to make an informed decision when choosing an endometrial preparation method. STUDY FUNDING/COMPETING INTEREST(S) This work was supported by grants from the National Natural Science Foundation of China (NSFC) (31770989 to Y.W.) and the Shanghai Ninth People’s Hospital Foundation of China (JYLJ030 to Y.W.). None of the authors have any conflicts of interest to declare.

Individualised luteal phase support in artificially prepared frozen embryo transfer cycles based on serum progesterone levels: a prospective cohort study

2021 ◽  
Author(s):  
Manuel Álvarez ◽  
Sofía Gaggiotti-Marre ◽  
Francisca Martínez ◽  
Lluc Coll ◽  
Sandra García ◽  
...  
Keyword(s):  
Pregnancy Rate ◽  
Embryo Transfer ◽  
Pregnancy Outcomes ◽  
Luteal Phase ◽  
Frozen Embryo Transfer ◽  
Ongoing Pregnancy ◽  
Serum Progesterone ◽  
Endometrial Preparation ◽  
Group 2 ◽  
Group 1

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.

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