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非不孕女性选择性体外受精(IVF)的经验教训。

Lessons from elective in vitro fertilization (IVF) in, principally, non-infertile women.

机构信息

Center for Human Reproduction, New York, NY 10021, USA.

出版信息

Reprod Biol Endocrinol. 2012 Jun 20;10:48. doi: 10.1186/1477-7827-10-48.

Abstract

BACKGROUND

We here report the first investigation of exclusively elective in vitro fertilization (IVF) cycles in women with no apparent history of infertility. Since IVF outcome in women with infertility are always influenced by underlying causes of infertility, a study on non-infertile women may offer new insights.

METHODS

We investigated 88 females without history of infertility in 109 consecutive elective IVF cycles, almost exclusively performed for purposes of preimplantation genetic screening (PGS; i.e., elective gender selection). The following questions were addressed: (i) impact of PGS on IVF pregnancy chances; (ii) impact of transfer of 1 vs. ≥2 embryos on IVF pregnancy chances; (iii) correlation of anti-Müllerian hormone (AMH) levels to embryo ploidy (iv) effect of gonadotropin dosage used in stimulation on available embryos for transfer; and (v) in form of a 1:1 case control study, compared 33 elective PGS cycles with matched control cycles without PGS, performed in couples with either prior tubal ligations and/or severe male factor infertility as indication of IVF.

RESULTS

The overall clinical pregnancy rate for the group was 36.7%; pregnancy was associated with number of euploid (P = 0.009) and number of embryos transferred (P = 0.001). Odds of pregnancy were 3.4-times higher if ≥4 euploid embryos were produced in comparison to <4 (95% CI 1.2 to 9.2; P = 0.019), and odds of pregnancy were 6.6-times higher if greater than or equal to 2 rather than <1 euploid embryos were transferred (95% CI 2.0 to 21.7; P = 0.002). Increasing AMH (P = 0.001) and gonadotropin dosage used in ovarian stimulation (P = 0.024), was, independently, associated with number of available euploid embryos. Increasing AMH, but not follicle stimulating hormone (FSH), was associated with number of embryos available for biopsy and PGS (P = 0.0001). Implantation rates were 26.4% with PGS and 9.5% without (P = 0.008). Women undergoing PGS, demonstrated 4.58-times higher odds of pregnancy than matched controls (95% CI 1.102 to 19.060, Exp 4.584, P = 0.036).

CONCLUSIONS

This study suggests that outcomes of elective IVF cycles may significantly deviate from infertility-associated cycles. Affirming proof of concept for PGS, utilizing day-3 embryo biopsy and fluorescence in-situ hybridization (FISH), both widely held responsible for earlier failures to establish such proof, suggests that the principal cause of prior failures were likely not insufficient laboratory techniques but poor patient selection for PGS. Such a conclusion questions the current reintroduction of PGS with improved techniques and technologies in absence of prior determination of suited patient populations.

摘要

背景

本研究首次调查了无明显不孕史的女性进行的单纯选择性体外受精(IVF)周期。由于不孕女性的 IVF 结局总是受到不孕原因的影响,因此对非不孕女性进行研究可能会提供新的见解。

方法

我们调查了 109 个连续选择性 IVF 周期中的 88 名无不孕史的女性,这些周期几乎完全用于植入前遗传学筛查(PGS;即选择性性别选择)。提出了以下问题:(i)PGS 对 IVF 妊娠机会的影响;(ii)转移 1 个与≥2 个胚胎对 IVF 妊娠机会的影响;(iii)抗苗勒管激素(AMH)水平与胚胎倍性的相关性;(iv)刺激中使用的促性腺激素剂量对可用于转移的胚胎数量的影响;(v)通过 1:1 病例对照研究,比较了 33 个进行 PGS 的选择性周期和未进行 PGS 的匹配对照周期,这些周期是在有输卵管结扎和/或严重男性因素不孕的夫妇中进行的,这些夫妇是进行 IVF 的指征。

结果

该组的总体临床妊娠率为 36.7%;妊娠与整倍体胚胎数量(P=0.009)和转移胚胎数量(P=0.001)有关。与<4 个整倍体胚胎相比,产生≥4 个整倍体胚胎的妊娠几率高出 3.4 倍(95%CI 1.2 至 9.2;P=0.019),与<1 个整倍体胚胎相比,转移≥2 个而非<1 个整倍体胚胎的妊娠几率高出 6.6 倍(95%CI 2.0 至 21.7;P=0.002)。AMH 的增加(P=0.001)和卵巢刺激中使用的促性腺激素剂量(P=0.024)独立与可获得的整倍体胚胎数量有关。AMH 的增加,但不是卵泡刺激素(FSH)的增加,与活检和 PGS 可用胚胎数量有关(P=0.0001)。PGS 的植入率为 26.4%,无 PGS 的植入率为 9.5%(P=0.008)。进行 PGS 的女性怀孕的几率比匹配的对照组高 4.58 倍(95%CI 1.102 至 19.060,Exp 4.584,P=0.036)。

结论

本研究表明,选择性 IVF 周期的结局可能与不孕相关周期显著不同。证实了利用第 3 天胚胎活检和荧光原位杂交(FISH)进行 PGS 的概念,这两者都被广泛认为是导致早期未能证实这一概念的原因,这表明先前失败的主要原因可能不是实验室技术不足,而是对 PGS 的患者选择不佳。这一结论质疑了当前在缺乏先前确定适合患者人群的情况下,引入改进技术和技术的 PGS。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/975e/3495227/1f22a4c3926a/1477-7827-10-48-1.jpg

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