OBJECTIVE: To evaluate whether the type of frozen embryo transfer (FET) regimen - ovulation-induced regimens vs. hormone replacement therapy regimens (HRT) - is associated with live birth rates and the risk of hypertensive diseases of pregnancy (HDP) in women with polycystic ovary syndrome (PCOS).
METHODS: All studies in PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were searched using a combination of MeSH terms and keywords. Inclusion criteria included studies on women with a diagnosis of PCOS, utilization of FET, and reporting of pregnancy and/or obstetric outcomes. Studies were excluded if they were case series or conference abstracts or used other FET regimens. A random effects meta-analysis was performed. Primary outcomes include relative risk (RR) of live birth and HDP.
RESULTS: Eleven studies were included in the meta-analysis for the final review. Ovulation-induced regimens were associated with a higher live birth rate (8 studies, RR 1.14 [95% CI 1.08, 1.21]) compared to HRT regimens. The risk of HDP (3 studies RR 0.78 [95% CI 0.53, 1.15]) was not significantly different. Ovulation-induced regimens were associated with a lower miscarriage rate (9 studies, RR 0.67 [95% CI 0.59-0.76]). Rates of clinical pregnancy (10 studies, RR 1.05 [95% CI 0.99, 1.11]) and ectopic pregnancy (7 studies, RR 1.40 [95% CI 0.84, 2.33]), were not significantly different.
CONCLUSIONS: This SR/MA demonstrates that for women with PCOS, ovulation-induced FET regimens are associated with higher rates of live birth and lower rates of miscarriage compared to HRT regimens.

OBJECTIVE: This study was aimed to systematically evaluate the efficacy of artificial cycle-prepared frozen-thawed embryo transfer (FET) with or without gonadotrophin-releasing hormone agonist (GnRH-a) pretreatment for women with polycystic ovary syndrome (PCOS).
METHODS: The analysis was carried out by searching the PubMed, EMBASE, and CNKI databases with a combination of keywords before October 2021. The available studies of the effects of GnRH-a pretreatment or no pretreatment on FET in PCOS patients were considered. The risk ratios (RRs) or standardized mean differences (SMD) with 95% confidence intervals (CIs) were calculated with using subgroups and sensitivity analysis. The quality evaluation for this analysis was followed.
RESULTS: Seventeen studies including 3646 women were analyzed. GnRH-a pretreatment was significantly associated with a higher implantation rate (RR = 1.12, 95%CI: 1.00-1.24) and clinical pregnancy rate (RR = 1.19, 95%CI: 1.08-1.32) than the placebo. Moreover, in the GnRH-a pretreatment group, significant differences were detected for increasing the endometrium thickness among PCOS patients (SMD = 0.56, 95%CI: 0.20-0.92). However, for RCTs subgroup, no differences were observed, even after sensitivity analyses. In addition, the miscarriage rates, ectopic pregnancy rates, multiple pregnancy rates, and live birth rates were similar in both two groups.
CONCLUSIONS: Endometrial preparation using GnRH agonist pretreatment prior to FET seems to be the better choice for PCOS patients. However, well-designed RCTs are required for confirmation.

Frozen-thawed embryo transfer (FET) has been a viable alternative to fresh embryo transfer in recent years because of the improvement in vitrification methods. Laboratory-based studies indicate that complex molecular and morphological changes in endometrium during the window of implantation after exogenous hormones with controlled ovarian stimulation may alter the interaction between the embryo and endometrium, leading to a decreased implantation potential. Based on the results obtained from randomized controlled studies, increased pregnancy rates and better perinatal outcomes have been reported following FET. Compared to fresh embryo transfer, fewer preterm deliveries, and reduced incidence of ovarian hyperstimulation syndrome were found after FETs, yet there is a trend of increased pregnancy-related hypertensive diseases in women receiving FET. Despite the increased application of FET, the search for the most optimal priming protocol for the endometrium is still undergoing. Three available FET protocols have been proposed to prepare the endometrium: i) natural cycle (true natural cycle and modified natural cycle) ii) artificial cycle (AC) or hormone replacement treatment cycle iii) mild ovarian stimulation (mild-OS) cycle. Emerging evidence suggests that the optimal timing for FET using warmed blastocyst transfer is the LH surge+6 day, hCG administration+7 day, and the progesterone administration+6 day in the true natural cycle, modified natural cycle, and AC protocol, respectively. Although still controversial, better clinical pregnancy rates and live birth rates have been reported using the natural cycle (true natural cycle/modified natural cycle) compared with the AC protocol. Additionally, a higher early pregnancy loss rate and an increased incidence of gestational hypertension have been found in FETs using the AC protocol because of the lack of a corpus luteum. Although the common clinical practice is to employ luteal phase support (LPS) in natural cycles and mild-OS cycles for FET, the requirement for LPS in these protocols remains equivocal. Recent findings obtained from RCTs do not support the routine application of endometrial receptivity testing to optimize the timing of FET. More RCTs with rigorous methodology are needed to compare different protocols to prime the endometrium for FET, focusing not only on live birth rate, but also on maternal, obstetrical, and neonatal outcomes.

Successful outcomes of in vitro fertilization (IVF) rely on both the formation of a chromosomally normal embryo and its implantation in a receptive endometrium. Pre-implantation genetic testing for aneuploidy (PGT-A) has been widely accepted as a tool to assess the viability of an embryo. In 2011, the endometrial receptivity array (ERA) was first published as a tool to determine when the endometrium is most receptive to an embryo, commonly referred to as the \"window of implantation\" (WOI). The ERA uses molecular arrays to assess proliferation and differentiation in the endometrium and screens for inflammatory markers. Unlike PGT-A, there has been dissent within the field concerning the efficacy of the ERA. Many studies that contest the success of the ERA found that it did not improve pregnancy outcomes in patients with an already-good prognosis. Alternatively, studies that utilized the ERA in patients with repeated implantation failure (RIF) and transfer of known euploid embryos demonstrated improved outcomes. This review aims to describe the ERA as a novel technique, review the various settings that the ERA may be used in, such as natural frozen embryo transfer (nFET) and hormone replacement therapy frozen embryo transfer (HRT-FET), and provide a summary of the recent clinical data for embryo transfers in patients with RIF utilizing the ERA.

To investigate the impact of recryopreservation on embryo viability and the outcomes of in vitro fertilization (IVF) by comparison with single cryopreservation. There is a lack of consensus and reliable evidence regarding the impact of recryopreservation techniques on human embryos, particularly with respect to embryo viability and IVF outcomes.
Systematic review and meta-analysis.
Not applicable.
Various databases such as PubMed, Embase, Cochrane Library, and Scopus were searched until October 10, 2022. All comparative studies comparing embryonic and IVF outcomes between repeated and single cryopreservation of embryos were included. The random-effect and fixed-effect meta-analysis models were used to pool the odds ratio (OR) and corresponding 95% confidence intervals (CIs). A subgroup analysis was performed based on different methods of cryopreservation and different times of embryo cryopreservation or transfer.
Outcomes referring to embryo surviva l, IVF outcomes (including clinical pregnancy rate, embryo implantation rate, miscarriage rate, and live birth rate), and neonatal outcomes (including low birth weight rate and preterm birth rate) were evaluated.
Fourteen studies were eligible for the present meta-analysis, involving 4,525 embryo transfer cycles in total (3,270 cycles with single cryopreservation [control group] and 1,255 with recryopreservation [experimental group]). Decreased embryo survival (OR, 0.51; 95% CI, 0.27-0.96) and clinical pregnancy rates (OR, 0.47; 95% CI, 0.23-0.96) were found in embryos that were recryopreserved by slow freezing. The live birth rate of revitrified embryos was also notably affected (OR, 0.60; 95% CI, 0.38-0.94). Overall, recryopreservation resulted in a decreased live birth rate (OR, 0.67; 95% CI, 0.50-0.90) and an increased miscarriage rate (OR, 1.52; 95% CI, 1.16-1.98) compared with single cryopreservation. No significant difference was found in neonatal outcomes. When embryos were cryopreserved and transferred at the blastocyst stage, both the embryo implantation rate (OR, 0.59; 95% CI, 0.39-0.89) and live birth rate (OR, 0.60; 95% CI, 0.37-0.96) were significantly different between the 2 groups.
The present meta-analysis suggested that recryopreservation, compared with single cryopreservation, can lead to impaired embryo viability and a lower rate of IVF success, with no affected neonatal outcomes. Clinicians and embryologists should retain a cautious attitude toward recryopreservation strategies.
CRD42022359456.

The necessity of progesterone supplementation for luteal phase support (LPS) in natural cycle frozen embryo transfer (NC-FET) cycles warrants further confirmation.
To investigate the effect of progesterone supplementation for LPS on the reproductive outcomes of patients undergoing NC-FET cycles.
The PubMed, Ovid-Embase, Cochrane Library, Web of Science, CNKI, Wanfang, VIP, and CBM were electronically searched. The search time frame was from inception up to September 2022.
Randomized controlled trials (RCTs) that used progesterone for LPS in NC-FET cycles, including true NC-FET cycles (tNC-FET) and modified NC-FET cycles (mNC-FET), were included. The counted data were analyzed using relative risk (RR) as the effect-size statistic, and each effect size was assigned its 95% confidence interval (CI).
The primary outcomes were the live birth rate (LBR) and the clinical pregnancy rate (CPR), and the secondary outcome was the miscarriage rate.
Four RCTs were included, which involved 1116 participants. The results of the meta-analysis showed that progesterone supplementation was associated with increased LBR (RR, 1.42; 95% CI, 1.15-1.75; I2 = 0%, moderate-quality evidence) and CPR (RR, 1.30, 95% CI, 1.07-1.57; I2 = 0%, moderate-quality evidence) in patients undergoing NC-FET cycles. Subgroup analysis showed that progesterone supplementation was associated with higher LBR and CPR in tNC-FET cycles. However, no association was found between increased LBR and CPR in mNC-FET cycles. In addition, only one RCT reported that oral dydrogesterone had similar CPR and miscarriage rate compared with vaginal progesterone in mNC-FET cycles.
Overall, moderate-quality evidence suggested that progesterone supplementation for LPS was associated with increased LBR and CPR in NC-FET cycles. Progesterone supplementation was associated with a higher LBR and CPR in tNC-FET cycles. However, the effectiveness of progesterone supplementation in mNC-FET cycles should be further verified by larger RCTs. Low to very low-quality evidence indicated that oral dydrogesterone and vaginal progesterone have similar reproductive outcomes in mNC-FET cycles, which requires further study, especially in tNC-FET cycles.
PROSPERO CRD42022355550 (https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=355550) was registered on September 3, 2022.

To investigate the impact of endometrial receptivity array (ERA) before frozen embryo transfer in patients undergoing in vitro fertilization (IVF). There is a lack of consensus regarding the use of ERA for increasing the success rate of IVF cycles, mainly in terms of the live birth rate.
PubMed, Web of Science and Embase were searched from inception up to February 15, 2022.
Not applicable.
Patients undergoing ERA vs no ERA before frozen embryo transfer.
Only comparative studies evaluating pregnancy rates of patients undergoing frozen embryo transfer cycles with or without prior ERA were included. Inter-study heterogeneity was also assessed using Cochrane\'s Q test and the I2 statistic. The random-effects model was used to pool the odds ratio (OR) with the corresponding 95% confidence intervals (CIs). Subgroup analyses were performed to investigate the impact of ERA on pregnancy rates according to the number of previous embryo transfer (ET) failures (≤ 2 previous failed ETs vs. > 2 failed ETs, defined as recurrent implantation failure). Separate analyses were performed according to the study design and adjustment for confounders.
The primary outcomes of the study were live birth rate and/or ongoing pregnancy rate. Implantation rate, biochemical pregnancy rate, clinical pregnancy rate, and miscarriage rate were considered secondary outcomes.
Eight studies (representing data on n = 2,784 patients; n = 831 had undergone ERA and n = 1,953 without ERA) were found to be eligible for this meta-analysis. The live birth or ongoing pregnancy rate for the ERA group was not significantly different compared with the non-ERA group (OR, 1.38; 95% CI, 0.79-2.41; I2 83.0%), nor was a difference seen in subgroup analyses based on the number of previous failed ETs. The rates of implantation, biochemical pregnancy, clinical pregnancy, and miscarriage were also comparable between the ERA and the non-ERA groups. After separate analyses according to the study design and adjustment for confounding factors, overall pooled estimates remained statistically nonsignificant.
The findings of the current meta-analysis did not reveal a significant change in the rate of pregnancy after IVF cycles using ERA, and it is not clear whether ERA can increase the pregnancy rate or not.
Prospectively registered in PROSPERO (CRD42022310862).

In recent years, the growing use of ART (assisted reproductive techniques) has led to a progressive improvement of protocols; embryo freezing is certainly one of the most important innovations. This technique is selectively offered as a tailored approach to reduce the incidence of multiple pregnancies and, most importantly, to lower the risk of developing ovarian hyperstimulation syndrome when used in conjunction with an ovulation-triggering GnRH antagonist. The increase in transfer cycles with frozen embryos made it possible to study the effects of the technique in children thus conceived. Particularly noteworthy is the increase in macrosomal and LGA (large for gestational age) newborns, in addition to a decrease in SGA (small for gestational age) and LBW (low birth weight) newborns. The authors aimed to outline a broad-ranging narrative review by summarizing and elaborating on the most important evidence regarding the neonatal outcome of children born from frozen embryos and provide information on the medium and long-term follow- up of these children. However, given the relatively recent large-scale implementation of such techniques, further studies are needed to provide more conclusive evidence on outcomes and implications.

OBJECTIVE: To assess the effects of dienogest on segmented in vitro fertilization (IVF) and frozen-thawed embryo transfer (FET) for a patient with adenomyosis.
METHODS: A 33-year-old female with primary infertility for 3 years had dysmenorrhea and hypermenorrhea. Diagnosis of adenomyosis was made with a sonographic exam and an elevated cancer antigen 125 (CA-125, 310 U/mL). Her early follicular hormone profile (anti-müllerian hormone, AMH, 8 ng/mL) was normal. After repeated controlled ovarian stimulation (COS) and failed intrauterine insemination (IUI), she underwent IVF. Controlled ovarian stimulation using gonadotropin-releasing hormone (GnRH) antagonist protocol was performed with the blastocyst freeze-all IVF cycle. Pretreatment with two months of GnRH agonist (GnRHa) and frozen-thawed embryo transfer did not result in pregnancy. Subsequently, three months of long-term pretreatment with dienogest was given, and the CA-125 level was markedly reduced. Frozen-thawed blastocyst stage embryo transfer was provided, and a singleton pregnancy was achieved.
CONCLUSIONS: Dienogest, a novel progestin highly selective for progesterone receptors, may benefit the pregnancy outcomes of infertile patients with adenomyosis adopting segmented IVF with FET.

To investigate the optimal route of progesterone administration for luteal phase support in a frozen embryo transfer.
Systematic review.
Women undergoing frozen embryo transfer (FET).
We conducted an extensive database search of Medline (PubMed), Embase, Web of Science, and Cochrane Trials Register using relevant keywords and their combinations to find randomized controlled trials (RCTs) comparing the routes (i.e., oral, vaginal, intramuscular) of progesterone administration for luteal phase support (LPS) in artificial FET.
Clinical pregnancy, live birth, miscarriage.
Four RCTs with 3245 participants undergoing artificial endometrial preparation (EP) cycles during FET were found to be eligible. Four trials compared vaginal progesterone with intramuscular progesterone and two trials compared vaginal progesterone with oral progesterone. One study favored of vaginal versus oral progesterone for clinical pregnancy rates (RR 0.45, 95% CI 0.22-0.92) and other study favored intramuscular versus vaginal progesterone for clinical pregnancy rates (RR 1.46, 95% CI 1.21-1.76) and live birth rates (RR 1.62, 95% CI 1.28-2.05). Tabulation of overall evidence strength assessment showed low-quality evidence on the basis that for each outcome-comparison pair, there were deficiencies in either directness of outcome measurement or study quality.
There was little consensus and evidence was heterogeneous on the optimal route of administration of progesterone for LPS during FET in artificial EP cycles. This warrants more trials, indirect comparisons, and network meta-analyses.
CRD42021251017.