Department of Gynaecology, Royal Adelaide Hospital, North Terrace, Adelaide, South Australia 5000, Australia.
Hum Reprod. 2012 Dec;27(12):3487-92. doi: 10.1093/humrep/des305. Epub 2012 Sep 20.
Does the presence of ultrasound diagnosed adenomyosis interfere with successful implantation in patients undergoing IVF treatment with GnRH antagonist ovarian stimulation?
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).
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.
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).
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.
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.
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).
经阴道超声诊断的子宫腺肌病是否会影响接受 GnRH 拮抗剂卵巢刺激的 IVF 治疗患者的胚胎成功着床?
经阴道超声诊断的子宫腺肌病与接受 GnRH 拮抗剂刺激的 IVF 治疗患者的优质胚胎着床显著减少有关(活临床妊娠率 23.6%与 44.6%,P=0.017)。
目前对于子宫腺肌病对植入潜能的影响尚无共识。尽管一些研究发现子宫腺肌病患者的子宫内膜环境发生改变,可能影响着床,但也有几篇论文报道其没有相关的生殖缺陷。然而,这些妊娠结局研究主要调查了接受长降调 IVF 方案的患者,在此方案中,在开始卵巢刺激前血清雌激素水平较低(可能使子宫腺肌病失活,并可能否定其对着床的影响)。由于大多数生育诊所现在都倾向于更“患者友好”的拮抗剂方案,在此方案中,患者在开始卵巢刺激前不处于低雌激素状态,因此需要研究 GnRH 拮抗剂刺激的 IVF 治疗中子宫腺肌病是否会影响 IVF 成功率。
这是一项回顾性队列研究,纳入了 748 名患者,他们在 2010 年 4 月至 2012 年 3 月期间接受了经阴道超声筛查,以确定在开始 IVF 治疗前是否存在可能的盆腔病理。在这一组筛查患者中,有 213 名患者符合纳入标准,因为他们没有可能影响胚胎着床的明显子宫或胚胎因素(年龄≤39 岁,有高质量的第 4/5 天胚胎进行单胚胎移植,无子宫纤维瘤/输卵管积水或子宫内膜息肉)。
有 213 名患者符合在一家私人 IVF 单位接受研究的条件,其中 38 名(17.84%)患者经阴道超声诊断为子宫腺肌病,175 名患者超声检查无子宫腺肌病。每个患者仅纳入其第一次治疗周期。
子宫腺肌病组的活临床妊娠率为 23.6%,而非子宫腺肌病组为 44.6%(P=0.017)。然而,子宫腺肌病组的中位母亲年龄和不孕持续时间分别比非子宫腺肌病组年长 2 岁和长 4 个月。进行了 logistic 回归分析以解释两组之间的差异,调整结果仍然显示子宫腺肌病组的活妊娠率有统计学意义的下降(调整母亲年龄时 OR=0.408,CI=0.181-0.922,P=0.031;调整不孕持续时间时 OR=0.417,CI=0.175-0.989,P=0.047)。
偏倚、混杂因素和其他注意事项:由于本研究是回顾性的,存在偏倚的风险。通过让不参与研究的个体评估胚胎质量等主观变量,同时严格按照预定的纳入/排除标准纳入所有研究参与者,将这种风险降到最低。此外,需要承认,超声并不是诊断子宫腺肌病的完美检查方法,因此可能会低估子宫腺肌病的发病率,因为它可能会错误地将一些轻度子宫腺肌病患者归类为未受影响的患者。
由于使用了标准的 IVF 治疗方案,本研究的结果应该能够代表任何接受 GnRH 拮抗剂卵巢刺激周期进行 IVF 的患者的结果。
研究资金/利益冲突:MSD 澳大利亚为我们提供了少量资金以支付我们的费用(包括 Dr Thalluri 参加会议的差旅津贴)。