ULTRASOUND IMAGING PREDICTS ENDOMETRIAL RECEPTIVITY – A DECREASE IN ENDOMETRIAL THICKNESS (COMPACTION) PRIOR TO EMBRYO TRANSFER IS ASSOCIATED WITH AN INCREASE IN CLINICAL PREGNANCY RATE IN SYNTHETIC FROZEN EUPLOID IVF CYCLES

Abstract Study question Does GCSF by intrauterine route leads to better result in the treatment of thin endometrium as compared to GCSF by the subcutaneous route, in IVF-ICSI Cycles? Summary answer Yes, GCSF by intrauterine route leads to better result in the treatment of thin endometrium as compared to subcutaneous-GCSF, in ART Cycles? What is known already GCSF, is a member of the colony stimulating factor family of cytokines and growth factors. GCSF receptors are expressed in high concentration on dominant follicle, particularly at preovulatory stage.The endometrium also shows an increased expression of these receptors. GCSF concentration rises in the follicular fluid at the same time. Serum levels of GCSF are found to be in direct correlation with levels of GCSF in follicular fluid. Serum levels increase progressively from the day the embryo-transfer to the day of implantation. GCSF has been found to be beneficial in patients with thin endometrium and recurrent implantation failure. Study design, size, duration This was a RCT conducted between 2018–2019. 30 patients with thin endometrium were enrolled in each group. In either group, GCSF was given if endometrium was less than 7mm on day 14, maximum of two doses were administered. Patients undergoing frozen embryo transfer were recruited in the study, after meeting the inclusion and exclusion criteria. Primary outcome measured was increase in endometrium thickness and the secondary outcome was the clinical pregnancy rate and abortion-rate. Participants/materials, setting, methods 60 patients with thin endometrium were randomly divided into two groups. Group A: Inj. GCSF (300 mcg/1 ml) subcutaneously on Day 14 onwards alternate days for two doses. Group B: Inj. GCSF (300 mcg/1 ml) instilled slowly into the uterine cavity using an intrauterine insemination (IUI) catheter under USG guidance. Endometrial thickness was assessed after 48 h. If endometrial thickness was found to be < 7 mm, a second infusion of GCSF was carried out. Main results and the role of chance In the subcutaneous group (group-A) the mean endometrial thickness before GCSF injection was 5.8 ± 0.6 mm and, after injection it increased to 6.9 ± 0.4 mm. Similarly, in the intrauterine group (group-B) the mean endometrial thickness before GCSF was 5.9 ± 0.7 which increased to a mean of 7.9 ± 0.5 after GCSF instillation. The difference between endometrial thickness before and after intrauterine infusion of GCSF was more than that in the subcutaneous group. In group-A, 08 patients conceived out of 30 patients ( clinical pregnancy rate 26.6%) and in group B 11 conceived out of 30 patients in whom GCSF was instilled intrauterine (pregnancy rate 36.6%). Thus, there was a difference in the clinical pregnancy rate in the two groups, the intrauterine group yielding a higher clinical pregnancy rate, but it was not statistically significant. Because of the thin endometrium, we found an abortion rate of 25% (2/8) in the subcutaneous-GCSF group, and an abortion rate of 18% (2/11) in the intrauterine GCSF group. Limitations, reasons for caution There are few potential limitations because of the small sample size. Confounders such as obesity, smoking and alcohol intake, presence of adenomyosis and endometriosis, were not taken into consideration. Though prevalence of obesity is usually low in Indian women. Habits of smoking and alcohol are exceedingly uncommon in Indian women. Wider implications of the findings: Use of GCSF plays an important role in management of patients of thin endometrium undergoing embryo transfer. It is an easily available and economical preparation in developing countries and the intrauterine instillation of GCSF can be easily practiced in an ART unit with good results in resistant thin endometrium patients. Trial registration number Not applicable

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P–151 Correlation between the first euploid frozen-thawed blastocyst embryo transfer (FBT) and the subsequent euploid FBT outcome originating from the same cohort of oocytes

Human Reproduction ◽

10.1093/humrep/deab130.150 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

R Abalı ◽

F K Boynukalın ◽

M Gültomruk ◽

Z Yarkiner ◽

M Bahçeci

Keyword(s):

Regression Analysis ◽

Pregnancy Rate ◽

Pregnancy Outcome ◽

Embryo Transfer ◽

Live Birth ◽

Endometrial Thickness ◽

Clinical Pregnancy ◽

Clinical Pregnancy Rate ◽

Ongoing Pregnancy ◽

Ongoing Pregnancy Rate

Abstract Study question Does the outcome of the first euploid frozen-thawed blastocyst embryo transfer affect the subsequent euploid FBT originating from the same cohort of oocytes? Summary answer The clinical pregnancy rate and ongoing pregnancy rate of the subsequent FBT are higher if a clinical pregnancy was attained in the first euploid FBT. What is known already Numerous factors including patient, cycle and embryological characteristics affect the outcome of an IVF treatment cycle. There is no data available whether the outcome of euploid FBT has an impact on the outcome of the subsequent euploid FBT of embryos originating from the same cohort of retrieved oocytes. Study design, size, duration The study enrolled cycles preimplantation genetic test for aneuploidy (PGT-A) performed between January 2016 and July 2019 at the Bahceci Fulya IVF Center. A total of 1051 patients with single euploid FBT were evaluated and resulted live birth (n = 589, live birth rate (LBR): 56%(589/1051)), miscarriage (n = 100, miscarriage rate (MR): 14.5% (100/689)) and no clinical pregnancy (n = 362, 34,4%, (362/1051)). 159 FBT after the first single euploid FBT originating from the same cohort of oocytes were analyzed. Participants/materials, setting, methods Second euploid FBT cycle after first FBT with a clinical pregnancy were compared to frozen-thawed cycles after a without a pregnancy. Logistic regression analysis was utilized to adjust for potential confounders including female age, body mass index, embryo quality, day of embryo frozen, number previous failed attempt, number of previous miscarriage, endometrial thickness, outcome of the first euploid FBT. Main results and the role of chance The pregnancy outcome from the first euploid FBT in the study group was resulted live birth (25.1%, (40/159)), miscarriage (15.7%, (25/159)) and no clinical pregnancy (59.1%, (94/159). The pregnancy outcome of the subsequent euploid embryo transfer from the same oocyte cohort was clinical pregnancy rate (CPR): (67.3%, (107/159) ongoing pregnancy rate (OPR) (52.2% (83/159) and MR (22.4%, (24/107)). The CPR in the subsequent euploid FBT was 80% (52/65) among patients who achieved a clinical pregnancy in the first euploid FBT and 58.5% (55/94) of those who did not (p = 0.0045). The OPR in the subsequent euploid FBT was 64.6% (42/65) among patients who achieved a clinical pregnancy in first euploid FBT and 43.6% (41/94) of those who did not (p = 0.009). On a multivariate regression analysis, clinical pregnancy in the first euploid FBT was a significant independent predictor for a pregnancy in the subsequent FBT transfer (p = 0.003). Limitations, reasons for caution The limitation of the study is in the retrospective nature of the study. As the PGT-A strategy significantly decreases number of transferable embryos, the sample size of the study is limited. Wider implications of the findings: Identifying predictive factors for the success of euploid FBT is important. These can help physicians while counseling patients regarding the outcome of the previous euploid FBT. Trial registration number NA

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The function of metformin in endometrial receptivity (ER) of patients with polycyclic ovary syndrome (PCOS): a systematic review and meta-analysis

Reproductive Biology and Endocrinology ◽

10.1186/s12958-021-00772-7 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Lifang Yuan ◽

Hongbo Wu ◽

Weiyu Huang ◽

Yin Bi ◽

Aiping Qin ◽

...

Keyword(s):

Pregnancy Rate ◽

Large Scale ◽

Endometrial Thickness ◽

Meta Analysis ◽

Resistance Index ◽

Endometrial Receptivity ◽

Small Sample ◽

Clinical Pregnancy ◽

Clinical Pregnancy Rate ◽

Miscarriage Rate

Abstract Background This meta-analysis summarizes evidence from studies using metformin (Met) to improve endometrial receptivity (ER) in women with PCOS. Methods Following the PRISMA protocol, we conducted a comprehensive search of academic literature from various databases, including PubMed, EMbase and Cochrane libraries. Studies published in English before Jan 27, 2021, were recruited for primary screening. Data on endometrial thickness (EMT), endometrial artery resistance index (RI), clinical pregnancy rate (CPR) and miscarriage rate (MR) were extracted and analyzed. Results Sixty-two eligible studies that included 6571 patients were evaluated in this meta-analysis. Primary indicators are EMT and endometrial aetery RI; secondary indicators include the clinical pregnancy rate and miscarriage rate. Metformin significantly increased EMT (SMD = 2.04, 95% CI (0.96,3.12),P = 0.0002) and reduced endometrial artery RI compared to the non-Met group (SMD = − 2.83, 95% CI: (− 5.06, − 0.59), P = 0.01). As expected, metformin also improved CPR and reduced MR in PCOS patients as a result, clinical pregnancy rate (risk ratio [RR] = 1.26, 95% CI: 1.11–1.43, P = 0.0003), and miscarriage rate (RR = 0.73, 95% CI:0.58–0.91, P = 0.006). Conclusion Metformin may improve endometrial receptivity (ER) in PCOS patients by increasing EMT and reducing endometrial artery RI. However, the level of most original studies was low, with small sample sizes. More large-scale, long-term RCTs with rigorous methodologies are needed.

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Endometrial thickness measurements among Asherman syndrome patients prior to embryo transfer

Human Reproduction ◽

10.1093/humrep/deaa273 ◽

2020 ◽

Vol 35 (12) ◽

pp. 2746-2754

Author(s):

Peter Movilla ◽

Jennifer Wang ◽

Tammy Chen ◽

Blanca Morales ◽

Joyce Wang ◽

...

Keyword(s):

Pregnancy Rate ◽

Embryo Transfer ◽

Conflicts Of Interest ◽

Endometrial Thickness ◽

Multivariable Analysis ◽

Small Sample ◽

Clinical Pregnancy ◽

Clinical Pregnancy Rate ◽

The Mean ◽

The Impact

Abstract STUDY QUESTION Is there an association between endometrial thickness (EMT) measurement and clinical pregnancy rate among Asherman syndrome (AS) patients utilizing IVF and embryo transfer (ET)? SUMMARY ANSWER EMT measurements may not be associated with successful clinical pregnancy among AS patients undergoing IVF. WHAT IS KNOWN ALREADY Clinical pregnancy rate after IVF is significantly lower in patients with a thin endometrium, defined as a maximum EMT of <7 mm. However, AS patients often have a thin EMT measurement due to intrauterine scarring, with a paucity of data and no guidance on what EMT cutoff is appropriate when planning an ET among these patients. STUDY DESIGN, SIZE, DURATION This is a retrospective cohort study of 45 AS patients treated at a specialized advanced hysteroscopic clinic from 1 January 2015, to 1 March 2019. PARTICIPANTS/MATERIALS, SETTING, METHODS Review of EMT measurements prior to a total of 90 ETs, among 45 AS patients. The impact of the maximum EMT measurement prior to ET on clinical pregnancy rate was analyzed. MAIN RESULTS AND THE ROLE OF CHANCE A total of 25/45 (55.6%) AS patients ultimately went on to have ≥1 clinical pregnancy following a mean ± SD of 2.00 ± 1.26 ET attempts. There was a total of 90 ETs among the 45 AS patients, with 29/90 (32.2%) ETs resulting in a clinical pregnancy. Younger patient age (P = 0.05) and oocyte donation (P = 0.01) were the only variables identified to be significant predictors for a positive clinical pregnancy outcome on bivariate analysis. The mean EMT measurement prior to all ETs among AS patients was 7.5 ± 1.6 mm. EMT measurement prior to ET did not predict a positive clinical pregnancy on either bivariate (P = 0.84) or multivariable analysis (odds ratio 0.91, P = 0.60). 31.8% of EMT measurements measured <7.0 mm. In this small cohort, no difference in the clinical pregnancy rate was detected when comparing ETs with EMT measurements of <7.0 mm versus ≥7.0 mm (P = 0.83). The mean EMT measurement decreased with increasing AS disease severity; 8.0 ± 1.6 mm for mild disease, 7.0 ± 1.4 mm for moderate disease and 5.4 ± 0.1 mm for severe disease. LIMITATIONS, REASONS FOR CAUTION Our small sample size limits our ability to draw any definitive conclusions. In addition, patients utilized various infertility clinics. This limits our ability to evaluate the consistency of EMT measurements and the IVF care that was received. WIDER IMPLICATIONS OF THE FINDINGS EMT measurement cutoff values should be used with caution if canceling a scheduled ET in AS patients. STUDY FUNDING/COMPETING INTEREST(S) This study was not funded. K.I. reports personal fees from Karl Stroz and personal fees from Medtronics outside the submitted work. The other authors have no conflicts of interest. TRIAL REGISTRATION NUMBER N/A.

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The impact of endometrial thickness change after progesterone administration on pregnancy outcome in patients transferred with single frozen-thawed blastocyst

Reproductive Biology and Endocrinology ◽

10.1186/s12958-019-0545-0 ◽

2019 ◽

Vol 17 (1) ◽

Cited By ~ 7

Author(s):

Zhiqin Bu ◽

Xinhong Yang ◽

Lin Song ◽

Beijia Kang ◽

Yingpu Sun

Keyword(s):

Pregnancy Rate ◽

Pregnancy Outcome ◽

Embryo Transfer ◽

Endometrial Thickness ◽

Clinical Pregnancy ◽

Clinical Pregnancy Rate ◽

Natural Cycle ◽

Thickness Change ◽

The Impact ◽

Day Of Embryo Transfer

Abstract Background The aim of this study was to explore the impact of endometrial thickness change after progesterone administration on pregnancy outcome in patients transferred with single frozen-thawed blastocyst. Methods This observational cohort study included a total of 3091 patients undergoing their first frozen-thawed embryo transfer (FET) cycles between April 2015 to March 2019. Endometrial thickness was measured by trans-vaginal ultrasound twice for each patient: on day of progesterone administration, and on day of embryo transfer. The change of endometrial thickness was recorded. Results Regardless of endometrial preparation protocol (estrogen-progesterone/natural cycle), female age, body mass index (BMI), and infertility diagnosis were comparable between patients with an increasing endometrium on day of embryo transfer and those without. However, clinical pregnancy rate increases with increasing ratio of endometrial thickness. Compared with patients with Non-increase endometrium, those with an increasing endometrium on day of embryo transfer resulted in significantly higher clinical pregnancy rate (56.21% vs 47.13%, P = 0.00 in estrogen-progesterone cycle; 55.15% vs 49.55%, P = 0.00 in natural cycle). Conclusions In most patients, endometrial thickness on day of embryo transfer (after progesterone administration) increased or kept being stable compared with that on day of progesterone administration. An increased endometrium after progesterone administration was associated with better pregnancy outcome.

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P–359 Blastocyst quality, transfer difficulty and endometrial thickness affect clinical pregnancy after frozen embryo transfer (FET) of euploid blastocysts in the upper uterine cavity

Human Reproduction ◽

10.1093/humrep/deab130.358 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

A Bayram ◽

N D Munck ◽

A Abdala ◽

I Elkhatib ◽

A El-Damen ◽

...

Keyword(s):

Pregnancy Rate ◽

Embryo Transfer ◽

Pregnancy Outcomes ◽

Endometrial Thickness ◽

Uterine Cavity ◽

Small Sample ◽

Clinical Pregnancy ◽

Clinical Pregnancy Rate ◽

Endometrial Preparation ◽

Blastocyst Quality

Abstract Study question Which factors affect the clinical pregnancy rate (CPR) after single euploid frozen embryo transfers (FET), when the blastocyst is transferred in the upper uterine cavity area? Summary answer Blastocyst quality, embryo transfer difficulty and endometrial thickness affect the CPR in FET. What is known already There is a limited understanding of the factors affecting success rates after FET. The most important factors influencing implantation rates are patient characteristics, type of endometrial preparation, embryo quality and transfer difficulty. It has been shown that the position of the euploid blastocyst, measured as distance from the fundus (DFF) of the uterine cavity (mm), affects the implantation potential. Although the ideal location within the uterine cavity is still being debated in very heterogeneous patient populations, most studies have found that the highest pregnancy rates are obtained when the embryo is placed in the upper area of the uterine cavity. Study design, size, duration This single center retrospective cohort study included a total of 603 single euploid FET cycles, in the upper half of the uterine cavity, between January 2019 and November 2020 in ART Fertility Clinic Abu Dhabi, UAE. Participants/materials, setting, methods Trophectoderm biopsy samples were subjected to Next Generation Sequencing to screen the ploidy state. Vitrification and warming were performed using the Cryotop method (Kitazato, Biopharma). The full length of the uterine cavity and the longitudinal distance between the fundal endometrial surface and the air bubble after transfer were measured. Main results and the role of chance The patients were on average 33.9 (19–46) years old. The FET was performed in a natural cycle (NC) (n = 278) or hormone replacement therapy (HRT) (n = 325). Of the 603 transfers which had been performed in the upper half of the uterus, 412 (68.3%) resulted in a pregnancy and 311 (51.5%) in a clinical pregnancy. After bivariate analysis, the clinical pregnancy rate was significantly higher for high quality blastocysts (grade 1–2 versus 3–4) (p < 0.001), after easy embryo transfers (p = 0.001) and for higher endometrial thickness (p = 0.027). After performing a multivariate logistic regression analysis to consider the effect of all explanatory variables (age, Anti Müllerian hormone, body mass index, endometrial thickness, quality of the blastocyst, difficulty of the transfer [requirement of additional instrumentation], presence of mucus or blood on the transfer catheter, day 5 or day 6 biopsy, FET endometrial preparation), the clinical pregnancy was affected by the endometrial thickness: OR 1.20 [1.05–1.37], p = 0.007; transfer difficulty: OR 0.44 [0.25–0.79], p = 0.006; blastocyst quality 3: OR 0.38 [0.18–0.79], p = 0.01 and blastocyst quality 4: OR 0.15 [0.06–0.37], p < 0.0001. Age did not affect the clinical pregnancy after transferring a single euploid blastocyst: OR 1.03 [1.00–1.06], p = 0.052. Limitations, reasons for caution The limitation of this study was its retrospective nature and the small sample size. Other parameters may be important in live birth outcomes. Wider implications of the findings: Optimization of clinical pregnancy outcomes after FET depends on multiple factors. Even after transfer of euploid blastocysts in the upper uterine cavity, the endometrial thickness, transfer difficulty and blastocyst quality will still affect the clinical pregnancy outcomes. Trial registration number NA

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Endometrial thickness is associated with the clinical pregnancy rate in unstimulated menstrual cycles – a study based on Natural Cycle IVF

10.26226/morressier.5912d9ead462b8029238625e ◽

2017 ◽

Author(s):

Michael von Wolff

Keyword(s):

Pregnancy Rate ◽

Endometrial Thickness ◽

Clinical Pregnancy ◽

Clinical Pregnancy Rate ◽

Natural Cycle ◽

Menstrual Cycles ◽

Natural Cycle Ivf

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P–371 Clinical value assessment between endometrial receptivity array and immune profiling in patients with implantation failure

Human Reproduction ◽

10.1093/humrep/deab130.370 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

Y Dong ◽

Y Jia ◽

Y Sha ◽

L Diao ◽

S Cai ◽

...

Keyword(s):

Pregnancy Rate ◽

Pregnancy Outcomes ◽

Statistical Difference ◽

Endometrial Receptivity ◽

Clinical Pregnancy ◽

Clinical Pregnancy Rate ◽

Implantation Failure ◽

Clinical Value ◽

Evaluation Approaches ◽

Immune Profiling

Abstract Study question To evaluate whether the pregnancy outcomes could be improved in implantation failure patients by endometrial receptivity array, endometrial immune profiling, or a combination of both. Summary answer There was no statistical difference between different endometrial receptivity evaluation and treatment in improving the clinical pregnancy rate. What is known already Both endometrial receptivity array and endometrial immune profiling were promised to improve the endometrial receptivity and subsequent clinical pregnancy. However, less is known about the efficiency between each other and whether the combination could further enhance their clinical value. Study design, size, duration Between November 2019 and September 2020, 143 women with a history of at least two or more consecutive implantation failure in IVF/ICSI treatment in Chengdu Xinan Gynecology Hospital were included. They were divided into three groups: ‘ERA + Immune Profiling’ (n = 70), ‘Immune Profiling’ (n = 41), and ‘ERA’ (n = 32). Participants/materials, setting, methods Inclusion criteria were age ≤ 38, with normal uterus and uterine cavity. All patients were suggested to evaluate endometrial receptivity by ERA test (Igenomix, Valencia, Spain) and endometrial immune profiling based on immunohistochemistry simultaneously, who would be free to choose each or both evaluation approaches. Personal Embryo Transfer and/or personal medical care were adopted according to evaluation results. Clinical pregnancy was confirmed by gestational sacs observed under ultrasonography. Main results and the role of chance The overall prevalence of displaced window of implantation (WOI) is 84.3%, and nearly 74.8% (83/111) patients were diagnosed as endometrial immune dysregulation. Clinical Pregnancy rate and embryonic implantation rate decreased in the ‘Immune Test’ groups, but without a statistical difference (P = 0.311, and 0.158, respectively). Multivariable logistic regression analysis showed that different endometrial receptivity evaluation and treatment was not associated the clinical pregnancy rate, suggesting the performance of different endometrial receptivity evaluation and treatment is similar in improving the clinical pregnancy rate. Neither the immune profiling (CD56, P = 0.591; FOXP3, P = 0.195; CD68, P = 0.820; CD163, P = 0.926; CD1a, P = 0.561; CD57, P = 0.221; CD8, P = 0.427; CD138 CE, P = 0.372) nor histologic endometrial dating defined by Noyes criteria (P = 0.374) were associated with ERA phases. Limitations, reasons for caution Although the selection of evaluation approaches was based on patients’ willingness, the variances of baseline characteristics and immune profiling existed in different groups. The immunological treatment efficacy based on immune profiling was not evaluated before embryo transfer. Wider implications of the findings: To our knowledge, this is the first study comparing the pregnancy outcomes after two typical endometrial receptivity evaluation approaches. The findings highlight the unsubstitutability for each assessment, indicating that both asynchronous and pathological WOI contribute to implantation failure. Trial registration number X2019004

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The effect of low-dose aspirin on the pregnancy rate in frozen-thawed embryo transfer cycles: A randomized clinical trial

International Journal of Reproductive BioMedicine ◽

10.18502/ijrm.v13i9.7664 ◽

2020 ◽

Author(s):

Robab Davar ◽

Soheila Pourmasumi ◽

Banafsheh Mohammadi ◽

Maryam Mortazavi Lahijani

Keyword(s):

Clinical Trial ◽

Pregnancy Rate ◽

Embryo Transfer ◽

Low Dose ◽

Endometrial Thickness ◽

Pregnancy Rates ◽

Clinical Pregnancy ◽

Dose Aspirin ◽

Low Dose Aspirin ◽

Clinical Pregnancy Rates

Background: The results of previous studies on the effect of low-dose aspirin in frozenthawed embryo transfer (FET) cycles are limited and controversial. Objective: To evaluate the effect of low-dose aspirin on the clinical pregnancy in the FET cycles. Materials and Methods: This study was performed as a randomized clinical trial from May 2018 to February 2019; 128 women who were candidates for the FET were randomly assigned to two groups receiving either 80 mg oral aspirin (n = 64) or no treatment. The primary outcome was clinical pregnancy rate and secondary outcome measures were the implantation rate, miscarriage rate, and endometrial thickness. Results: The endometrial thickness was lower in patients who received aspirin in comparison to the control group. There were statistically significant differences between the two groups (p = 0.018). Chemical and clinical pregnancy rates and abortion rate was similar in the two groups and there was no statistically significant difference. Conclusion: The administration of aspirin in FET cycles had no positive effect on the implantation and the chemical and clinical pregnancy rates, which is in accordance with current Cochrane review that does not recommend aspirin administration as a routine in assisted reproductive technology cycles. Key words: Aspirin, Embryo transfer, Pregnancy rates.

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O-232 Higher clinical pregnancy rate after oxytocin-receptor antagonist administration around the time of embryo transfer: A systematic review and meta-analysis of eleven RCTs

Human Reproduction ◽

10.1093/humrep/deab128.056 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

K Neumann ◽

G Griesinger

Keyword(s):

Relative Risk ◽

Receptor Antagonist ◽

Pregnancy Rate ◽

Embryo Transfer ◽

Live Birth ◽

Meta Analysis ◽

Oxytocin Receptor ◽

Clinical Pregnancy ◽

Clinical Pregnancy Rate ◽

Receptor Antagonists

Abstract Study question Does the administration of an oxytocin-receptor antagonist around time of embryo transfer in IVF impact the likelihood to achieve a clinical pregnancy? Summary answer Administration of oxytocin-receptor antagonists around embryo transfer increases the likelihood of clinical pregnancy achievement. What is known already Uterine contractions occurring around time of embryo transfer have been described as one possible mechanism of failure of implantation of an embryo in the context of in-vitro fertilization (IVF). Hence the utilization of oxytocin-receptor antagonists was evaluated in randomized clinical trials (RCT) as a therapeutic approach. The compound Atosiban was studied by most RCTs (summarized in Huang et al. 2017). Recently further studies have become available which also investigated the novel agents Barusiban and Nolasiban. This systematic review collates the evidence of all drugs functioning as oxytocin-receptor antagonists which have been investigated in RCTs on IVF treatment so far. Study design, size, duration Multiple literature databases were searched for randomized controlled studies comparing the outcome of IVF cycles with administration of an oxytocin-receptor antagonist in the time period before, during or after embryo transfer versus placebo or nil in IVF patients. Meta-analyses were performed using standard procedures in the software program RevMan v.5.4. All analyses were done per randomized patient, wherever feasible. Participants/materials, setting, methods Eleven RCTs were identified and included in the meta-analysis. Seven utilized the agent Atosiban, one Barusiban and three Nolasiban. These drugs were administered either intravenously, subcutaneously or orally. The patient populations were heterogenous (fresh cycle, frozen-thawed cycle, endometriosis, implantation failure or general IVF-population) between trials. Only four studies reported live birth rates whereas all RCTs reported clinical pregnancy rate. Main results and the role of chance Administration of an oxytocin-receptor antagonist around embryo transfer increases the likelihood of live birth (relative risk: 1.1, 95% CI: 0.99-1.22, p = 0.06, I2=31%, four RCTs, n = 2,510). Accordingly, the ongoing pregnancy rate is increased (relative risk: 1.14, 95% CI: 1.03-1.26, p = 0.01, I2=18%, four RCTs, n = 2,510) as well as the clinical pregnancy rate (relative risk: 1.31, 95% CI: 1.13-1.51, p = 0.0002, I2=61%, eleven RCTs, n = 3,611) by administration of an oxytocin-receptor antagonist. The risk to suffer a miscarriage, however, is not influenced by an oxytocin-receptor antagonist administration (relative risk: 0.90, 95% CI: 0.72-1.12, p = 0.35, I2=0%, seven RCTs, n = 2,936). The risk of multiple pregnancy is not different between groups (relative risk: 1.05 95% CI: 0.81-1.36, p = 0.73, I2=5%, seven RCTs, n = 3,014) as is the risk for an ectopic pregnancy (relative risk: 0.88 95% CI: 0.43-1.8, p = 0.73, I2=0%, four RCTs, n = 2,714). Limitations, reasons for caution Methodological rigor is heterogenous between trials and some of the evidence is of poor quality. Evaluation of included studies is still ongoing and queries are pending. Additionally, there is heterogeneity between patient populations and definition of outcomes; only four RCTs report ongoing pregnancies and live births. Wider implications of the findings The administration of oxytocin-receptor antagonists around embryo transfer increases the pregnancy rate and may be a promising approach to enhance the likelihood to achieve a live birth per embryo transfer. Trial registration number n.a.

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