Department of Reproductive Medicine, Dexeus University Hospital, Gran Via de Carles III, 71-75, Barcelona 08022, Spain.
Department of Reproductive Medicine, Conceptum - Unidad de Fertilidad del Country Conceptum, Bogotá 110221, Colombia.
Hum Reprod. 2020 Apr 28;35(4):826-836. doi: 10.1093/humrep/dez299.
Are there any differences in the fresh (LB) and cumulative live birth rates (CLBR) of women undergoing controlled ovarian stimulation (COS) for IVF/ICSI following pretreatment with different types of oral contraceptive pills (OCP) for different durations as compared to no-OCP?
OCP administration for an interval of 12- to 30-day treatment period and with a 5-day washout period does not affect clinical pregnancy, LB nor cumulative LB in patients undergoing COS for an IVF cycle.
The use of OCP is an effective way of treatment planning in IVF/ICSI cycles, but published evidence about its effect on pregnancy and LBR is inconsistent, some studies finding decreased rates but others no difference.
STUDY DESIGN, SIZE, DURATION: This is a retrospective analysis carried out in a University-affiliated tertiary centre between January 2009 and December 2017. Overall, 4116 infertile women between 18 and 45 years, who underwent their first ovarian stimulation cycle in our centre, were included.
PARTICIPANTS/MATERIALS, SETTING, METHODS: Patients were categorised into two groups as receiving OCP (n = 3517) or not (no OCP, n = 599). All patients with OCP pretreatment initiated controlled ovarian stimulation (COS) 5 days post-pill. Overall, two types of OCP were used at the study's centre: ethinylestradiol (EE) 30 μg/desogestrel 150 μg, a third-generation progesterone; or EE 30 μg/drospirenone 3 mg, a fourth-generation progestin with mild antiandrogenic activity.
A total of n = 4116 patients were analysed, (OCP n = 3517 and non-OCP n = 599). The use of OCP was independently associated with a small increase in the number of oocytes retrieved after adjusting for age, BMI, use of OCP, cause of infertility, initial dose (IU), type of gonadotropin, stimulation days, total stimulation units (total IU) (β 0.22, 95% CI 0.12-0.31). Cumulative LBRs were comparable between groups OCP versus non-OCP (32.4 versus 31.6%, P = 0.712). Following adjustment for age, BMI, infertility diagnosis, starting and total dose, type of gonadotropin, total days of stimulation, type of insemination, number of oocytes retrieved, day of transfer and number of embryos transferred in a multiple logistic analysis, patients using OCPs had a similar probability of achieving a LB as compared with patients not-using OCPs following fresh embryo transfer (ORadj 0.89, 95% CI 0.69-1.15) and a similar probability for CLBR after the use of fresh and frozen embryos (ORadj 0.94, 95% CI 0.73-1.21). No differences were observed in ovarian stimulation and clinical outcomes between drospirenone and desogestrel OCP groups.
LIMITATIONS, REASONS FOR CAUTION: Limitations are related to the retrospective nature of the study; despite the sample size, the adjustments and the multivariable regression analysis conducted, we cannot exclude the presence of confounding bias. OCP administration was not randomly assigned, not allowing to exclude the presence of selection bias. Lastly, we only used two types of OCP with durations and washout periods as per institution protocol. Therefore, we cannot exclude that longer duration of administration, a different type of OCP or different pill-free interval might have had an alternative effect on LBR or CLBR; thus, the generalizability of this study's results should be considered with caution.
Our study provides reassuring evidence that the use of 12-30 days OCP for cycle programming, prior to IVF, does not decrease the chance of live birth and cumulative live birth rates.
STUDY FUNDING/COMPETING INTEREST(S): No external funding was used for this study. This research was performed under the auspices of 'Càtedra d'Investigació en Obstetrícia I Ginecologia' of the Department of Obstetrics, Gynaecology and Reproductive Medicine, Hospital Universitario Dexeus, Universitat Autònoma de Barcelona. The authors report no conflict of interest associated with the current study.
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与未服用口服避孕药（OCP）相比，预处理不同时长（12-30 天）和停药期（5 天）的不同类型 OCP 对行体外受精/卵胞浆内单精子注射（IVF/ICSI）的控制性卵巢刺激（COS）的女性，其新鲜（LB）和累积活产率（CLBR）是否存在差异？
OCP 治疗方案为 12-30 天，停药期 5 天，不会影响行 IVF 周期 COS 的患者的临床妊娠、LB 或累积 LB。
OCP 的使用是 IVF/ICSI 周期治疗计划的有效方法，但关于其对妊娠和 LBR 影响的已发表证据不一致，一些研究发现降低了活产率，而另一些研究则没有差异。
研究设计、规模、持续时间：这是一项在 2009 年 1 月至 2017 年 12 月期间在大学附属三级中心进行的回顾性分析。共有 4116 名 18-45 岁接受中心首次卵巢刺激周期的不孕女性纳入研究。
参与者/材料、地点、方法：患者分为服用 OCP（n=3517）和未服用 OCP（n=599）两组。所有预处理服用 OCP 的患者在停药 5 天后开始接受控制性卵巢刺激（COS）。研究中心使用的 OCP 有两种类型：第三代孕激素炔雌醇（EE）30μg/屈螺酮 150μg；或第四代孕激素屈螺酮 3mg/二氢孕酮 3mg，具有轻度抗雄激素活性。
共分析了 4116 名患者（OCP n=3517，非 OCP n=599）。调整年龄、BMI、OCP 使用情况、不孕原因、初始剂量（IU）、促性腺激素类型、刺激天数、总刺激单位（总 IU）后，OCP 的使用与获得的卵母细胞数量增加独立相关（β0.22，95%CI 0.12-0.31）。两组的累积活产率（LB）无差异（OCP 组 32.4%，非 OCP 组 31.6%，P=0.712）。在多变量逻辑分析中，调整年龄、BMI、不孕诊断、起始和总剂量、促性腺激素类型、刺激天数、授精类型、获卵数、移植日和移植胚胎数后，使用 OCP 的患者与未使用 OCP 的患者相比，进行新鲜胚胎移植后的活产率（ORadj 0.89，95%CI 0.69-1.15）和新鲜胚胎与冷冻胚胎使用后的累积活产率（ORadj 0.94，95%CI 0.73-1.21）相似。在卵巢刺激和临床结局方面，屈螺酮和去氧孕烯 OCP 组之间无差异。
局限性、谨慎原因：研究的局限性与回顾性研究的性质有关；尽管样本量较大，并且进行了调整和多变量回归分析，但我们不能排除存在混杂偏倚的可能性。OCP 的给药不是随机分配的，不能排除存在选择偏倚的可能性。最后，我们仅使用了两种持续时间和停药期按机构方案的 OCP。因此，我们不能排除更长的给药时间、不同类型的 OCP 或不同的停药期可能对 LB 或 CLBR 有不同的影响；因此，应谨慎考虑本研究结果的普遍性。
我们的研究提供了令人安心的证据，表明在 IVF 前进行 12-30 天的 OCP 治疗方案不会降低活产的机会和累积活产率。
研究资金/利益冲突：本研究无外部资金支持。该研究是在巴塞罗那自治大学 Dexeus 医院妇产科的“产科和妇科研究主席”的主持下进行的。作者报告与当前研究没有利益冲突。
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