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

Zarei, Afsoon; Sohail, Parastoo; Parsanezhad, Mohammad Ebrahim; Alborzi, Saeed; Samsami, Alamtaj; Kutenaee, Maryam Azizi

doi:10.1007/s00404-016-4217-4

Cited by 60 publications

(60 citation statements)

References 27 publications

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“…From our study, we showed that large spanned serum P level induced by different progesterone regimen did not impact live birth rate in HRT-FET cycles. Similar results showed that progesterone vaginally administered resulted comparable results with intramuscular regimen as luteal support in fresh IVF cycles [18][19][20]. We further analyzed neonatal outcomes stratified by different progesterone regimen and found no significant difference of infant birthweight, preterm delivery rate, SGA and LGA rate.…”

Section: Discussionsupporting

confidence: 64%

Progesterone regimen impact on live birth rate and neonatal outcomes in artificial frozen-thawed embryo transfer cycles: a retrospective cohort study

Liu¹,

Wu²

2020

Preprint

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Background: Previous studies have demonstrated that singletons from frozen embryo transfer (FET) are heavier and longer-gestational-days at delivery than those from fresh embryo transfer. The amounts and routes of progesterone used in FET vary tremendously among different ART centers.Does different serum progesterone level induced by different progesterone regimens determine live birth rate and neonatal outcomes in hormone replacement therapy frozen-thawed embryo transfer (HRT-FET) cycles?Design: A cohort study of 856 HRT-FET cycles from a Chinese public fertility center. Data from patients undergoing their first FET cycles from 2015-2018 were extracted from the database. All patients had their first FET with two day2 or day3 embryos transferred. Endometrial preparation was performed with sequential administration of estrogen followed by progesterone 60mg per day intramuscularly or Crinone 90mg per day vaginally. Live birth was the primary outcome. Secondary outcome included clinical pregnancy rate, singleton birthweight, large for gestational age (LGA) rate, SGA rate and preterm delivery rate. Student's t test, Mann-Whitney U-test, Chi square analysis and multivariable logistic regression were used where appropriate. Differences were considered significant if p<0.05.Results: No significant difference of live birth rate was found between different progesterone regimens (Adjusted OR 1.128, 95%CI 0.842, 1.511, p=0.420). Neonatal outcomes like birthweight, preterm delivery rate, SGA and LGA rate were not different between two progesterone regimens.Serum P level >41.82 pmol/L at 14 day post-FET was associated with higher live birth rate than serum P level ≤41.82pmolL in HRT-FET cycles when progesterone was intramuscularly delivered (Adjusted OR 1.690, 95%CI 1.002, 2.849, p=0.049). Birthweight and gestational weeks were not different between these two different P level groups. Conclusions: Progesterone vaginally or intramuscularly didn't impact live birth rate and neonatal outcomes in artificial FET cycles. Relatively higher serum progesterone level induced by intramuscular regimen did not increase newborn birthweight or prolong gestational weeks compared to vaginal regimen. Intramuscular progesterone supplementation during HRT-FET cycles was associated with development in cows. Theriogenology 2011, 76:1594-1601. 17. Nogueira MF, Melo DS, Carvalho LM, Fuck EJ, Trinca LA, Barros CM: Do high progesterone concentrations decrease pregnancy rates in embryo recipients synchronized with PGF2alpha and eCG? Theriogenology 2004, 61:1283-1290. 18. Mitwally MF, Diamond MP, Abuzeid M: Vaginal micronized progesterone versus intramuscular progesterone for luteal support in women undergoing in vitro fertilization-embryo transfer. Fertil Steril 2010, 93:554-569. 19. Zarei A, Sohail P, Parsanezhad ME, Alborzi S, Samsami A, Azizi M: Comparison of four protocols for luteal phase support in frozen-thawed Embryo transfer progesterone on the day of embryo transfer is associated with a diminished ongoing pregnancy rate in oocyte donation ...

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Section: Discussionsupporting

confidence: 64%

Progesterone regimen impact on live birth rate and neonatal outcomes in artificial frozen-thawed embryo transfer cycles: a retrospective cohort study

Liu¹,

Wu²

2020

Preprint

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“…Ten studies were further examined for eligibility: one study was excluded because it compared dydrogesterone with vaginal progesterone capsules for luteal support in IUI cycles ( Khosravi et al ., 2015 ). Nine studies were included in our quantitative analysis ( Chakravarty et al ., 2005a ; Ganesh et al ., 2011 ; Patki & Pawar, 2007 ; Rashidi et al ., 2016 ; Saharkhiz et al ., 2016 ; Salehpour et al ., 2013 ; Tournaye et al ., 2017 ; Zarei et al ., 2017 ; Zargar et al ., 2016 ); four of the nine studies had groups given medication other than oral dydrogesterone and vaginal progesterone capsules: vaginal progesterone gel ( Ganesh et al ., 2011 ); intramuscular progesterone ( Rashidi et al ., 2016 ; Zargar et al ., 2016 ); dydrogesterone combined with either GnRH agonist or hCG ( Zarei et al ., 2017 ). The individuals in these groups were not included in the quantitative analysis.…”

Section: Resultsmentioning

confidence: 99%

Oral dydrogesterone vs. vaginal progesterone capsules for luteal-phase support in women undergoing embryo transfer: a systematic review and meta-analysis

Mwp¹,

Npb²,

Acp³

et al. 2018

JBRA Assisted Reproduction

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ObjectiveTo identify, appraise, and summarize the evidence from randomized controlled trials (RCTs) comparing oral dydrogesterone to vaginal progesterone capsules for luteal-phase support (LPS) in women offered fresh or frozen embryo transfers following in vitro fertilization.MethodsTwo independent authors screened the literature for papers based on titles and abstracts, then selected the studies, extracted data, and assessed the risk of bias. Dydrogesterone and progesterone were compared based on risk ratios (RR) and the precision of the estimates was assessed through the 95% confidence interval (CI).ResultsAn electronic search performed on June 7, 2017 retrieved 376 records, nine of which were papers deemed eligible and included in this systematic review and quantitative analysis. Good quality evidence indicates that oral dydrogesterone provided at least similar results than vaginal progesterone capsules on live birth/ongoing pregnancy (RR=1.08, 95%CI=0.92-1.26, I2=29%, 8 RCTs, 3,386 women) and clinical pregnancy rates (RR 1.10, 95% CI 0.95 to 1.27; I2=43%; 9 RCTs; 4,061 women). Additionally, moderate quality evidence suggests there is no relevant difference on miscarriage rates (RR=0.92, 95%CI=0.68-1.26, I2=6%, 8 RCTs, 988 clinical pregnancies; the quality of the evidence was downgraded because of imprecision).ConclusionsGood quality evidence from RCTs suggest that oral dydrogesterone provides at least similar reproductive outcomes than vaginal progesterone capsules when used for LPS in women undergoing embryo transfers. Dydrogesterone is a reasonable option and the choice of either of the medications should be based on cost and side effects.

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“…In this study, we used dydrogesterone, which is an orally administered synthetic progestogen that has been successfully used for luteal phase support in stimulated IVF cycles over the past decade [22-24, 37, 38]. However, limited data are available about its use in artificial frozen-thawed cycles, which have different underlying endocrinological issues [39,40]. Due to its unique molecular structure, dydrogesterone has a more selective binding capacity to the natural progesterone receptor.…”

Section: Discussionmentioning

confidence: 99%

“…However, whether only 40 mg dydrogesterone is adequate in AC-FET for LPS remains to be determined. Although two small clinical studies have investigated the use of 30 or 40 mg oral dydrogesterone for luteal phase support in programmed frozen-thawed cycles [40,42], there is also lack of randomized controlled trials at least at the national level for determining the required dose for oral dydrogesterone. Our luteal phase support protocol reduces the vaginal dose to a level that is more comfortable for patients, also ensures progesterone support for patients with poor vaginal absorption.…”

Section: Discussionmentioning

confidence: 99%

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

Zhu

Huang

et al. 2020

Preprint

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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.

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

Abstract: Vaginal progesterone provides appropriate LPS. Yet, combination of oral dydrogesterone and GnRH-α or hCG can be more suitable option compared to vaginal progesterone for LPS in women with vaginal irritation or discharge at a lower cost.

Cited by 60 publications

References 27 publications

Progesterone regimen impact on live birth rate and neonatal outcomes in artificial frozen-thawed embryo transfer cycles: a retrospective cohort study

Progesterone regimen impact on live birth rate and neonatal outcomes in artificial frozen-thawed embryo transfer cycles: a retrospective cohort study

Oral dydrogesterone vs. vaginal progesterone capsules for luteal-phase support in women undergoing embryo transfer: a systematic review and meta-analysis

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

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