scholarly journals Association between serum progesterone levels on the day of frozen-thawed embryo transfer and pregnancy outcomes after artificial endometrial preparation

2020 ◽  
Author(s):  
Jing Zhu ◽  
Qianqian Zhu ◽  
Jialyu Huang ◽  
Meiting Qiu ◽  
Yanwen Zhu ◽  
...  

Abstract Background Previous studies have examined that a range of optimal serum P level during the implantation period was associated with optimal live birth rates. However, those results obtained with vaginal or intramuscular route of progesterone administration for LPS alone. Is there a relationship between the serum progesterone (P) on the day of frozen-thawed embryo transfer (FET) with the likelihood of a live birth(LB) in artificial cycles(AC) when using a combination of oral dydrogesterone and vaginal progesterone for luteal phase support (LPS)? Methods This was a retrospective study of 3659 FET cycles with artificial endometrial preparation in a Chinese tertiary-care academic medical centre from January 2015 to February 2017. Endometrial preparation was performed using estradiol (E 2 ) valerate (Fematon-red tablets) 8 mg/d beginning on day 3 of the cycle, followed by administration of P both orally (40 mg dydrogesterone and 8 mg E 2 twice per day, Fematon-yellow tablets) and vaginally (400 mg/d; Utrogestan). The primary endpoint was LBR. The association between the serum P level on the embryo transfer day and pregnancy outcomes was evaluated by univariable and multivariable logistic regression analysis. Results Mean serum P on the day of embryo transfer was 10.30 ± 3.88 ng/ml (percentiles: 25, 7.9; 50, 9.7; 75, 12.1). The LBRs according to the serum P quartiles were as follows: Q1, 35.7%; Q2, 37.4%; Q3, 39.1%; and Q4: 38.9%. Logistic regression analysis showed that the odds of a LB were not significantly different between the low (P <7.9 ng/mL) and high (P ≥7.9 ng/mL) progesterone groups before or after adjustment (crude odds ratio [OR] = 0.89, 95% confidence interval [CI]: 0.76-1.04; adjusted OR = 0.89, 95% CI: 0.75-1.04). Conclusions The present study suggests that the serum P levels on the day of ET do not correlate with the likelihood of a LB in artificial cycles when using a combination of oral dydrogesterone and vaginal progesterone for luteal phase support. In addition, prospective, randomized, controlled, blinded trials are merited to determine the optimal dosing regimen for oral dydrogesterone in in AC-FET for LPS.

2020 ◽  
Author(s):  
Jing Zhu ◽  
Qianqian Zhu ◽  
Jialyu Huang ◽  
Meiting Qiu ◽  
Yanwen Zhu ◽  
...  

Abstract The authors have withdrawn this preprint due to erroneous posting.


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.


Author(s):  
Gülşen Doğan Durdağ ◽  
Gizem Bektaş ◽  
Esengül Türkyılmaz ◽  
Halime Göktepe ◽  
Meltem Sönmezer ◽  
...  

Objective: In frozen-thawed embryo transfer (FET) cycles, preparing a synchronous endometrium for the embryo is essential. Aim of this study is to provide individualized luteal support in hormonally replaced FET cycles, and to evaluate mid-luteal serum progesterone levels and pregnancy outcomes.Study Design: In this prospective cohort study, 30 patients were included in a university hospital in six month-period. Serum progesterone level on embryo transfer day was monitored, and if it was found to be below the lower limits defined by previous studies (10 ng/mL), additional 100 mg intramuscular micronized progesterone was administered once.Mid-luteal progesterone levels and pregnancy outcomes were recorded.Results: There was no significant difference between mid-luteal progesterone levels of the patients whose transfer day progesterone was above and below 10 ng/mL (p=0.481). Although clinical pregnancy rate tended to be higher in patients whose mid-luteal progesterone was above 10 ng/mL, it was also not statistically significant.Conclusion: This is the first study in which vaginal progesterone treatment was supported by intramuscular progesterone according to serum progesterone values for the purpose of individualized progesterone support. Significant difference was not found in pregnancy outcomes. However, further studies are required to optimize management and improve pregnancy rates in hormonally treated FET cycles.


Author(s):  
Abbas Aflatoonian ◽  
Banafsheh Mohammadi

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.


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.


2020 ◽  
Vol 80 (08) ◽  
pp. 820-833
Author(s):  
Dongjia Chen ◽  
Xiaoting Shen ◽  
Yu Fu ◽  
Chenhui Ding ◽  
Yiping Zhong ◽  
...  

AbstractWhile widely used for ovulation induction in assisted reproductive technology, the clinical efficacy of letrozole for endometrial preparation prior to frozen-thawed embryo transfer (FET) cycles remains yet to be elucidated. We performed a meta-analysis to compare pregnancy outcomes after letrozole use with those of other endometrial preparation protocols in patients undergoing FET. PubMed, Scopus, Embase and the Cochrane Library were searched for eligible studies. Clinical pregnancy rate (CPR), live birth rate (LBR) and birth defect rate (BDR) were analysed using odds ratio (OR) and 95% confidence interval (CI). A total of 10 studies representing 75 968 FET cycles were included. Comparable CPR and LBR were observed when comparing letrozole administration with natural cycle (OR 1.24, 95% CI: 0.69 – 2.24; OR 1.18, 95% CI: 0.60 – 2.32), artificial cycle (OR 1.46, 95% CI: 0.87 – 2.44; OR 1.39, 95% CI: 0.77 – 2.52), and artificial cycle with gonadotropin-releasing hormone agonist suppression (OR 1.11, 95% CI: 0.78 – 1.59; OR 1.18, 95% CI: 0.82 – 1.68). Pooled results of the limited studies comparing letrozole with human menopausal gonadotropin demonstrated a similar CPR between groups (OR 1.46, 95% CI: 0.29 – 7.21, two studies), but the letrozole group had a statistically lower LBR (OR 0.67, 95% CI: 0.52 – 0.86, one study). No increased BDR was observed in the letrozole group compared to natural cycles or artificial cycles (OR 0.98, 95% CI: 0.60 – 1.61; OR 1.39, 95% CI; 0.84 – 2.28). This pooled analysis supports the use of letrozole as an efficacious and safe alternative to mainstream regimens for endometrial preparation in FET cycles.


Author(s):  
Afsoon Zareii ◽  
Sara Davoodi ◽  
Mahshid Alborzi ◽  
Marzieh Eslami Moghadam ◽  
Elham Askary

Background: Since progesterone alone does not seem to be enough for luteal phase support (LPS), especially in frozen embryo transfer (FET) cycles, so gonadotropin-releasing hormone agonist (GnRH-a) is suggested as an adjuvant therapy in combination with progesterone for LPS. Objective: To evaluate the effects of the administration of GnRH agonists with vaginal progesterone compared to vaginal progesterone alone in luteal phase support of the frozen-thawed embryo transfer cycles. Materials and Methods: In this randomized controlled clinical trial, 240 infertile women who were candidates for FET were evaluated into two groups (n = 120/each). Group I received 400 mg vaginal progesterone twice a day from the time of transfer. The second group received vaginal progesterone and also 0.1 mg diphereline on days 0, 3, and 6 of FET for LPS. Finally, the clinical and ongoing pregnancy rates, and the implantation, and spontaneous abortion rates were compared in two groups. Results: Results showed that there was no significant difference between the mean age of women and the duration of infertility (p = 0.78, p = 0.58, respectively). There were no significant differences between groups in the terms of implantation and spontaneous abortion rates (p = 0.19, p = 0.31, respectively). However, in terms of clinical and ongoing pregnancy rates, the significant differences were seen between groups (p = 0.008 and p = 0.005, respectively). Conclusion: Co-administration of GnRH-a and vaginal progesterone in LPS may be superior to vaginal progesterone alone in women who underwent a frozen-selected embryo transfer cycle. Key words: Luteal phase, Fertilization in vitro, Embryo transfer.


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