Higher Live Birth Rate Research Articles

Should women receive luteal support following natural cycle frozen embryo transfer? A systematic review and meta-analysis

Spontaneous ovulation during a natural menstrual cycle is frequently used for timing frozen embryo transfer (FET). Nevertheless, it remains unclear whether or not women should receive luteal phase support (LPS) following natural cycle frozen embryo transfer (NC-FET). The aim of this systematic review and meta-analysis was to study whether the administration of LPS improves the reproductive outcome following NC-FET. We conducted a systematic search of the literature published in Medline/PubMed, Embase and the Cochrane Library, from January 2000 until December 2020. We included all original English, peer-reviewed articles, irrespective of the study design. The search strategy included keywords related to NC-FET and luteal phase support. Studies reporting the results of artificial or stimulated FET cycles were excluded. Our systematic search generated 416 records. After screening, eight studies were included in the review and seven studies were included in the meta-analysis. Two studies (n = 858) used hCG and six studies (n = 1507) used progesterone for luteal support. Four studies were randomised controlled trials (RCTs), whereas the other four were historic cohort studies. In a meta-analysis using a random effects model, hCG administration for LPS did not increase the clinical pregnancy rate (CPR) (two studies, odds ratio (OR) 0.85, 95% CI 0.64-1.14). On the other hand, progesterone LPS was associated with a higher CPR (five studies, OR 1.48, 95% CI 1.14-1.94), and a higher live birth rate (LBR) (three studies, OR 1.67, 95% CI 1.19-2.36). The association between progesterone LPS and the LBR remained significant after excluding non-randomised studies. The available evidence indicates that progesterone administration for LPS is beneficial following NC-FET. There is no evidence to support the administration of hCG for LPS in these cases. Additional large RCTs are necessary to improve the quality of evidence and validate our findings.

Effects of the Interval between Ovulation Induction using Clomiphene Citrate and Frozen Embryo Transfer on Pregnancy Outcome

Abstract Objective: To explore the best timing for frozen embryo transfer (FET) after ovarian stimulation and egg retrieval using the clomiphene citrate (CC) + human menopausal gonadotropin (hMG) ovulation induction regimen through a retrospective analysis. Methods: Data of patients who underwent CC + hMG ovulation induction and FET from January 2014 to December 2019 were analyzed retrospectively. The patients were divided into three groups according to the interval from egg retrieval to FET: CC1 (within 1 menstrual cycle), CC2 (2 menstrual cycles), and CC3 (≥ 3 menstrual cycles). Indicators such as hormone levels and pregnancy outcomes were recorded to explore the effect of different intervals on pregnancy outcome. Results: A total of 1,082 transfer cycles were included in this retrospective analysis. The implantation, clinical pregnancy, and live birth rates in the CC1 group were significantly lower than those in the CC2 and CC3 groups (P < 0.05). The E2/P4 ratio on progesterone injection day (3 days before thawed embryo transfer) was lower in the CC1 group than in the other groups (P < 0.05). After adjusting for all factors using multifactor regression analysis, the interval between egg retrieval and FET was found to be an independent predictor of the implantation, pregnancy, and live birth rates. Conclusion: An interval of more than one menstrual cycle between the day of egg retrieval after ovarian stimulation with the CC + hMG ovulation induction regimen and the day of FET can result in high implantation, clinical pregnancy, and live birth rates, which can lead to an improved pregnancy outcome.

Comparison of the efficacy of different progesterone regimens in blastocyst frozen-thawed embryo transfer cycles

Aim: The progesterone’s optimal route for luteal phase support (LPS) in frozen-thawed embryo transfer (FET) cycles is controversial. This study investigates the effect of three treatment regimens of progesterone: vaginal, oral, and subcutaneous form for LPS in FET cycles.
 Material and Method: Blastocyst cryopreserved FET cycles utilizing vaginal, subcutaneous, or oral forms of progesterone between December 2018 and May 2020 were included. The main outcome was to compare clinical pregnancy rates (CPR), ongoing pregnancy rates (OPR), and live birth rates (LBR) in different progesterone groups. 
 Results: A total of 434 cycles were included, of which 200 utilized vaginal, 124 utilized subcutaneous, and 110 utilized oral forms. Demographic and cycle characteristics were similar between all three groups. Compared to cycles utilizing vaginal, subcutaneous, and oral forms, CPR, OPR, and LBR differ significantly between the three groups (p-value = 0.000). Miscarriage was calculated according to the number of days after embryo transfer, and it was shown that the subcutaneous group had the lowest rate of miscarriage with 11 cases (8.8%). The highest OPR was associated with the subcutaneous group with 67 (54%), followed by the vaginal group with 92 (46%). The highest LBR was in the subcutaneous group, with 59 (47.6%) cases. The oral group was significantly less successful 29 ( 26.4%) than the subcutaneous and vaginal groups. 
 Conclusion: Our study results showed that subcutaneous and vaginal progesterone performed better than oral progesterone for LPS in patients undergoing FET. All three forms of progesterone administration were safe and well-tolerated.

The Endometrial Immune Profiling May Positively Affect the Management of Recurrent Pregnancy Loss.

IntroductionThe endometrial immune profiling is an innovative approach based on the analysis of the local immune reaction occurring in the endometrium at the time of the embryo implantation. By documenting the local immune activation during the period of uterine receptivity, we aim to detect and correct potential imbalances before and at the very beginning of placentation. The main objective of the study was to analyze in women with a history of repeated pregnancy loss (RPL) the association of personalized strategies based on immune dysregulations with live birth rates. The secondary objective was to highlight the main prognostic factors for live births.MethodsThis is an observational retrospective analysis of 104 patients with RPL, included between January 2012 and December 2019. Inclusion criteria included a spontaneous fertility with at least three miscarriages, an assessment including a three-dimension ultrasound scan, an endometrial biopsy for uterine immune profiling and a follow-up over at least 6 months with personalized care if indicated after the complete assessment. We defined as a success if the patients had a live birth after the suggested plan, as a failure if the patient either did not get pregnant or experienced a new miscarriage after the targeted therapies.ResultsUterine immune profiling was the only exploration to be significantly associated with a higher live birth rate (LBR) if a dysregulation was identified and treated accordingly (55% vs 45%, p=0.01). On the contrary, an absence of local dysregulation (resulting in an apparently balanced immune environment) was associated with a higher risk of a new miscarriage, suggesting that the cause inducing RPL still needed to be identified. Independently of age and AMH level, dysregulated immune profile is significatively associated with 3 times higher LBR than a non-deregulated profile (OR=3.4 CI 95%1.27-9.84) or five times in case of an overactive profile treated by immunotherapy (OR=5 CI 95% 1.65-16.5). The usage of ART was significantly associated with lower LBR regardless of the presence of a subfertility factor (p=0.012). Personalization of medical care using natural cycle or simple hormonal stimulation is associated with a significantly higher LBR than personalization including ART treatments regardless of maternal age and AMH level (OR= 2.9 CI 95% 1.03-8.88).ConclusionOur study suggests that some endometrial immune profiles with targeted management of RPL are associated with a higher rate of LBR. ART may be negatively associated with LBR.

GnRH antagonist versus depot GnRH agonist protocol in polycystic ovary syndrome (PCOS): analysis using propensity score matching

IntroductionWomen with PCOS have been reported with low pregnancy rate and high OHSS risk in IVF programs due to the decreased endometrial receptivity and high ovarian reserve. The GnRH antagonist (GnRH-ant) protocol has been widely accepted as a prominent intervention to reduce the risk of OHSS, and the depot GnRH agonist (dGnRH-a) protocol are believed to improve endometrial receptivity and increase the pregnancy rate of fresh embryo transfer.Material and methodsThis study was a retrospective cohort study that included 2164 women with PCOS undergoing assisted reproductive technology (ART) treatment from January 2014 to April 2019. The two groups were matched by propensity scores with a ratio of 4:1 accounting for potential confounding factors.ResultsThe live birth per treatment cycle was higher in the dGnRH-a group than in the GnRH-ant group (58.22% vs. 41.78%, P=0.0004), the same with live birth per fresh transfer (64.42% vs. 44.64%, P=0.0045). There were no significant differences in the incidence of moderate-to-severe OHSS (4.28% vs. 2.05%, P=0.333) and the cost of COH (RMB: 7736.9 vs. 8046.54, P=0.113) between the two groups.ConclusionsOur results indicated that the dGnRH-a protocol has a higher live birth rate than GnRH-ant protocol, and the difference is mainly due to fresh embryo transfer. For safety and economic cost, the incidence of moderate-to-severe OHSS and cost of COH is similar in two groups. Nevertheless, the incidence of moderate-to-severe OHSS in the dGnRH-a group is numerically higher than GnRH-ant protocol with no statistical difference. A subsequent prospective randomized controlled study is needed to confirm these results.

Fertility outcomes in women after controlled ovarian stimulation with gonadotropin releasing hormone agonist long protocol: fresh versus frozen embryo transfer

BackgroundAlong with progress in embryo cryopreservation, especially the vitrification, freeze all strategy has become more acceptable than ever. Some studies have found comparable or higher live birth rate with frozen embryo transfer (FET) than with fresh embryo transfer(ET)in gonadotropin releasing hormone antagonist (GnRH-ant) protocol. However from our literature research, there have been no reports about live birth rate comparison between fresh ET and FET with gonadotropin releasing hormone agonist (GnRH-a) long protocol. The aim of this study is to retrospectively investigate whether patients benefit from freeze all strategy in GnRH-a protocol using real-world data.MethodsThis is a retrospective cohort study, in which women undergoing fresh ET or FET with GnRH-a long protocol at Chongqing Reproductive and Genetics Institute from January 2016 to December 2018 were evaluated. The primary outcome was live birth rate. The secondary outcomes were implantation rate, clinical pregnancy rate, pregnancy loss and ectopic pregnancy rate.ResultsA total of 7,814 patients met inclusion criteria, implementing 5,216 fresh ET cycles and 2,598 FET cycles, respectively. The demographic characteristics of the patients were significantly different between fresh ET and FET groups, except BMI. After controlling for a broad range of potential confounders including age, infertility duration, BMI, AMH, number of oocytes retrieved and of available embryos, multivariate logistic regression analysis demonstrated that there was no significant difference in clinical pregnancy rate, ectopic pregnancy rate and pregnancy loss rate between two groups (all P > 0.05). However, the implantation rate and live birth rate in fresh ET group were significantly higher than FET group (P < 0.001 and P = 0.012, respectively).ConclusionsUnder GnRH-a long protocol, compared to FET, fresh ET was associated with higher implantation rate and live birth rate in infertile patients that underwent in vitro fertilization (IVF). The freeze all strategy should be individualized and made with caution especially with GnRH-a long protocol.

Reduction in multiple pregnancy rate in donor oocyte-recipient gestational carrier (GC) in vitro fertilization (IVF) cycles in the USA with single-embryo transfer and preimplantation genetic testing.

To evaluate the utilization of single-embryo transfer (SET) and preimplantation genetic testing (PGT) in gestational carrier IVF cycles in the USA with donor oocyte and examine the impact on live birth and multiple gestation. Retrospective cohort study using the Society of Assisted Reproductive Technology (SART) clinic database of 4776 donor oocyte-recipient IVF cycles in which a GC was used. The cycles were separated into 4 groups by use of PGT and number of embryos transferred as follows: (1) PGT and single-embryo transfer (PGT-SET); (2) PGT and multiple embryo transfer (PGT-MET); (3) no PGT and SET (NoPGT-SET); (4) no PGT and MET (NoPGT-MET). Primary outcomes were live birth rate (LBR) and multiple pregnancy rate (MPR). More than one blastocyst was transferred in 48.7% (2323/4774) of the cycles. When ≥1 blastocyst was transferred, with or without the use of PGT, the MPR was 45.5% and 42.0%, respectively. In comparison, in the PGT-SET and NoPGT-SET groups, the MPR was 1.4% (8/579) and 3.3% (29/883), respectively. Live birth rates increased with the use of PGT-A and with MET. This study shows that SET, with or without PGT, is associated with a significantly reduced MPR in donor oocyte-recipient GC IVF cycles while maintaining high LBR. It also demonstrates that many infertility centers in the USA are not adhering to ASRM embryo transfer guidelines. Our findings highlight an opportunity to increase GC safety, which ultimately may lead to widened access to this increasingly restricted service outside the USA.

Adding a low-quality blastocyst to a high-quality blastocyst for a double embryo transfer does not decrease pregnancy and live birth rate.

The effect of embryo quality on clinical outcomes of assisted reproductive technology following a double transfer is not well defined, with some studies suggesting that a low-quality embryo transferred with a high-quality embryo decreases the live birth rate (LBR), compared with transferring a single high-quality embryo. Our study examined whether the quality of a second blastocyst transferred affects the outcome, controlling for the number of the available high-quality blastocysts (HQB). A historical cohort study of 2346 fresh blastocyst transfers in a single fertility clinic between 2013 and 2019. The main outcomes were pregnancy, miscarriage, live birth, and multiple gestation rates. Outcomes were compared between single embryo transfers with a high-quality blastocyst (SET-H), double embryo transfers with two HQBs (DET-HH), and transfers with one high-quality and one low-quality blastocyst (DET-HL). Outcomes were also assessed between SET and DET when only low-quality blastocysts were available. With one HQB available, DET-HL increased LBR (adjusted odds ratio [OR] 1.65, 95% CI 1.09-2.49) compared with SET-H, but increased multiple gestation rate (aOR 23.1, 95% CI 3.0-177.6). With two HQBs available, DET-HH was associated with a higher LBR (aOR 1.62, 95% CI 1.28-2.04) and lower miscarriage rate (aOR 0.56, 95% CI 0.40-0.80), but very high twin rate (aOR 49.8, 95% CI 24.3-102.1) compared with SET-H. A SET-H with at least one or more HQB available to freeze, compared with a SET-H with no other HQB available, had a higher LBR (aOR 1.69, 95% CI 1.17-2.45). When there were no HQBs available, compared with SET-L, a DET-LL had a higher live birth (aOR 3.20, 95% CI 1.78-7.703) and twin rate (aOR 3.72×1010 ) and a lower miscarriage rate (aOR 0.24, 95% CI 0.10-0.58). When there is one HQB available, transferring an additional low-quality blastocyst would only slightly increase the LBR, but significantly increase the twin rate, therefore SET should be recommended. When two or more HQBs are available, SET-H would have a reasonably good chance of success without the very high twin rate associated with DET-HH. DET-LL when compared with SET-L, would increase the LBR, but increase the risk of multiple gestation.

Effect of progesterone on hCG day-to-basal progesterone ratio on live birth rate in long agonist fresh IVF/ICSI cycles: a 5-year, single-center study of more than 10,000 cycles

Objective To investigate whether the ratio of the serum progesterone level on the day of human chorionic gonadotrophin (hCG) administration to the basal serum progesterone level (PhCG/Pbasal) is a predictor of pregnancy outcome during in vitro fertilization (IVF). Methods A total of 12,708 cycles were performed in 9747 patients between 19 and 36 years of age who were undergoing controlled ovarian stimulation from October 2011 to July 2016 for their first or second attempts at IVF followed by fresh embryo transfer (ET). hCG was administered 36 h before oocyte retrieval to trigger final oocyte maturation. The serum progesterone level was measured on menstrual cycle days 2-4 (basal progesterone, Pbasal) and on the day of hCG administration (PhCG). PhCG/Pbasal was calculated. Live birth rates were compared among various ordinal PhCG/Pbasal intervals (< 0.5, 0.5–1.0, 1.0–1.5, 1.5–2.0, 2.0–2.5, > 2.5). Results The average age of the patients recruited was 29.9 years. The average basal progesterone level was 0.8 ng/ml, while the average progesterone level on the day of hCG administration was 0.9 ng/ml. The live birth rates (according to the abovementioned ordinal PhCG/Pbasal intervals) were 47.3, 49.9, 47.8, 46.3, 45.5 and 44.0%, respectively. The live birth rates were significantly higher for patients with PhCG/Pbasal between 0.5–1.0 (OR = 1.14, 95% CI, 1.02–1.27, p = .02). Conclusions PhCG/Pbasal between 0.5-1.0 predicts a higher live birth rate in IVF. Both PhCG/Pbasal and P on hCG day is less predictive value for predicting live birth rate.

The effect of different endometrial preparations on women with polycystic ovary syndrome undergoing initial frozen embryo transfer: A historical cohort analysis.

Frozen embryo transfer is associated with a higher rate of live birth and a lower risk for ovarian hyperstimulation syndrome in women with polycystic ovary syndrome (PCOS) compared with fresh embryo transfer. The aim of this study is to assess the optimal endometrial preparation protocol for women with PCOS undergoing frozen embryo transfer. We conducted a historical cohort analysis of 1720 women with PCOS who underwent the "freeze-all" strategy between August 2014 and August 2017 because of their high risk for ovarian hyperstimulation syndrome. Three endometrial preparation protocols were used: natural cycle (NC; n=191), which relies on the dominant follicle to secrete estrogen that then promotes endometrial growth; ovarian stimulation (OS; n=96), which induces follicle growth using low doses of human menopausal gonadotropin; and hormone replacement (HRT; n=1433), which uses exogenous estradiol to promote endometrial growth. The primary outcome was live birth. For women who received a single embryo transfer, the live birth rates for the NC, OS, and HRT groups were 62.4%, 65.0%, and 52.2%, respectively. The live birth rate in the HRT group was significantly lower than that seen in the OS and NC groups (P=.009). The clinical pregnancy rates of the three groups were 72.3%, 73.8%, and 64.9%, respectively; this difference did not reach statistical significance (P=.071). The rate of live birth with the NC and OS regimens was higher than with the HRT protocol in women with PCOS who undergo single-blastocyst frozen embryo transfer.

Should the modified natural cycle protocol for frozen embryo transfer be modified? A prospective case series proof of concept study

ObjectiveModified natural cycles for frozen embryo transfer utilize an ovulation trigger which assists in embryo transfer scheduling and simplifies cycle monitoring. There have been conflicting results with this protocol and modifications may be sought. We wanted to ascertain whether a modified natural protocol for frozen embryo transfer without triggered ovulation but with luteal progesterone support disconnecting the timing of embryo transfer from the timing of the LH surge can achieve a high pregnancy rate. Study designCandidates for frozen embryo transfer of 48-h cleavage cell embryos were recruited from May 2016 to April 2018. The patients were monitored for endometrial growth, follicle formation and estradiol, progesterone, and LH hormone levels. After meeting the predetermined criteria, embryo transfer was scheduled. The patients began progesterone treatment 48 h before embryo transfer, regardless of identification of the LH surge if ovulation had not commenced. The predetermined primary outcome was the biochemical pregnancy rate while the secondary outcome included the clinical pregnancy rate and the ongoing pregnancy rate. Patients were monitored to the eighth week of pregnancy, but data was collected from the medical records to provide the live birth rate as well. ResultsFifty-six women were screened. Eleven women declined or did not meet the inclusion criteria. Three had anovulatory cycles and were excluded. Forty-two women were included in the statistical analysis. The implantation rate was 42.9 % [95 %CI 29.3 %–56.4 %). Of the 42 participants, 25 (59.5 %) conceived [95 % CI 44.0 %–75 %]. Two pregnancies ended in first trimester miscarriage leaving 23 (54.7 %) ongoing pregnancies [95 % CI 39.1 %–70.5 %]. One patient experienced a late abortion such that the live birth rate was 22 of 42 patients or 52.4 % [95 % CI 36.4 %–68.0 %]. ConclusionThe proposed modified natural protocol which utilizes progesterone luteal support but does not trigger ovulation, maintains a high pregnancy rate while providing flexibility regarding the day of transfer disconnected from the day of the LH surge. This was a prospective, proof of concept study. This protocol may be suitable for smaller or public in-vitro fertility units whose resources are limited and facilities are not available daily. The high pregnancy and live birth rate that we found provides confidence that this protocol can be part of the armament of protocols the clinician may offer to his patients. Larger studies should confirm these findings.

Effect of Age and Embryo Morphology on Live Birth Rate After Transfer of Unbiopsied Blastocysts.

Objective:To determine the rate of live birth per blastocyst based on morphology and oocyte age using data from a single center.Methods:This is a mathematical analysis and model building study of autologous blastocyst stage embryo transfers at a University-affiliated center. A total of 448 blastocyst stage embryos were transferred in 244 fresh and frozen embryo transfers from May 2015 through April 2018. Blastocyst morphology was divided into good, fair, and poor overall morphology grades. Each embryo transfer was modeled as an equation equating the sum of the unknown live birth rates of the transferred embryos to the number of live births that resulted. The least squares solution to the system of embryo transfer equations was determined using linear algebra.Results:Trophectoderm morphology was a better predictor of live birth rate than inner cell mass morphology. Embryos graded AA/AB/BA (good) had the highest live birth rates followed by BB/CB (fair), and BC/CC (poor). In our youngest age group (25-32 years) live birth rates per embryo were 51% for good, 39% for fair, and 25% for poor quality embryos. In our oldest age group (40-44 years) the live birth rates per embryo were 22% for good, 14% for fair, and 8% for poor quality embryos.Conclusions:These techniques can help analyze small datasets such as those from individual clinics to aid in determining the ideal number of embryos to transfer to achieve live birth while limiting the risk of multiple gestations.

Different Timing of Adjuvant Low Dose hCG and GnRH Agonist Trigger Protocol, in OHSS High-Risk Patient with Peak E2 Level &lt;4000 pg/mL

OBJECTIVE: The aim of the study is to compare the live birth rates between 1,500 I.U. of Human chorionic gonadotropin at the time of Gonadotropin-releasing hormone agonist trigger day or 35-36 h later on the oocyte pick-up day, without affecting the risk of significant ovarian hyperstimulation syndrome development in high-risk patients with peak E2 level &lt;4,000 pg/mL STUDY DESIGN: This single-center prospective cohort study encompassed the period from March 2016 to March 2018 year. A total of 216 patients entered for final analysis, underwent a flexible antagonist protocol, intracytoplasmic sperm injection, and embryo transfer on the 3rd or 5th day in autologous cycles. Patients were randomized in one of two groups: Group A- Dual trigger group - 1,500 IU of Human chorionic gonadotropin at the time of Gonadotropin-releasing hormone agonist trigger day and Group B- 1,500 IU of Human chorionic gonadotropin 35-36 h later, on the oocyte pick-up day. To compare the two groups, we used nonparametric and parametric statistical tests. Significant differences were considered all values of p&lt;0.05. RESULTS: There is no significant difference between the two (A vs B) groups according to the average number of retrieved oocytes (13.08 vs 14.41 p=0.08), M II oocytes (10.5 vs 10.95 p=0.46), GV (1.24 vs 1.52 p=0.09, the fertility rate (68.46% vs 64.04% p=0.07). The dual trigger group (A) had a significantly higher live birth rate (62.29% vs 42.37% p&lt;0.05) compared with the Gonadotropin-releasing hormone-a trigger group (B). There were no cases of moderate or severe ovarian hyperstimulation syndrome in both groups. CONCLUSION: Our study shows that in hyper responders where the E2 peak is &lt;4,000 pg/mL, the two approaches to the final oocyte maturation trigger have a correct outcome of the results, both in terms of the results from the in vitro fertilization and the low risk of ovarian hyperstimulation syndrome appearance.

Progesterone Intramuscularly or Vaginally Administration May Not Change Live Birth Rate or Neonatal Outcomes in Artificial Frozen-Thawed Embryo Transfer Cycles.

BackgroundsPrevious studies suggested that singletons from frozen-thawed embryo transfer (FET) were associated with higher risk of large, post-date babies and adverse obstetrical outcomes compared to fresh transfer and natural pregnancy. No data available revealed whether the adverse perinatal outcomes were associated with aberrantly high progesterone level from different endometrium preparations in HRT-FET cycle. This study aimed to compare the impact of progesterone intramuscularly and vaginally regimens on neonatal outcomes in HRT-FET cycles.MethodsA total of 856 HRT-FET cycles from a fertility center from 2015 to 2018 were retrospectively analyzed. All patients had their first FET with two cleavage-staged embryos transferred. Endometrial preparation was performed with sequential administration of estrogen followed by progesterone intramuscularly 60 mg per day or vaginal gel Crinone 90 mg per day. Pregnancy outcomes including live birth rate, singleton birthweight, large for gestational age (LGA) rate, small for gestational age (SGA) rate, and preterm delivery rate were analyzed. 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.ResultsNo 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 singleton birthweight (p = 0.744), preterm delivery rate (Adjusted OR 1.920, 95% CI 0.603, 6.11, p = 0.269), SGA (Adjusted OR 0.227, 95% CI 0.027, 1.934, p = 0.175), and LGA rate (Adjusted OR 0.862, 95% CI 0.425, 1.749, p=0.681) 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 ≤41.82 pmol/L in HRT-FET cycles when progesterone was intramuscularly delivered (Adjusted OR 1.690, 95% CI 1.002, 2.849, p = 0.049). But singleton birthweight, preterm delivery rate, SGA and LGA rate were not different between these two groups.ConclusionsRelatively higher serum progesterone level induced by intramuscular regimen did not change live birth rate or neonatal outcomes compared to vaginal regimen. Monitoring serum progesterone level and optimizing progesterone dose of intramuscular progesterone as needed in HRT-FET cycles has a role in improving live birth rate without impact on neonatal outcomes.

Vitamin D supplementation prior to in vitro fertilisation in women with polycystic ovary syndrome: a protocol of a multicentre randomised, double-blind, placebo-controlled clinical trial

IntroductionPolycystic ovary syndrome (PCOS) is one of the leading causes of female infertility, affecting around 5% of women of childbearing age in China. Vitamin D insufficiency is common in women...

Adjuvant Vaginal Use of Sildenafil Citrate in a Hormone Replacement Cycle Improved Live Birth Rates Among 10,069 Women During First Frozen Embryo Transfers.

PurposeTo investigate the effects of sildenafil citrate (SC) on live birth rates (LBR) during women undergoing their first frozen embryo transfers (FET) with hormone replacement therapy (HRT).Patients and MethodsThis retrospective cohort study included a total of 10,069 infertile women with adequate endometrial thickness (≥7 mm when progesterone was initiated) in their first FET cycle with hormone replacement therapy. Women received either vaginal SC or no adjuvant during their first transfer cycle depending on patient or physician preference. In the sildenafil group, 1098 women underwent HRT FET with adjuvant vaginal use of SC, and 8971 women were included as controls. The primary outcome measure was LBR, defined as the likelihood of live birth per transfer cycle. Endometrial thickness (EMT), implantation, chemical pregnancy, clinical pregnancy, miscarriage, ongoing pregnancy, birth weight and preterm delivery (PTB) were also recorded.ResultsBaseline characteristics were comparable between the two groups. In the crude analysis, the unadjusted LBR was significantly higher in the vaginal SC group (scHRT-FET) than in the control group (HRT-FET) (40.3% vs 36.1%). After adjustment for 12 pregnancy-related confounding factors, logistic regression analysis showed that LBR remained significantly higher in the scHRT-FET group than in the HRT-FET group (adjusted odds ratio [aOR] 1.31, 95% confidence interval [CI] 1.14–1.49). Furthermore, after adjustment, the ongoing pregnancy rate was significantly higher (aOR 1.29, 95% CI 1.13–1.47), and the miscarriage rate was significantly lower (aOR 0.58, 95% CI 0.43–0.77), in the scHRT-FET group compared to the HRT-FET group. Adjuvant vaginal use of SC did not increase the endometrial thickness and had no significant effect on birth weight or PTB.ConclusionAdjuvant vaginal use of SC in HRT FET was associated with higher LBR and improved pregnancy outcomes in an infertile population with adequate endometrial thickness. The beneficial effect of SC may be due not to an increase in EMT but instead to improve endometrial blood flow and receptivity, which might merit clinicians’ attention for improving general IVF practices.

Effect of culture conditions and method of conception on mouse live birth rate

To understand in a mouse model whether there are differences in the decidua and live birth rate after transfer of blastocysts generated by invitro fertilization (IVF) or by superovulation with spontaneous mating into unstimulated recipients. Animal experiment. University-affiliated tertiary hospital. Mice. IVF embryos were generated and cultured in either Whitten medium (WM, suboptimal conditions) and 20% O2 or KSOM medium with amino acids (KAA, optimal conditions) and 5% O2. The control blastocysts from superovulated mice were flushed out of the uterus 3.5 days (E3.5) after mating (FB group). The resulting blastocysts were transferred to nonsuperovulated CF1 recipients mated to vasectomized males. To understand whether anomalies of decidua were present, the expression of genes involved in decidual development and inflammation was analyzed at E7.5 and E18.5. Similarly, immunostaining was used to evaluate whether the pathways involved in activation of mTORC1 (p-S6) and Cox2 signaling (Cox 2 staining) were altered. Live birth rate, gene expression, and immunostaining of decidua. Implantation rates at E7.5 were similar, but invivo embryos (FB groups) were predicted to result in live births 3.3 times higher (2.2-5.1) and 6.6 times higher (4.7-9.3) compared with optimal and suboptimal cultures, respectively. Expression of genes involved in decidual development and inflammation or localization and intensity of staining for p-S6 (mTOR pathway), or inflammation (Cox 2 pathway) were not different among the groups. The predicted live birth rate was decreased in mouse embryos generated by IVF compared with embryos generated by mating, whereas the implantation rate was not different. Suboptimal culture conditions resulted in lower birth rate. We did not find evidence of abnormalities in decidualization that could explain these findings. These data indicate that blastocysts cultured in stressful conditions are less competent, suggesting that decreasing the number of embryonic manipulations may result in higher live birth rates.

Spontaneous pregnancy rate following surgery for deep infiltrating endometriosis in infertile women: The impact of the learning curve

ObjectivesTo determine whether the surgical learning curve impact the spontaneous pregnancy rate in infertile patients undergoing removal of deep infiltrating endometriosis Material and MethodsSingle center retrospective study including the first 50 consecutive infertile women suffering from deep infiltrating endometriosis and referred to a single surgeon. All patients underwent laparoscopic removal of deep endometriosis lesions. The study population was stratified in two subgroups, namely the early group (including the first 25 cases) and the late group (comprising the 25 subsequent cases). Pregnancy and live birth rates, surgical morbidity and clinical recurrence rate were compared between study groups. ResultsOverall, spontaneous pregnancy rate (40 % in the early group versus 56 % in the late group, p = 0.25), live birth rate (40 % versus 44 %, p = 0.77) and clinical recurrence rate (16 % versus 4%, p = 0.16) did not significantly differ between the study groups. Logistic regression analysis revealed that ASRM stage, EFI score, and body mass index were the only significant prognostic factors of postoperative spontaneous fertility. ConclusionSurgical resection of deep infiltrating endometriosis in infertile women is associated with high spontaneous pregnancy and live birth rates. The surgeon’s learning curve does not impact postoperative fertility outcomes.

Differential impact of controlled ovarian hyperstimulation on live birth rate in fresh versus frozen embryo transfer cycles: a Society for Assisted Reproductive Technology Clinic Outcome System study

To study the impact of both controlled ovarian hyperstimulation (COH) length and total gonadotropin (GN) dose individually and in concert on live birth rates (LBR) in both fresh and freeze-all invitro fertilization embryo transfer (IVF-ET) cycles. Historical cohort study. Not applicable. The U.S. national database from the Society of Assisted Reproductive Technology Clinic Outcome Reporting System from 2014 to 2015 was used to identify patients undergoing autologous GN stimulation IVF cycles with the use of GnRH antagonist-based suppression protocols where a single embryo transfer was performed as part of a fresh IVF-ET cycle (fresh, n = 14,866) or the first frozen embryo transfer after a freeze-all cycle (frozen, n = 2,964), and not including preimplantation genetic testing cycles. The patients' demographic and cycle characteristics, duration of COH, total GN dose, and pregnancy outcomes were extracted. Binomial regression models estimated trend and relative risk of live birth with respect to days of stimulation and total GN dose singularly, and after adjustment for a priori confounders including age, parity, body mass index, diagnosis, and maximum follicle-stimulating hormone in both fresh and frozen embryo transfer cycles. Both days of stimulation and total GN dose were then added to the multivariate model to show whether they were independently associated with LBR. Not applicable. Live birth rate. In both fresh and frozen cycles, length of COH was significantly associated with total GN dose. On univariate analysis, LBR decreased significantly with increasing length of stimulation and increasing total GN dose in both fresh and frozen cycles. On multivariable analysis including both days of stimulation and total GN dose, days of stimulation was no longer significantly correlated with LBR, whereas total GN dose remained significantly correlated with LBR in fresh cycles only. When total GN doses ranging from <2,000 IU through 5,000 IU to >5,000 IU were compared, a significant improvement in live birth rate was noted with lower total GN doses. Specifically, GN doses <2,000 IU had a 27% higher rate of live birth compared with GN dose >5,000 IU. For GN dose groups up to 4,000 IU, the estimated effect on LBR was similar. There was a marginal improvement (13%) in LBR with GN doses of 4,000 IU to 5,000 IU compared with >5,000 IU. When the multivariate model was applied to the frozen cycles, neither total GN dose nor days of stimulation was significantly associated with LBR. High total GN dose but not prolonged COH is associated with decreasing LBRs in fresh cycles, whereas neither factor significantly affects LBR in frozen cycles. Consideration should be given to minimizing the total GN dose when possible in fresh autologous cycles, either by decreasing the daily dose or by limiting the length of stimulation to improve LBRs. In freeze-all cycles, the use of higher GN doses does not seem to adversely affect the LBR of the first frozen embryo transfer. High total GN dose likely exerts a negative impact on the endometrium and/or oocyte/embryo unrelated to the length of stimulation. The differential effect of total GN dose on LBR in fresh and frozen cycles may imply a greater impact exerted on the endometrium rather than the oocyte.

Endometrial thickness after ovarian stimulation with gonadotropin, clomiphene, or letrozole for unexplained infertility, and association with treatment outcomes

To study the association of endometrial thickness (EMT) with live birth rates (LBR) in ovarian stimulation with intrauterine insemination (OS-IUI) treatments for unexplained infertility. Prospective cohort analysis of the Reproductive Medicine Network's Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation (AMIGOS) randomized controlled trial. Multicenter randomized controlled trial. A total of 868 couples with unexplained infertility (n=2,459 cycles). OS-IUI treatment cycles (n = 2,459) as part of the AMIGOS clinical trial. Live birth rates; unadjusted and adjusted risk ratios (RR) for live birth by EMT category, calculated using generalized estimating equations. The overall mean EMT on day of human chorionic gonadotropin administration in cycles with a live birth was significantly greater than in those without. Compared to the referent EMT group of 9 to 12 mm, the unadjusted RR for live birth for the EMT groups of ≤5 and 6-8 were 0.48 and 0.92, respectively. The test for trend indicated evidence of decreasing LBR with decreasing EMT. After adjustment for ovarian stimulation medication, a linear trend was no longer supported. Stratified analyses revealed no differences in associations by treatment group. In OS-IUI for unexplained infertility, higher LBR are observed with increasing EMT; however, EMT is not significantly associated with LBR when adjusted for OS treatment type. Appreciable LBR are seen at all EMT, even those of ≤5 mm, suggesting that OS-IUI cycles should not be canceled for thin endometrium. NCT01044862.