Project description:The optimal protocol for endometrial preparation in patients with infertility remains unclear. Due to this, the current study retrospectively analyzed 1,589 patients with infertility and regular menstrual cycles to assess reproductive outcomes per embryo transferred and per embryo transfer (ET) cycle following the transfer of frozen-thawed embryos (FET) in a modified natural cycle (mNC) or hormone therapy cycle (HT) with or without gonadotropin-releasing hormone agonist (GnRHa)-induced pituitary suppression. The molecular mechanisms involved were also studied using tissues from endometrial biopsies. Patients who underwent FET were assigned to 5 groups as follows: Group A underwent a mNC (n=276); group B (n=338) received estradiol (E2) and progesterone (P4); group C received 1 cycle of GnRHa, E2 and P4 (n=323); group D received 2 cycles of GnRHa, E2 and P4 (n=329); and group E received 3 cycles of GnRHa, E2 and P4 (n=323). Tissues from endometrial biopsies of 91 patients performed on the day of ET were tested for endometrial receptivity marker mRNA expression and microRNA (miR)-223-3p mRNA. Furthermore, endometrial stromal cells (ESCs) were used for an in-depth study of the molecular mechanisms involved. Among the 5 groups of patients, implantation rates, clinical pregnancy rates and live birth rates were not significantly different. However, endometrial receptivity was enhanced in group E when compared with groups A-D, which was associated with endometrial leukemia inhibitory factor (LIF), osteopontin, vascular endothelial growth factor, integrin ?3 and homeobox gene 10 and 11 mRNA upregulation, and miR-223-3p miRNA downregulation. Transfection of ESCs with an miR-223-3p mimic significantly reduced levels of LIF mRNA and protein. In addition, pre-treating ESCs with GnRHa upregulated mRNA and protein expression of the decidualization markers prolactin and insulin-like growth factor binding protein-1 in a time-dependent manner. In conclusion, these results indicated that HT with GnRHa may be a potential endometrial preparation protocol for FET.
Project description:Research question:Endometrial preparation is one of the most important steps for ensuring frozen embryo transfer success. However, there is no clear evidence that identifies an optimal endometrial preparation protocol for frozen embryo transfer. In addition, in studies that assessed which were the optimal endometrial preparation protocols, few analyzed the stage and the number of embryos. This study compared the pregnancy outcomes and perinatal obstetric complications of patients who were transferred two cleavage-stage (day 2 or day 3) frozen embryos with the natural cycle and those with the hormone replacement therapy cycle. Design:This study was a secondary analysis of data from a multicentre randomized controlled trial designed to compare the pregnancy and perinatal outcomes after frozen versus fresh embryo transfer. In this study, a total of 908 patients who were transferred two cleavage-stage (day 2 or day 3) embryos in the original trial were analyzed. Pregnancy outcomes and perinatal obstetric complications after the natural cycle and the hormone replacement therapy cycle were compared. Result:We found the endometrium in the natural group was significantly thicker than the hormone replacement therapy cycle group (p<0.01). The implantation rate (42.6% vs 37.3% p=0.049) showed a significant difference between the natural cycle group and the hormone replacement therapy cycle group. Compared to the natural cycle group, the hormone replacement therapy cycle group was associated with an increased risk of caesarean section (72.3% vs 84.5, p=0.009). Conclusion:The natural cycle protocol yielded thicker endometria, a higher implantation rate and a lower risk of caesarean section than the hormone replacement therapy protocol in the transfer of two cleavage-stage frozen embryos. The natural cycle protocol was the better endometrial preparation protocol for frozen embryo transfer.
Project description:BackgroundWomen undergoing infertility treatment have poor quality of life. This may cause them to withdraw from or refuse treatment. Women undergoing frozen embryo transfer have a treatment interval. The aim of this study was to investigate the status quo of the fertility quality of life in women undergoing frozen embryo transfer and analyse its predictors.MethodsA cross-sectional survey was conducted from August 2019 to August 2020 among women undergoing frozen embryo transfer in a tertiary hospital reproductive centre in Beijing, China. The survey collected demographic characteristics and treatment data and included the fertility problem inventory, the fertility quality of life scale (FertiQoL) and the state-trait anxiety scale. Multiple linear stepwise regression was used to explore the predictors of fertility quality of life.ResultsIn total, 1062 women completed the survey. Participants reported that they had high levels of fertility-related stress and anxiety during treatment. They also had lower fertility-related quality of life, and the Treatment FertiQoL scored the lowest. The regression results showed that social concern, trait anxiety, duration of treatment and age were risk factors for diminished fertility quality of life.ConclusionChinese women undergoing frozen embryo transfer have relatively poor quality of life. The potential predictors of fertility quality of life include social concern, trait anxiety, duration of treatment and age.
Project description:Studies have consistently reported a significantly reduced incidence of ectopic pregnancy (EP) for frozen-thawed embryo transfer (ET) cycles compared with fresh cycles. However, only a few studies reported an association between endometrial preparation protocols on EP and results were conflicting. A registry-based retrospective cohort study of 153,354 clinical pregnancies following frozen single ETs between 2014 and 2017 were conducted, of which 792 cases of EP (0.52%) were reported. Blastocyst embryo transfers accounted for 87% of the total sample and were significantly associated with a decreased risk for EP compared with early cleavage ET (0.90% vs. 0.46%, adjusted OR = 0.50, 95% CI, 0.41 to 0.60). Compared with natural cycles, hormone replacement cycles (HRC) demonstrated a similar risk for EP (0.53% vs. 0.47%, adjusted OR = 1.12, 95% CI, 0.89 to 1.42). Subgroup analysis with or without tubal factor infertility and early cleavage/blastocyst ETs demonstrated similar non-significant associations. Endometrial preparation protocols using clomiphene (CC) were associated with a significantly increased risk for EP (1.12%, adjusted OR = 2.34; 95% CI, 1.38 to 3.98). These findings suggest that HRC and natural cycles had a similar risk for EP. Endometrial preparation using CC was associated with an increased risk of EP in frozen embryo transfer cycles.
Project description:The objective was to compare the endometrial thickness (ET) in a frozen embryo transfer (FET) cycle between transdermal and vaginal estrogen. Our secondary objectives were to compare the patient satisfaction and the pregnancy outcomes. Prospective monocentric cohort study between 01/2017 and 12/2017 at a single institution. Choice of administration was left to the patient. 119 cycles had transdermal estrogen (T-group) and 199 had vaginal estrogen (V-group). The ET at 10 ± 1 days of treatment was significantly higher in the T-group compared to the V-group (9.9 vs 9.3 mm, p = 0.03). In the T-group, the mean duration of treatment was shorter (13.6 vs 15.5 days, p < 0.001). The rate of cycle cancelation was comparable between the two groups (12.6% vs 8.5%, p = 0.24). Serum estradiol levels were significantly lower (268 vs 1332 pg/ml, p < 0.001), and serum LH levels were significantly higher (12.1 ± 16.5 vs 5 ± 7.5 mIU/ml, p < 0.001) in the T-group. Patient satisfaction was higher in the T-group (p = 0.04) and 85.7% (36/42) of women who had received both treatments preferred the transdermal over the vaginal route. Live birth rates were comparable between the two groups (18% vs 19%, p = 0.1). Transdermal estrogen in artificial FET cycles was associated with higher ET, shorter treatment duration and better tolerance.
Project description:BackgroundPrevious studies have focused on pregnancy outcomes after frozen embryo transfer (FET) performed using different endometrial preparation protocols. Few studies have evaluated the effect of endometrial preparation on pregnancy-related complications. This study was designed to explore the association between different endometrial preparation protocols and adverse obstetric and perinatal complications after FET.MethodsWe retrospectively included all FET cycles (n = 12,950) in our hospital between 2010 and 2017, and categorized them into three groups, natural cycles (NC), hormone replacement therapy (HRT) and ovarian stimulation (OS) protocols. Pregnancy-related complications and subsequent neonatal outcomes were compared among groups.ResultsAmong all 12,950 FET cycles, the live birth rate was slightly lower for HRT cycles than for NC (HRT vs. NC: 28.15% vs. 31.16%, p < 0.001). The pregnancy loss rate was significantly higher in OS or HRT cycles than in NC (HRT vs. NC: 17.14% vs. 10.89%, p < 0.001; OS vs. NC: 16.44% vs. 10.89%, p = 0.001). Among 3864 women with live birth, preparing the endometrium using OS or HRT protocols increased the risk of preeclampsia, and intrahepatic cholestasis of pregnancy (ICP) in both singleton and multiple deliveries. Additionally, OS and HRT protocols increased the risk of low birth weight (LBW) and small for gestational age (SGA) in both singletons and multiples after FET.ConclusionCompared with HRT or OS protocols, preparing the endometrium with NC was associated with the decreased risk of pregnancy-related complications, as well as the decreased risk of LBW and SGA after FET.
Project description:ImportanceIn in vitro fertilization cycles using autologous oocytes, data have demonstrated higher live birth rates following cryopreserved-thawed embryo transfers compared with fresh embryo transfers. It remains unknown if this association exists in cycles using freshly retrieved donor oocytes.ObjectiveTo test the hypothesis that in freshly retrieved donor oocyte cycles, a fresh embryo transfer is more likely to result in a live birth compared with a cryopreserved-thawed embryo transfer.Design, setting, and participantsRetrospective cohort study using national data collected from the Society for Assisted Reproductive Technology for 33 863 recipients undergoing fresh donor oocyte cycles in the US between January 1, 2014 and December 31, 2017.ExposuresFresh embryo transfer and cryopreserved-thawed embryo transfer.Main outcomes and measuresThe primary outcome was live birth rate; secondary outcomes were clinical pregnancy rate and miscarriage rate. Analyses were adjusted for donor age, day of embryo transfer, use of a gestational carrier, and assisted hatching.ResultsRecipients of fresh and cryopreserved-thawed embryos had comparable median age (42.0 [interquartile range {IQR}, 37.0-44.0] years vs 42.0 [IQR, 36.0-45.0] years), gravidity (1 [IQR, 0-2] vs 1 [IQR, 0-3]), parity (0 [IQR, 0-1] vs 1 [IQR, 0-1]), and body mass index (24.5 [IQR, 21.9-28.7] vs 24.4 [IQR, 21.6-28.7]). Of a total of 33 863 recipients who underwent 51 942 fresh donor oocyte cycles, there were 15 308 (29.5%) fresh embryo transfer cycles and 36 634 (70.5%) cryopreserved-thawed embryo transfer cycles. Blastocysts were transferred in 92.4% of fresh embryo transfer cycles and 96.5% of cryopreserved-thawed embryo transfer cycles, with no significant difference in the mean number of embryos transferred. Live birth rate following fresh embryo transfer vs cryopreserved-thawed embryo transfer was 56.6% vs 44.0% (absolute difference, 12.6% [95% CI, 11.7%-13.5%]; adjusted relative risk [aRR], 1.42 [95% CI, 1.39-1.46]). Clinical pregnancy rates were 66.7% vs 54.2%, respectively (absolute difference, 12.5% [95% CI, 11.6%-13.4%]; aRR, 1.34; [95% CI, 1.31-1.37]). Miscarriage rates were 9.3% vs 9.4%, respectively (absolute difference, 0.2% [95% CI, -0.4% to 0.7%]); aRR, 0.98 [95% CI, 0.91-1.07]).Conclusions and relevanceIn this retrospective cohort study of women undergoing assisted reproduction using freshly retrieved donor oocytes, the use of fresh embryo transfers compared with cryopreserved-thawed embryo transfers was associated with a higher live birth rate. However, interpretation of the findings is limited by the potential for selection and confounding bias.
Project description:PurposeTo evaluate whether endometrial compaction using sequential transvaginal ultrasound is associated with improved live birth rates in medicated single euploid frozen embryo transfer (FET) cycles.MethodsProspective observational cohort study at a private fertility clinic. Patients who underwent FETs between January and December 2018 were assessed for inclusion. The change in endometrial thickness between the end of the estrogen phase and the day before embryo transfer, measured by sequential transvaginal ultrasound, was used to categorize cycles with compaction (≥ 5%), no change, or expansion (≥ 5%). FET cycle outcomes were then compared between groups. The primary outcome was live birth. Secondary outcomes include clinical pregnancy rate and rate of spontaneous abortion.ResultsOf the 259 single euploid medicated FETs performed during the study period, only 43/259 (16.6%) of the cycles demonstrated ≥ 5% compaction, whereas 152/259 (58.7%) expanded and 64/259 (24.7%) were unchanged. Live birth rates did not differ between cycles with compaction (58.1%), no change (54.7%), or expansion (58.6%), p = 0.96. Clinical pregnancy and spontaneous abortion rates were also similar between groups.ConclusionThe vast majority of cycles did not demonstrate endometrial compaction. Endometrial compaction is not associated with live birth rate or spontaneous abortion rate in medicated single euploid FETs in this cohort.
Project description:Polycystic ovary syndrome (PCOS) patients are at increased risk of pregnancy complications, which may impair pregnancy outcome. Transfer of fresh embryos after superovulation may lead to abnormal implantation and placentation and further increase risk for pregnancy loss and complications. Some preliminary data suggest that elective embryo cryopreservation followed by frozen-thawed embryo transfer into a hormonally primed endometrium could result in a higher clinical pregnancy rate than that achieved by fresh embryo transfer.This study is a multicenter, prospective, randomized controlled clinical trial (1:1 treatment ratio of fresh vs. elective frozen embryo transfers).. A total of 1,180 infertile PCOS patients undergoing the first cycle of in vitro fertilization (IVF) or intracytoplasmic sperm injection will be enrolled and randomized into two parallel groups. Participants in group A will undergo fresh embryo transfer on day 3 after oocyte retrieval, and participants in group B will undergo elective embryo cryopreservation after oocyte retrieval and frozen-thawed embryo transfer in programmed cycles. The primary outcome is the live birth rate. Our study is powered at 80 to detect an absolute difference of 10 at the significance level of 0.01 based on a two-sided test.We hypothesize that elective embryo cryopreservation and frozen-thawed embryo transfer will reduce the incidence of pregnancy complications and increase the live birth rate in PCOS patients who need IVF to achieve pregnancy.ClinicalTrials.gov Identifier: NCT01841528.
Project description:Transcriptome profile of receptive phase endometrium among infertile women with recurrent implantation failure (RIF) in two different endometrial preparation protocols for FET was analyzed: natural cycle (NC-FET) vs. artificial cycle (AC-FET). Fifteen endometrial biopsy samples were obtained: women with unexplained RIF (n = 5) in natural cycles for FET (NC-FET), women with unexplained RIF undergoing artificial endometrial preparation (n = 5) for FET (AC-FET), and healthy women (n = 5) with proven fertility in natural cycles (NC-FC) (Control group). All endometrial biopsies were obtained during the mid-secretory phase, at the time of ‘window of implantation’.