I Missed a Dose of My Baby Aspirin Pregnant Post Fet

Int J Reprod Biomed. 2020 Sep; 18(nine): 693–700.

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

Robab Davar

¹Research and Clinical Middle for Infertility, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.

Soheila Pourmasumi

^twoNon-Communicable Diseases Inquiry Center, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.

ⁱⁱⁱClinical Research Development Unit (CRDU), Moradi Hospital, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.

Banafsheh Mohammadi

ⁱInquiry and Clinical Heart for Infertility, Yazd Reproductive Sciences Establish, Shahid Sadoughi Academy of Medical Sciences, Yazd, Iran.

Maryam Mortazavi Lahijani

¹Research and Clinical Middle for Infertility, Yazd Reproductive Sciences Constitute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.

⁴Department of Obstetrics and Gynecology, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.

Received 2019 December xvi; Revised 2020 Feb 1; Accepted 2020 February 23.

Abstract

Background

The results of previous studies on the upshot of depression-dose aspirin in frozen-thawed embryo transfer (FET) cycles are limited and controversial.

Objective

To evaluate the event 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 chief issue was clinical pregnancy rate and secondary event measures were the implantation charge per unit, 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 meaning differences between the ii groups (p = 0.018). Chemical and clinical pregnancy rates and ballgame rate was similar in the 2 groups and there was no statistically significant difference.

Decision

The assistants 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 every bit a routine in assisted reproductive engineering science cycles.

Keywords: Aspirin, Embryo transfer, Pregnancy rates.

1. Introduction

Human reproduction depends on a successful implantation and the evolution of an embryo on the endometrial surface. A receptive endometrium is a main cistron for embryo implantation. Adjuvant therapy has been utilized to better the thickness and vascularity of the endometrium with the purpose of improving implantation rates. One of this adjuvant therapies is low-dose aspirin assistants (1).

There have been several studies on the result of low-dose aspirin in assisted reproductive technology (ART) cycles, just contradictory and limited results accept been reported on the upshot of aspirin on the endometrial thickness besides as on the frozen-thaw embryo transfer (FET) cycles (ii, three).

Several studies showed that there was a direct correlation between an increased uterine vascular resistance and decreased endometrial and sub-endometrial blood menstruation with poor implantation and pregnancy charge per unit (4-6). Aspirin can inhibit platelet assemblage and increases blood flow past changing the balance between thromboxane (which is a vasoconstrictor mediator) and prostaglandin (which is vasodilator mediator) (1). Every bit per the recent studies, low-dose aspirin appears to be safe and well-tolerated by pregnant women (vii, 8). Other aspirin machinery is increasing it in the level of integrin B3 and Leukemia inhibitory gene (LIF) expression in the endometrium (ix).

In a meta-analysis Wang and colleagues suggested that "low-dose aspirin may increase the pregnancy rate in In vitro fertilization/intra cytoplasmic sperm injection (IVF/ICSI) and recommended 100 mg/twenty-four hours ASA clinical use. Considering of the limitation of the included studies, more well-designed large-scaled RCTs (randomized clinical trial) are necessary to confirm the result of aspirin on the endometrial thickness in the FET cycles" (10).

Madani and colleagues performed a pilot clinical trial, where sixty patients who were candidates for FET bike were divided into 2 groups. Group A received 100 mg aspirin orally and the other group received placebo. Finally, they reported that the administration of aspirin in FET cycles improved implantation rate, clinical pregnancy rate, and live birth rate. They also recommended that a large sample size is likewise necessary to ostend the effect of aspirin on the FET cycles (11). Fatemi and colleagues, on the other hand in a review study reported contradictory results about the upshot of aspirin on the IVF cycles (12). Haapsamo and colleagues, reported that the assistants of aspirin in ovarian stimulation cycles improved uterine hemodynamic status compared to the control grouping (13). In another written report, the authors showed that the assistants of aspirin in patients undergoing IVF cycle reduced uterine artery pulsatility alphabetize (PI) in the early and mid-pregnancy and reduced the risk of preeclampsia and intrauterine growth restriction (IUGR) (14).

In a systematic review, researchers concluded that there is insufficient show for routine administration of aspirin in IVF cycles. On the other mitt, they reported that the administration of aspirin has no positive pregnant effects on IVF result and needs further studies (xv). Dirckx and co-worker in Kingdom of belgium establish no positive effect of aspirin in improving clinical pregnancy in IVF cycles and recommended that it should not be used routinely (3). Also, in a recent Cochrane review, the authors concluded that the utilise of empirical aspirin for general IVF population cannot be recommended for routine employ (16).

Based on the contradictory results and the lack of sufficient studies on the effect of aspirin on the pregnancy rate in FET, in our written report nosotros aimed to investigate the issue of low-dose aspirin adjuvant therapy in women undergoing FET cycles.

2. Materials and Methods

This written report was a randomized clinical trial performed in the Research and Clinical Center for Infertility, Yazd Reproductive Sciences Institute from January 2019 to February 2020.

The inclusion criteria were age $<$ 40 yr, at to the lowest degree ii frozen-thawed embryos available for another transfer, no contraindications for aspirin assistants, no uterine disorders, no endometriosis, no history of uterine surgery, and no history of recurrent abortion (two or more than than two abortions).

128 eligible women who were assigned for FET participated in the study. They were allocated into ii groups randomly and as. Grouping A (n = 64) was prescribed lxxx mg aspirin, and for group B (northward = 64), no treatment was prescribed to the routine FET protocols (Tabular array I).

First, all patients underwent transvaginal ultrasonography on the second day of their cycles for excluding functional ovarian cysts. For endometrial preparation, patients received 6 mg estradiol valerate (aburahan co.) per day from 2d solar day of their cycles, and if the endometrial thickness was 7 mm or less on the thirteenth day of their cycles, the dose was increased to 10 mg.

When the optimal endometrial thickness ( $>$ eight mm) was obtained, vaginal progesterone 400 mg BID was started and continued until the 12 week of pregnancy. For endometrial thickness measurement, transvaginal ultrasonography (fillips analogousness 70) was performed from the xiii $^{th}$ 24-hour interval of their cycles and every 4 days if the endometrial thickness of 8 mm was non obtained on the 13th mean solar day.

The two selected embryos were transferred at cleavage stage by Cook catheter. 5000 IU HCG (human chorionic gonadotropin) was administered on the outset, third, and 6th days of embryo transfer.

In our written report twenty days afterward the embryo transfer beta man chorionic gonadotropin (βHCG) was checked. The master outcome was clinical pregnancy rate that determined as presence of an intrauterine gestational sac with fetal center crush (28-42 days afterwards the embryo transfer). We requested women to continue taking aspirin for until 12 weeks of gestation. Secondary outcomes were implantation and miscarriage rates. The implantation rate was determined as the total number of gestational sacs per total number of transferred embryos, and the miscarriage rate was determined every bit the number of miscarriage that took place until the 20 $^{th}$ week of pregnancy.

Table 1

Basic patient characteristics and clinical parameters in ii study groups


Variables		ASA group (n = 63)	Control group (n = 62)	P-value
Historic period (Year)*		29.48 $\pm$ 4.78	29.65 $\pm$ 4.52	0.835
BMI (kg/m $^{ii}$ )*
	$\leq$ 24.9	xx (31.25)	16 (25.00)	0.106
	25-29.9	30 (46.88)	38 (59.37)
	$\geq$ 30	14 (21.87)	ten (15.62)
Duration of infertility (Yr)*		7.09 $\pm$ 3.49	7.37 $\pm$ 3.lxx	0.659
Number of previous embryo transfer cycles **
	1	39 (60.nine)	35 (54.7)	0.369
	2	23 (35.9)	25 (39.1)
	3	2 (iii.1)	iv (half dozen.2)
Bike cancellation rate **		1 (1.6%)	2 (iii.1)	i.00
Endometrial thickness (mm)*		viii.64 $\pm$ 1.sixty	9.29 $\pm$ 1.70	0.028*
Data presented as Hateful $\pm$ SD (Educatee t test) * Data presented as north (%) (chi-square test)

Ethical consideration

The study has been approved by the upstanding committee of the Yazd Reproductive Sciences Establish (IR.SSU.RSI.REC.1398.003). All participants gave informed consent being included in the study.

Statistical analysis

Information were analyzed using the Statistical Bundle for the Social Sciences fifteen.0 software. The baseline characteristics of the 2 groups of patients were compared using the educatee t test. Differences in the pregnancy outcomes of the two groups were analyzed using the Chi-square examination. P $\leq$ 0.05 was considered statistically significant.

3. Results

In the present written report, from 700 women who candidate for FET 572 were excluded from our study and nosotros evaluated a total of 128 patients in 2 study groups: 64 cases in ASA (amino salicylic acid) group and 64 in control group. There was one cancelled cycle in case grouping (ane/64) and 2 in command group (2/64) due to sparse endometrium ( $<$ 7 mm) (Figure i). As shown in table I, the historic period, BMI, infertility duration, and the number of previous embryo transfer cycles had similarity in the two study groups, and at that place was no statistically meaning difference between the two groups. The endometrial thickness was lower in the group receiving ASA in comparing to the control group. The difference was statistically significant betwixt the two groups (p = 0.028; Table I). Fine art outcomes in the ii study groups are summarized in table Ii. The quality of transferred embryo was similar in the 2 groups and the highest number of embryos were in expert quality (A and B). In all cycles, we transferred ii embryo. From 126 transferred embryo in case group, 16 pregnancy sacs were observed in ultrasonography, and from 124 transferred embryo in control group, 18 pregnancy sacs were observed in ultrasonography. The Implantation rate was higher in the control group (fourteen.five% vs. 12.6%), but this difference was not statistically pregnant. Chemical and clinical pregnancy rates were similar in the ii groups, and there was no statistically meaning difference.

Table two

Art outcome in two study groups


Variables		ASA group (n = 63)	Control group (northward = 62)	P-value
Embryo quality*
	A	8 (12.seven)	15 (24.two)	0.251
	B	38 (60.3)	32 (51.6)
	C	17 (27.0)	15 (24.2)
Implantation rate*		16/126 (12.69)	xviii/124 (14.51)	0.759
Chemic pregnancy charge per unit*		nineteen (30.2)	xv (24.2)	0.547
Clinical pregnancy rate*		15 (23.8)	12 (19.four)	0.665
Abortion/clinical pregnancy**		0/fifteen	0/12
* Information presented as due north (%). chi-foursquare examination ** data presented as n (%) Note: Information obtained past descriptive statistics; data presented number (%); P $\leq$ 0.05 considered statistically pregnant

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4. Discussion

The results of our study showed that there was no difference in the pregnancy outcome and the clinical pregnancy charge per unit in patients who received aspirin in comparison with the control group in patients undergoing FET cycles. The endometrial thickness was significantly lower in the aspirin group than the control group. Some studies have investigated the role of aspirin in ART cycles and reported contradictory results (17, xviii).

The majority of previous studies investigated the role of aspirin as an adjuvant therapy on ART event in fresh cycles (stimulated cycles) (17, xix). In fresh cycles, the estradiol levels are higher than in the freeze-thaw cycles. Too, in a fresh cycle, embryo is exposed to supra-physiological levels of estrogen during implantation only in the frozen-thaw cycles endometrial preparation is done artificially by estrogen and progesterone assistants and the embryo is non exposed to supra-physiological level of estrogen. Supra-physiologic levels of estrogen may have a negative bear on on endometrial receptivity and maybe responsible for implantation failure in Fine art (xx, 21). Therefore, the results of aspirin adjuvant therapy in the fresh and frozen cycles are noncomparable. The results of the past studies on the effect of low-dose aspirin in FET cycles are limited.

The effect of ART event in the present written report was in dissimilarity with Madani'south study. They reported that the administration of aspirin in FET cycles improved the implantation, clinical pregnancy, and live birthrates, notwithstanding, nosotros found no statistically pregnant improvement in the biochemical, clinical pregnancy, and ballgame rates in the aspirin group in comparison with the control. However, their study was a airplane pilot study and the difference between the results of our study and the Madani's study may be the depression sample size of their study (xi).

Hsieh and colleagues showed higher clinical pregnancy rate and better endometrial pattern in patients with thin endometrium afterwards aspirin assistants, and because in this group they selected patients who had thin endometrium their results is in contrast to our findings (22).

Befitting to our report, a meta-assay (15) and reports past Cochrane reviews (16, 23) also establish that there was no improvement in pregnancy rates with the use of low-dose aspirin. Jeromeh demonstrated that the clinical pregnancy rate was lower in the aspirin grouping compared with command grouping (eleven.1% vs 33.3% respectively) for, and the implantation rates were two.9 and x.9%, respectively. In this study, low-dose aspirin assistants did not crusade positive upshot on pregnancy rates in FET cycles (24). Gelbaya and co-workers suggested that in FET cycles, there was no significant difference in pregnancy rate between untreated women with normal uterine perfusion and those that uterine perfusion was improved later on aspirin assistants. This result is like with our written report (25). In another report, Doppler ultrasound was used for uterine perfusion assessment and patients were classified as ii groups: normal uterine perfusion and impaired uterine perfusion. administration of low-dose aspirin to hormone replacement therapy in women with dumb uterine perfusion was associated with improved uterine perfusion and acceptable pregnancy rates but without whatsoever benefits in patients with normal perfusion (26). In our study, the cess of uterine perfusion and patients nomenclature was non done.

v. Determination

Our study concludes that the administration of aspirin in frozen-thaw cycles had no positive effect on the implantation, chemical, and clinical pregnancy rates, and is in accordance with the current Cochrane review that does non recommend aspirin assistants as a routine in Art cycles.

Disharmonize of Interest

The authors have no financial or nonfinancial conflicts of interest.

Acknowledgments

The authors would like to thank the staff from the Research and Clinical Centre for Infertility, Shahid Sadoughi University of Medical Sciences, Yazd, Iran, for their skillful technical assistance during the class of this written report. The study was financially supported by the Research Deputy of the Shahid Sadoughi Academy of Medical Sciences, Yazd, Iran.

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Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7521165/