A Randomised Controlled Trial to Study the Efficacy of Administration of Atosiban Before Embryo Transfer on In Vitro Fertilisation

Aashna Arora; Kanad Dev Nayar; Sabina Sanan; Manika Sachdeva; Gaurav Kant; Ananya Singh; Meetakshara Singh

doi:10.25259/FSR_38_2025

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Original Article

2025

:12;

doi:

10.25259/FSR_38_2025

A Randomised Controlled Trial to Study the Efficacy of Administration of Atosiban Before Embryo Transfer on In Vitro Fertilisation

Aashna Arora^1,, Kanad Dev Nayar¹, Sabina Sanan¹, Manika Sachdeva¹, Gaurav Kant¹, Ananya Singh¹, Meetakshara Singh¹

1Department of Reproductive Medicine, Akanksha IVF Centre, Mata Chanan Devi Hospital, New Delhi, India.

*Corresponding author: Aashna Arora, Department of Reproductive Medicine, Akanksha IVF Centre, Mata Chanan Devi Hospital, New Delhi, India. aashnalhmc@gmail.com

Received: 2025-06-26, Accepted: 2025-11-05, Published: 2025-12-31

Licence

This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-Share Alike 4.0 License, which allows others to remix, transform, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.

How to cite this article: Arora A, Nayar KD, Sanan S, Sachdeva M, Kant G, Singh A, Singh M. A Randomised Controlled Trial to Study the Efficacy of Administration of Atosiban Before Embryo Transfer on In Vitro Fertilisation. Fertil Sci Res. 2025;12:39. doi: 10.25259/FSR_38_2025

Abstract

Objectives:

This randomised controlled trial aimed to assess the efficacy of Atosiban in women undergoing frozen embryo transfer. The specific objectives were to assess the clinical pregnancy rate (PR), implantation rate (IR), biochemical PR and first-trimester miscarriage rate.

Material and Methods:

The study was conducted at Akanksha in vitro fertilisation (IVF) Centre, New Delhi, from 28 December 2024 to 28 May 2025. A total of 100 women aged 23–40 years undergoing an frozen embryo transfer (FET) cycle were included in the study. Other inclusion criteria are body mass index (BMI) < 30 kg/m², normal uterus on 2D ultrasonography, endometrial thickness ≥ 7 mm on the day of starting progesterone, and at least two good-quality embryos - blastocyst (4AA, 4AB, 4BA, 3AA) transferred. Uterine factors like Ashermann’s syndrome, space-occupying lesions like adenomyosis, fibroids and recurrent implantation failure were excluded from the study. Patients who underwent FET cycles were categorised into two groups: Group A (50 patients)— patients who underwent FET after administration of Atosiban; Group B (50 patients)—patients who underwent FET without prior administration of Atosiban, hence acting as controls. The randomisation of patients was done by a computer-based programme into two groups. A baseline scan was done on Day 2/Day 3. Endometrial preparation was done by sequential incremental administration of oral oestradiol until endometrial thickness was ≥7 mm, followed by oestradiol combined with injectable progesterone as luteal phase support, P + 5 days, where P stands for progesterone (P + 5 refers to 5 days of administration of progesterone). Atosiban IV bolus of 6.75 mg was administered 30 minutes before embryo transfer. Frozen embryo transfer was done in both groups, in which two good-quality blastocysts (4AA, 4AB, 4BA, 3AA) were transferred. A urine pregnancy test or serum beta-human chorionic gonadotrophin (HCG) levels were done 14 days after FET. In case of a positive pregnancy test, the patient was followed up at 6–7 weeks of gestation to assess the pregnancy outcome. In case of a viable pregnancy, the patient was followed up at 11–12 weeks of gestation.

Results:

Baseline characteristics of both the study groups—age, duration of infertility, S.Antimullerian hormone (AMH), antral follice count (AFC), S.Estradiol—were similar. Group A patients in whom Atosiban was given prior to embryo transfer demonstrated a statistically significantly higher clinical PR as compared to Group B patients without Atosiban (58 vs. 38, p < 0.05). Group A patients demonstrated a higher IR as compared to Group B (33.33 vs. 23.80, p < 0.12), and the biochemical PR was also higher in Group A patients as compared to Group B patients without Atosiban (20 vs. 14, p < 0.42), but the differences were not statistically significant. The first-trimester miscarriage rate was lower in Group A with Atosiban as compared to Group B without Atosiban (17.24 vs. 21.05, p < 1); however, the difference was statistically not significant.

Conclusion:

The administration of Atosiban before embryo transfer in women has led to an increase in the clinical PR, thus increasing the success rate of the assisted reproductive technology (ART) cycle.

Keywords

Atosiban

Clinical pregnancy rate

Embryo transfer

Implantation rate

Miscarriage rate

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INTRODUCTION

Embryo implantation is the most crucial stage in assisted reproduction treatment. It is affected by several factors, including the age of the patient, embryo quality and endometrial receptivity. ^[1–4]

Uterine contractions triggered by the embryo transfer process might negatively impact embryo implantation.^[5] Elevated serum oestradiol levels following an ovarian stimulation cycle may lead to endometrial production of oxytocin, increase the expression of oxytocin receptors and indirectly stimulate the synthesis and release of prostaglandin F2α.^[6–9]

Approximately 30% of patients undergoing embryo transfer experience excessive uterine contractions (more than 5 per minute), which are significantly linked to poorer in vitro fertilisation (IVF) outcomes. ^[10,11]

Atosiban is an oxytocin receptor antagonist and is primarily used to delay imminent preterm labour.^[12] The impact of Atosiban on embryo implantation is related to the inverse correlation between the frequency of uterine contractions and the implantation rate (IR).^[13] Additionally, the vasopressin 1a antagonist function of Atosiban may provide benefits by enhancing endometrial and uterine muscle perfusion through the relaxation of the uterine arteries.^[14] V1a vasopressin receptors are also involved in mediating platelet aggregation.^[15]

Certain measures can be adopted to minimise uterine contractions on the day of embryo transfer, such as being very gentle in manipulating embryos during IVF, using soft catheters during the process and starting progesterone administration on the day of oocyte retrieval.^[6,16] The use of Atosiban before embryo transfer is one such method we have studied.

We conducted a randomised controlled trial to study the efficacy of administration of Atosiban before embryo transfer in in vitro fertilisation.

MATERIAL AND METHODS

Study Design

This randomised controlled trial included 100 women undergoing the frozen embryo transfer (FET) cycle at Akanksha IVF Centre from 28 December 2024 to 28 May 2025, fulfilling the inclusion and exclusion criteria.

Inclusion Criteria

Patients diagnosed with either primary or secondary infertility, aged 23–40 years, having a BMI (body mass index) of <30 kg/m² with a normal uterus on two-dimensional (2D) ultrasonography, endometrial thickness ≥ 7 mm on the day of starting progesterone and undergoing FET where at least two good-quality blastocysts (4AA, 4AB, 4BA, 3AA) were transferred.

Exclusion Criteria

Patients with a history of recurrent implantation failure, having any uterine defects like Asherman’s syndrome or any space-occupying lesions in the uterus like fibroids or adenomyosis, were excluded from the study.

METHODOLOGY

Patients undergoing FET cycles were categorised into two groups: Group A (50 patients)—patients undergoing FET planned for administration of Atosiban prior to embryo transfer; Group B (50 patients)—patients undergoing FET without prior administration of Atosiban, hence acting as controls. The randomisation of patients was done by a computer-based programme into two groups. A baseline scan was done on Day 2/Day 3. Endometrial preparation was done by sequential incremental administration of oral oestradiol, starting with an average dose of 6 mg/day, increased to 12 mg/day, until endometrial thickness is ≥7 mm, followed by oestradiol combined with injectable progesterone as luteal phase support, P + 5 days. An Atosiban IV bolus of 6.75 mg was administered 30 minutes before embryo transfer. Frozen embryo transfer was done in both groups, in which two good-quality blastocysts (4AA, 4AB, 4BA, 3AA) were transferred. A urine pregnancy test or serum beta-human chorionic gonadotrophin (HCG) levels were done 14 days after FET. In case of a positive pregnancy test, the patient was followed up at 6–7 weeks of gestation to assess the pregnancy outcome. In case of a viable pregnancy, the patient was followed up at 11–12 weeks of gestation.

Primary Outcome

Clinical pregnancy rate (PR)

Secondary Outcome

IR
Biochemical PR
Clinical miscarriage rate

Definitions and Criteria Used

Clinical pregnancy was defined as the presence of an intrauterine gestational sac accompanied by cardiac activity.
$Clinical pregnancy rate = \frac{Number of clinical pregnancies \times 100}{Number of embryo transfer cycles}$
IR was defined as the percentage of embryos that successfully implanted in the uterine lining.
$Implantation rate = \frac{Number of gestational sacs \times 100}{Number of transferred embryos}$
Biochemical pregnancy was defined by falling serum beta-HCG titres with non-visualisation of the intrauterine gestational sac on transvaginal ultrasound.
$Boichemical pregnancy rate = \frac{Number of biochemical pregnancies \times 100}{Number of embryo transfer cycles}$
Clinical miscarriages include loss of pregnancy up to 12 weeks of gestation.
$Clinical miscarriage rate = \frac{Number of Clinical miscarriages \times 100}{Number of embryo transfer cycles}$

Statistical Analysis

The collected data were entered in Microsoft Excel and then analysed and statistically evaluated using SPSS 25 version. The normality of each variable was assessed by using the Kolmogorov-Smirnov test. Quantitative data were expressed by mean and standard deviation, and the difference between the means of two groups was tested by the unpaired t-test or Mann-Whitney U-test. Qualitative data were expressed in percentages, and the differences between the percentages of two groups were tested by the chi-square test or Fisher’s exact test. p < 0.05 was considered statistically significant.

RESULTS

Baseline characteristics of both the study groups—age, duration of infertility, serum antimullerian hormone (AMH), antral follice count (AFC) and serum estradiol were similar in study and control groups [Table 1; Figure 1]. Group A patients in whom Atosiban was given prior to embryo transfer demonstrated a statistically significantly higher clinical PR as compared to Group B patients without Atosiban (58 vs. 38, p < 0.05). Group A patients demonstrated a higher IR as compared to Group B (33.33 vs. 23.80, p < 0.12), and the biochemical PR was also higher in Group A patients as compared to Group B patients without Atosiban (20 vs. 14, p < 0.42), but the differences were not statistically significant. The first-trimester miscarriage rate was lower in Group A with Atosiban as compared to Group B without Atosiban (17.24 vs. 21.05, p < 1); however, the difference was statistically not significant [Table 2; Figure 2].

Table 1: Comparison of baseline characteristics of the two groups.

Baseline data	Group A (cases), n = 50 Mean (SD)	Group B (controls), n = 50 Mean (SD)	P-value
Mean age (in years)	34.72 ± 4.45	36.48 ± 5.72	0.08
Husband’s age (in years)	37.10 ± 3.88	39.08 ± 5.51	0.06
BMI	22.93 ± 1.15	22.2 ± 1.68	0.07
Duration of infertility	5.84 ± 4.72	6.89 ±5.43	0.24
Types of infertility
Primary infertility	20 (40%)	26 (52%)	0.22
Secondary infertility	30 (60%)	24 (48%)	0.22
S. AMH	2.38 ± 2.63	3.52 ± 4.57	0.08
AFC	7.16 ± 4.53	6.88 ± 4.14	0.81
E2	2119.04 ± 1362.13	2782.22 ± 1197.60	0.01
Embryos transferred	1.80 ± 0.40	1.68 ± 0.47	0.17

SD: Standard deviation, BMI: Body mass index, AMH: Anti-mullerian hormone, AFC: Antral follicle count, E2: Estradiol. P-value significance threshold: P< 0.05.

Comparison of baseline characteristics of the two groups.

Table 2: Outcome of IVF- embryo transfers in the control and atosiban treatment groups.

Clinical outcome (%)	Group A (cases), n = 50	Group B (controls), n = 50	P-value
Clinical pregnancy rate	29/50 (58)	19/50 (38)	0.04
Implantation rate	30/90 (33.33)	20/84 (23.80)	0.12
Biochemical pregnancy rate	10/50 (20)	7/50 (14)	0.42
Clinical miscarriage rate	5/29 (17.24)	4/19 (21.05)	1

P-value significance threshold: P< 0.05.

Outcome of In Vitro Fertilization-embryo transfers in the control and atosiban treatment groups.

DISCUSSION

Embryo transfer is the most crucial step in assisted reproduction treatment. Atosiban was associated with an increase in the rate of clinical pregnancy.

A similar randomised controlled trial was conducted by Hebisha et al. in 2016^[1] in which they had recruited 182 women, using long agonist protocol and randomly divided them into two groups: Group A (n = 91), who received 7.5 mg Atosiban by slow IV injection and Group B (n = 91), who received a placebo as a 0.9% sodium chloride solution, also by IV injection, 20 minutes before embryo transfer (blastocyst stage ET), and similar results were found. The PR was higher in Group A with Atosiban (58/91) as compared to Group B without Atosiban (44/91) (63.7% vs. 48.4%), p = 0.037. Also, the IR was higher in Group A with Atosiban compared to Group B without Atosiban (45.20% vs. 34.69%), respectively; p = 0.045.^[1]

A study was conducted in Srinagarind Hospital, a university hospital in Khon Kaen, Thailand, by Buddhabunyakan et al. in 2021.^[17] They performed a randomised controlled trial in which they had included 25 patients in the placebo group and 25 patients in the Atosiban group. Women in the study group received intravenous Atosiban 6.75 mg 30 minutes before embryo transfer and continued infusion at 18 mg/hour for 1 hour. The dose was reduced to 6 mg/hour for another 2 hours. Saline solution was applied in the placebo group. The IR and the clinical PR were not statistically significantly different between the Atosiban group and the placebo group (37.5% vs. 31.0% and 44% vs. 36%).^[17]

A Cochrane analysis was done in 2021 by Craciunas et al., in which they reviewed seven randomised controlled trial (RCTs).^[18] From their study, they had concluded that it was uncertain whether intravenous Atosiban improves pregnancy outcomes for women undergoing assisted reproductive technology (ART). The evidence was of very low to high certainty.^[18]

Ozlem Moraloglu et al. conducted a prospective, randomised, placebo-controlled clinical study in which 180 women were included, and they were randomly allocated into treatment and control groups.^[19] The treatment group received Atosiban in a dose of 37.5 mg, and placebo medication was given in the control group. The clinical PR per cycle and IR per transfer were 46.7% and 20.4% in the Atosiban-treated group, which were significantly higher than in the control group (28.9% and 12.6%, respectively), p = 0.01. The miscarriage rates of groups 1 and 2 were 16.7% and 24.4%, respectively (p = 0.01). These results have indicated that Atosiban increases the IR and PR after IVF embryo transfer. ^[19]

Kadhim et al.^[20] conducted a study to compare the effect of Atosiban and piroxicam administration on the day of embryo transfer on IR, clinical PR, miscarriage rate and live birth rate. It included 60 infertile patients, and they were randomly divided into two groups. The first group received a bolus dose of Atosiban 6.75 mg intravenously 30 minutes before embryo transfer. In the second group, they gave piroxicam suppositories 20 mg 1–2 hours before embryo transfer. The group with Atosiban showed higher pregnancy, implantation and live birth rates than the piroxicam group (60% vs. 53.3%, 37.8% vs. 23.9% and 94.4% vs. 81.25%, respectively) and a lower miscarriage rate compared to piroxicam (5.6% vs. 18.75%); however, there were no significant differences between the two groups with p > 0.05.^[20,21]

Schwarze et al.^[22] conducted a systematic review and meta-analysis of randomised and non-randomised trials in 2020. They had done a systematic review of papers using MEDLINE and EMBASE (1990–2019). They had included four randomised controlled trials including 1025 women, and two nonrandomised trials including 686 patients. It was found that Atosiban increased clinical PR s regardless of the indication for ART or the type of embryo transferred. ^[22] Strengths: There are only a few studies worldwide that have demonstrated the efficacy of Atosiban given prior to embryo transfer in in vitro fertilisation. This study is one such contribution in this field.

Limitations

It is a single-centre study with a small sample size. The study duration is also short. Patients could not be followed till childbirth due to paucity of time owing to a shorter study period.

CONCLUSION

The administration of Atosiban before embryo transfer in women has led to an increase in the Clinical PR, thus increasing the success rate of the ART cycle.

Author contribution:

KDN, SS, AA: Concept; KDN, AA, MS: Design; SS, AA: Definition of Intellectual content; AA, MS: Literature search; AA, GK: Data acquisition and analysis; KDN, AA, AS: Manuscript preparation; KDN, AA, MS: Manuscript editing and review.

Ethical approval:

The research/study was approved by the Institutional Review Board at Indian Fertility Society, approval number F.1/IEC/IFS/2024/No.27, dated 27th December 2024.

Declaration of patient consent:

The authors certify that they have obtained all appropriate patient consent.

Conflicts of interest:

There are no conflicts of interest.

Use of artificial intelligence (AI)-assisted technology for manuscript preparation:

The authors confirm that there was no use of artificial intelligence (AI)-assisted technology for assisting in the writing or editing of the manuscript, and no images were manipulated using AI.

Financial support and sponsorship: Nil.

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