V Thalluri1, K P Tremellen. 1. Department of Gynaecology, Royal Adelaide Hospital, North Terrace, Adelaide, South Australia 5000, Australia.
Abstract
STUDY QUESTION: Does the presence of ultrasound diagnosed adenomyosis interfere with successful implantation in patients undergoing IVF treatment with GnRH antagonist ovarian stimulation? SUMMARY ANSWER: The presence of ultrasound diagnosed adenomyosis was associated with a significant reduction in successful implantation of good quality embryos in patients undergoing GnRH antagonist stimulation for IVF treatment (viable clinical pregnancy rate 23.6% versus 44.6%, P= 0.017). WHAT IS KNOWN AND WHAT THIS PAPER ADDS: There is currently no consensus regarding the impact of adenomyosis on implantation potential. Although some studies have identified alterations in the endometrial milieu in adenomyosis patients that may impact implantation, several papers have reported no associated reproductive deficit. However, these pregnancy outcome studies have primarily investigated patients undergoing long down-regulation IVF protocols, where low levels of serum estrogen (before commencing the ovarian stimulation) may inactivate the adenomyosis and potentially negate its effect on implantation. Given that the majority of fertility clinics are now moving towards the more 'patient-friendly' antagonist protocol, where patients are not placed in a hypo-estrogen state before commencing ovarian stimulation, the question of whether adenomyosis has an impact on IVF success rates in GnRH antagonist-stimulated IVF treatment needs to be examined. DESIGN: This is a retrospective cohort study of 748 patients who, between April 2010 and March 2012, underwent a screening transvaginal ultrasound to identify possible pelvic pathology before commencing their IVF treatment. From this screening group, 213 patients were eligible to be included in the study as they had no obvious underlying uterine or embryonic factors that could have interfered with successful implantation (aged ≤39 years, good quality Day 4/5 embryo for single-embryo transfer, no uterine fibroids/hydrosalpinx or endometrial polyps). PARTICIPANTS AND SETTING: There were 213 patients in a private IVF unit eligible to be included in the study, with 38 patients (17.84%) having ultrasound diagnosed adenomyosis and 175 patients having no adenomyosis on the scan. Only the first treatment cycle for each patient was included. MAIN RESULTS AND THE ROLE OF CHANCE: The adenomyosis group had a viable clinical pregnancy rate of 23.6% compared with 44.6% in the non-adenomyosis group (P =0.017). However, the median maternal age and duration of infertility of the adenomyosis group was 2 years older and 4 months greater, respectively, than that of the non-adenomyosis group. A logistic regression analysis was performed to account for these differences between the two groups, with the adjusted results still showing a statistically significant decline in viable pregnancy rate in the adenomyosis group (OR = 0.408, CI = 0.181-0.922, P =0.031 when adjusting for maternal age; OR = 0.417, CI = 0.175-0.989, P =0.047 when adjusting for duration of infertility) BIAS, CONFOUNDING AND OTHER REASONS FOR CAUTION: Given the retrospective nature of this study, there is risk of bias. This risk was minimized by having subjective variables such as embryo quality assessed by individuals not involved in the study, while strictly applying the pre-determined inclusion/exclusion criteria to all study participants. Furthermore, it is acknowledged that ultrasound is not a perfect test for the diagnosis of adenomyosis and, therefore, may underestimate the incidence of adenomyosis by misclassifying some patients with mild adenomyosis as not affected. WIDER IMPLICATIONS OF THE FINDINGS: The results of this study should be representative of outcomes for any patient undergoing a GnRH antagonist ovarian stimulation cycle for IVF since standard IVF treatment protocols were used. STUDY FUNDING/COMPETING INTEREST: MSD Australia have provided us with a small amount of funding to cover our costs (including a travel grant for Dr Thalluri to present this work at a conference).
STUDY QUESTION: Does the presence of ultrasound diagnosed adenomyosis interfere with successful implantation in patients undergoing IVF treatment with GnRH antagonist ovarian stimulation? SUMMARY ANSWER: The presence of ultrasound diagnosed adenomyosis was associated with a significant reduction in successful implantation of good quality embryos in patients undergoing GnRH antagonist stimulation for IVF treatment (viable clinical pregnancy rate 23.6% versus 44.6%, P= 0.017). WHAT IS KNOWN AND WHAT THIS PAPER ADDS: There is currently no consensus regarding the impact of adenomyosis on implantation potential. Although some studies have identified alterations in the endometrial milieu in adenomyosispatients that may impact implantation, several papers have reported no associated reproductive deficit. However, these pregnancy outcome studies have primarily investigated patients undergoing long down-regulation IVF protocols, where low levels of serum estrogen (before commencing the ovarian stimulation) may inactivate the adenomyosis and potentially negate its effect on implantation. Given that the majority of fertility clinics are now moving towards the more 'patient-friendly' antagonist protocol, where patients are not placed in a hypo-estrogen state before commencing ovarian stimulation, the question of whether adenomyosis has an impact on IVF success rates in GnRH antagonist-stimulated IVF treatment needs to be examined. DESIGN: This is a retrospective cohort study of 748 patients who, between April 2010 and March 2012, underwent a screening transvaginal ultrasound to identify possible pelvic pathology before commencing their IVF treatment. From this screening group, 213 patients were eligible to be included in the study as they had no obvious underlying uterine or embryonic factors that could have interfered with successful implantation (aged ≤39 years, good quality Day 4/5 embryo for single-embryo transfer, no uterine fibroids/hydrosalpinx or endometrial polyps). PARTICIPANTS AND SETTING: There were 213 patients in a private IVF unit eligible to be included in the study, with 38 patients (17.84%) having ultrasound diagnosed adenomyosis and 175 patients having no adenomyosis on the scan. Only the first treatment cycle for each patient was included. MAIN RESULTS AND THE ROLE OF CHANCE: The adenomyosis group had a viable clinical pregnancy rate of 23.6% compared with 44.6% in the non-adenomyosis group (P =0.017). However, the median maternal age and duration of infertility of the adenomyosis group was 2 years older and 4 months greater, respectively, than that of the non-adenomyosis group. A logistic regression analysis was performed to account for these differences between the two groups, with the adjusted results still showing a statistically significant decline in viable pregnancy rate in the adenomyosis group (OR = 0.408, CI = 0.181-0.922, P =0.031 when adjusting for maternal age; OR = 0.417, CI = 0.175-0.989, P =0.047 when adjusting for duration of infertility) BIAS, CONFOUNDING AND OTHER REASONS FOR CAUTION: Given the retrospective nature of this study, there is risk of bias. This risk was minimized by having subjective variables such as embryo quality assessed by individuals not involved in the study, while strictly applying the pre-determined inclusion/exclusion criteria to all study participants. Furthermore, it is acknowledged that ultrasound is not a perfect test for the diagnosis of adenomyosis and, therefore, may underestimate the incidence of adenomyosis by misclassifying some patients with mild adenomyosis as not affected. WIDER IMPLICATIONS OF THE FINDINGS: The results of this study should be representative of outcomes for any patient undergoing a GnRH antagonist ovarian stimulation cycle for IVF since standard IVF treatment protocols were used. STUDY FUNDING/COMPETING INTEREST: MSD Australia have provided us with a small amount of funding to cover our costs (including a travel grant for Dr Thalluri to present this work at a conference).