Background: Progesterone prepares the endometrium for pregnancy by stimulating proliferation in response to human chorionic gonadotropin (hCG), which is produced by the corpus luteum. This occurs in the luteal phase of the menstrual cycle. In assisted reproduction techniques (ART) the progesterone or hCG levels, or both, are low and the natural process is insufficient, so the luteal phase is supported with either progesterone, hCG or gonadotropin releasing hormone (GnRH) agonists. Luteal phase support improves implantation rate and thus pregnancy rates but the ideal method is still unclear. This is an update of a Cochrane Review published in 2004 (Daya 2004).
Objectives: To determine the relative effectiveness and safety of methods of luteal phase support in subfertile women undergoing assisted reproductive technology.
Search Strategy: We searched the Cochrane Menstrual Disorders and Subfertility Group (MDSG) Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, PsycINFO, CINAHL, Database of Abstracts of Reviews of Effects (DARE), LILACS, conference abstracts on the ISI Web of Knowledge, OpenSigle for grey literature from Europe, and ongoing clinical trials registered online. The final search was in February 2011.
Selection Criteria: Randomised controlled trials of luteal phase support in ART investigating progesterone, hCG or GnRH agonist supplementation in in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI) cycles. Quasi-randomised trials and trials using frozen transfers or donor oocyte cycles were excluded.
Data Collection And Analysis: We extracted data per women and three review authors independently assessed risk of bias. We contacted the original authors when data were missing or the risk of bias was unclear. We entered all data in six different comparisons. We calculated the Peto odds ratio (Peto OR) for each comparison.
Main Results: Sixty-nine studies with a total of 16,327 women were included. We assessed most of the studies as having an unclear risk of bias, which we interpreted as a high risk of bias. Because of the great number of different comparisons, the average number of included studies in a single comparison was only 1.5 for live birth and 6.1 for clinical pregnancy.Five studies (746 women) compared hCG versus placebo or no treatment. There was no evidence of a difference between hCG and placebo or no treatment except for ongoing pregnancy: Peto OR 1.75 (95% CI 1.09 to 2.81), suggesting a benefit from hCG. There was a significantly higher risk of ovarian hyperstimulation syndrome (OHSS) when hCG was used (Peto OR 3.62, 95% CI 1.85 to 7.06).There were eight studies (875 women) in the second comparison, progesterone versus placebo or no treatment. The results suggested a significant effect in favour of progesterone for the live birth rate (Peto OR 2.95, 95% CI 1.02 to 8.56) based on one study. For clinical pregnancy (CPR) the results also suggested a significant result in favour of progesterone (Peto OR 1.83, 95% CI 1.29 to 2.61) based on seven studies. For the other outcomes the results indicated no difference in effect.The third comparison (15 studies, 2117 women) investigated progesterone versus hCG regimens. The hCG regimens were subgrouped into comparisons of progesterone versus hCG and progesterone versus progesterone + hCG. The results did not indicate a difference of effect between the interventions, except for OHSS. Subgroup analysis of progesterone versus progesterone + hCG showed a significant benefit from progesterone (Peto OR 0.45, 95% CI 0.26 to 0.79).The fourth comparison (nine studies, 1571 women) compared progesterone versus progesterone + oestrogen. Outcomes were subgrouped by route of administration. The results for clinical pregnancy rate in the subgroup progesterone versus progesterone + transdermal oestrogen suggested a significant benefit from progesterone + oestrogen. There was no evidence of a difference in effect for other outcomes.Six studies (1646 women) investigated progesterone versus progesterone + GnRH agonist. We subgrouped the studies for single-dose GnRH agonist and multiple-dose GnRH agonist. For the live birth, clinical pregnancy and ongoing pregnancy rate the results suggested a significant effect in favour of progesterone + GnRH agonist. The Peto OR for the live birth rate was 2.44 (95% CI 1.62 to 3.67), for the clinical pregnancy rate was 1.36 (95% CI 1.11 to 1.66) and for the ongoing pregnancy rate was 1.31 (95% CI 1.03 to 1.67). The results for miscarriage and multiple pregnancy did not indicate a difference of effect.The last comparison (32 studies, 9839 women) investigated different progesterone regimens:intramuscular (IM) versus oral administration, IM versus vaginal or rectal administration, vaginal or rectal versus oral administration, low-dose vaginal versus high-dose vaginal progesterone administration, short protocol versus long protocol and micronized progesterone versus synthetic progesterone. The main results of this comparison did not indicate a difference of effect except in some subgroup analyses. For the outcome clinical pregnancy, subgroup analysis of micronized progesterone versus synthetic progesterone showed a significant benefit from synthetic progesterone (Peto OR 0.79, 95% CI 0.65 to 0.96). For the outcome multiple pregnancy, the subgroup analysis of IM progesterone versus oral progesterone suggested a significant benefit from oral progesterone (Peto OR 4.39, 95% CI 1.28 to 15.01).
Authors' Conclusions: This review showed a significant effect in favour of progesterone for luteal phase support, favouring synthetic progesterone over micronized progesterone. Overall, the addition of other substances such as estrogen or hCG did not seem to improve outcomes. We also found no evidence favouring a specific route or duration of administration of progesterone. We found that hCG, or hCG plus progesterone, was associated with a higher risk of OHSS. The use of hCG should therefore be avoided. There were significant results showing a benefit from addition of GnRH agonist to progesterone for the outcomes of live birth, clinical pregnancy and ongoing pregnancy. For now, progesterone seems to be the best option as luteal phase support, with better pregnancy results when synthetic progesterone is used.
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http://dx.doi.org/10.1002/14651858.CD009154.pub2 | DOI Listing |
Sci Rep
December 2024
Complete Fertility, Princess Anne Hospital, Level F, Coxford Road, Southampton, SO16 5YA, UK.
Elevated progesterone (EP) or inadequate progesterone levels during ART cycle monitoring may lead to cycle cancellations or further progesterone supplementation, but practice varies. It remains controversial whether modifying clinical practice in the presence or absence of EP improves clinical outcomes. This systematic review aims to investigate if progesterone levels at different phases of fresh and frozen ART cycles influence pregnancy outcomes, in particular, that pertaining to day 3 versus day 5 embryo transfers.
View Article and Find Full Text PDFPathol Res Pract
December 2024
Department of Pathology, University of California San Diego, San Diego, CA, USA. Electronic address:
Prolonged cold ischemia time (CIT) and neoadjuvant chemotherapy (NACT) can each independently impact the expression of breast cancer-related biomarkers, but their combined effects are not well studied. Herein, we assessed whether prolonged CIT has a higher modulatory effect on post-NACT biomarker expression in breast cancer specimens than in otherwise similar but non-NACT specimens. Our study cohort included 334 biopsy/resection breast cancer specimen pairs in which immunohistochemistry (IHC for estrogen receptor [ER], progesterone receptor [PR], HER2) and HER2 FISH had been performed on both specimens.
View Article and Find Full Text PDFArkh Patol
December 2024
National Medical Research Center for Obstetrics, Gynecology and Perinatology named after academician V.I. Kulakov, Moscow, Russia.
Objective: To study the features of protein expression of gene in primary breast cancer (BC) and to identify its relationship with regional metastasis.
Material And Methods: The study included 358 cases of primary BC stages I-III without neoadjuvant chemotherapy with an assessment of a number of clinical, morphological and immunohistochemical parameters of the tumor, including NDRG1 protein expression status and its expression level.
Results: In two study groups with and without metastatic lymph node involvement, a statistically significant relationship was found between NDRG1 expression and histological type of BC, tumor grade, estrogen receptors expression, progesterone receptors expression, HER2 status and index Ki-67 (tumor cell proliferative activity).
BMJ Open
December 2024
Health Economics Unit, Department of Applied Health Science, College of Medicine and Health, University of Birmingham, Birmingham, B15 2TT, UK
Objectives: To evaluate the cost-effectiveness of long-acting progestogens (LAP), including levonorgestrel-releasing intrauterine system (LNG-IUS) and depot-medroxyprogesterone acetate (DMPA), compared with the combined oral contraceptives pill (COCP) in preventing recurrence of endometriosis-related pain postsurgery.
Design: Within-trial economic evaluation alongside a multicentre, pragmatic, parallel-group, open-label, randomised controlled trial (Preventing Recurrence of Endometriosis by means of Long-Acting Progestogen Therapy trial).
Setting: Thirty-four UK hospitals recruiting participants from November 2015 to March 2019.
Reprod Biol Endocrinol
December 2024
Department of Reproductive Medicine, University of Lille, CHU Lille, Lille, 59000, France.
Research Question: To determine whether the use of oral dydrogesterone (DYD) in luteal phase support (LPS) during an artificial cycle provides equivalent clinical and ongoing pregnancy, delivery and miscarriage rates as micronized vaginal progesterone (MVP) in oocyte donation recipients.
Design: This was a retrospective observational study of prospectively collected data from the assisted reproductive technology (ART) Department of Lille University Hospital from July 2018 to July 2022. All recipients underwent endometrial preparation by an artificial cycle.
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