Assisted reproductive techniques (ART) have
contributed tremendously to the infertility treatment.
As experience has accumulated in the past
three decades, success rates have increased, making
them applied worldwide (
In order to reduce uterine cramps, it is highly recommended to perform embryo transfer with the least trauma. In a study by Fanchin, they showed an increase in random fundocervical uterine contractions in cases of difficult embryo transfer (
Uterine contractions are induced by prostaglandin (PG) which is synthesized from arachidonic acid by cyclo-oxygenase (COX). It seems that pretreatement with uterine relaxants can be helpful in preventing unpleasant cramps. Theoretically non-steroidal anti-inflamatory drugs (NSAIDs) which block the action of COX can inhibit the production of PG and should have beneficial effect on pregnancy rates (
Piroxicam is another NSAID which has been used before embryo transfer in various studies with different results. Its mechanism of action, although being similar to other NSAIDS, is not completely understood, but may be related to prevention of prostaglandin synthesis by a reversible inhibition of the cyclo-oxygenase enzyme (
Due to the controversies in different surveys, this study was performed to assess the effects of administrating Piroxicam prior to embryo transfer in ART.
This pilot study was performed in Vali-e-Asr Hospital from August 2010 through December 2011 after obtaining approval from the Ethical Committee of Tehran University of Medical Sciences in 230 patients who attended the infertility clinic. Inclusion criteria consisted of patients with the age group of 20-35 years old and with ART indication due to tubal factors, ovulation disorders or severe male factor. A long gonadotropin-releasing hormone (GnRH) analogue protocol for pituitary desensitization and recombinant follicle stimulating hormone (rFSH; Gonal-F, Merck Serono,Switzerland) were used for controlled ovarian hyperstimulation. Oocyte retrieval was performed 36-38 hours after human chorionic gonadotropin (HCG) administration which was given when at least two 18 mm follicles were detected. After microinjection, embryo formation and getting a written informed consent, fifty cases who had a good response (> 4 oocytes) during the controlled ovarian hyperstimulation (COH) for ART and who had embryos for transfer, were randomly divided into two groups. Group A received Piroxicam (10 mg, Tolid Daru, Iran) orally half an hour before embryo transfer and group B did not use any form of medication which is the conventional method used (control group). Embryo transfer was done using the Wallace catheter without sonographic control. The patients were asked about their feeling of lower abdominal pain which was considered as having or lacking cramps. Both groups rested for 30 minutes after embryo transfer. Systemic diseases and endometriosis were exclusion criteria. Demographic data, infertility history, endometrial thickness, number of oocytes and embryos transferred, presence of cramps after embryo transfer and ART outcome were recorded in a questionnaire and registered by SPSS version 16. Success rates were compared using chi-square and analysis of variance (ANOVA).
The demographic characteristics and infertility history in both groups showed no significant difference (
After embryo transfer, uterine muscle cramps were reported by 4 women (16%) in group B and none in group A (p=0.03). Seventeen pregnancies (34%) occurred in the 50 patients included in the trial with a pregnancy rate of 32% (n=8) and 36% (n=9) in groups A and B, respectively (
Demographic characteristics of the two groups under study
|Group Characteristics||Control(Group B) N=25||Piroxicam(Group A) N=25||Total N= 50||P value|
|27.68 ± 4.58||28.649 ± 4.32||28.16 ± 4.45||NS**|
|32.86 ± 4.02||34.09 ± 4.09||33.48 ± 4.05||NS**|
|6.18 ± 3.37||6.70 ± 3.94||6.44 ± 3.63||NS**|
NS; Non-significant,*; Chi-square test and **; ANOVA.
Comparison of outcomes of the two groups under study
|Group Outcome||Piroxicam||Control||P value|
NS; Nonsignificant and *; Chi-square test.
In ART cycles, different factors contribute to the success rates. Technical aspects of embryo transfer is one of the most important factors, besides the high quality embryos and uterine receptivity. Even with an atraumatic transfer, endometrial reaction can be induced and affect ART (
In recent years, attention has been paid to reduce or prevent uterine contractions or cramps using prostaglandin inhibitors or sedatives before transfer. Indomethacin and piroxicam are the two mostly cited prostaglandin inhibitors used before embryo transfer (
In different studies, Piroxicam is considered as a controversial topic. Moon et al. (
In rodents and rabbits, implantation can be interrupted by injection of prostaglandin inhibitors (
Since prostaglandins play a key role in implantation, due to the present evidence, it seems reasonable to omit NSAIDs administration as a means of reducing uterine contractions in embryo transfer procedure until further evidence can prove their benefits. In spite of our findings, since this study was performed on a limited number of patients and since other numerous factors are involved in this process, we recommend that more precise studies be performed on a wider scale in order to obtain more accurate results.
It seems that piroxicam administration 30 minutes prior to embryo transfer can not significantly increase pregnancy rates, but can prevent or reduce uterine cramps after the procedure.