Department of Obstetrics and Gynecology, Institute of Clinical Sciences, Sahlgrenska Academy, Gothenburg University, 416 84 Gothenburg, Sweden.
IVF Klinikin Reykjavik, Álfheimar 74, 104 Reykjavík, Iceland.
Hum Reprod. 2017 Aug 1;32(8):1621-1630. doi: 10.1093/humrep/dex235.
Does an intensive weight reduction programme prior to IVF increase live birth rates for infertile obese women?
An intensive weight reduction programme resulted in a large weight loss but did not substantially affect live birth rates in obese women scheduled for IVF.
Among obese women, fertility and obstetric outcomes are influenced negatively with increased risk of miscarriage and a higher risk of maternal and neonatal complications. A recent large randomized controlled trial found no effect of lifestyle intervention on live birth in infertile obese women.
STUDY DESIGN, SIZE, DURATION: A prospective, multicentre, randomized controlled trial was performed between 2010 and 2016 in the Nordic countries. In total, 962 women were assessed for eligibility and 317 women were randomized. Computerized randomization with concealed allocation was performed in the proportions 1:1 to one of two groups: weight reduction intervention followed by IVF-treatment or IVF-treatment only. One cycle per patient was included.
PARTICIPANTS/MATERIALS, SETTING, METHODS: Nine infertility clinics in Sweden, Denmark and Iceland participated. Women under 38 years of age planning IVF, and having a BMI ≥30 and <35 kg/m2 were randomized to two groups: an intervention group (160 patients) with weight reduction before IVF, starting with 12 weeks of a low calorie liquid formula diet (LCD) of 880 kcal/day and thereafter weight stabilization for 2-5 weeks, or a control group (157 patients) with IVF only.
In the full analysis set (FAS), the live birth rate was 29.6% (45/152) in the weight reduction and IVF group and 27.5% (42/153) in the IVF only group. The difference was not statistically significant (difference 2.2%, 95% CI: 12.9 to -8.6, P = 0.77). The mean weight change was -9.44 (6.57) kg in the weight reduction and IVF group as compared to +1.19 (1.95) kg in the IVF only group, being highly significant (P < 0.0001). Significantly more live births were achieved through spontaneous pregnancies in the weight reduction and IVF group, 10.5% (16) as compared to the IVF only group 2.6% (4) (P = 0.009). Miscarriage rates and gonadotropin dose used for IVF stimulation did not differ between groups. Two subgroup analyses were performed. The first compared women with PCOS in the two randomized groups, and the second compared women in the weight reduction group reaching BMI ≤ 25 kg/m2 or reaching a weight loss of at least five BMI units to the IVF only group. No statistical differences in live birth rates between the groups in either subgroup analysis were found.
LIMITATIONS, REASON FOR CAUTION: The study was not powered to detect a small increase in live births due to weight reduction and was not blinded for the patients or physician. Further, the intervention group had a longer time to achieve a spontaneous pregnancy, but were therefore slightly older than the control group at IVF. The study only included women with a BMI lower than 35 kg/m2.
The study suggests that weight loss for obese women (BMI: 30-34.9 kg/m2) may not rectify the outcome in IVF cycles, although a significant higher number of spontaneous conceptions occurred in the weight loss group. Also, the study suggests that intensive weight reduction with LCD treatment does not negatively affects the results.
STUDY FUNDING/COMPETING INTEREST(S): The study was funded by Sahlgrenska University Hospital (ALFGBG-70 940), Merck AB, Solna, Sweden (an affiliate of Merck KGaA, Darmstadt, Germany), Impolin AB, Hjalmar Svensson Foundation and Jane and Dan Olsson Foundation. Dr Thurin-Kjellberg reports grants from Merck, non-financial support from Impolin AB, during the conduct of the study, and personal fees from Merck outside the submitted work. Dr Friberg reports personal fees from Ferring, Merck, MSD, Finox and personal fees from Studentlitteratur, outside the submitted work. Dr Englund reports personal fees from Ferring, and non-financial support from Merck, outside the submitted work. Dr Bergh reports and has been reimbursed for: writing a newsletter twice a year (Ferring), lectures (Ferring, MSD, Merck), and Nordic working group meetings (Finox). Dr Karlström reports lectures (Ferring, Finox, Merck, MSD) and Nordic working group meetings (Ferring). Ms Kluge, Dr Einarsson, Dr Pinborg, Dr Klajnbard, Dr Stenlöf, Dr Larsson, Dr Loft and Dr Wistrand have nothing to disclose.
ClinicalTrials.gov number, NCT01566929.
23-03-2012.
DATE OF FIRST PATIENT'S ENROLMENT: 05-10-2010.
在体外受精（IVF）前进行强化减重方案是否会增加肥胖不孕妇女的活产率？
强化减重方案导致了大量体重减轻，但在接受 IVF 的肥胖妇女中，活产率并没有显著提高。
在肥胖妇女中，生育和产科结局受到负面影响，流产风险增加，母婴并发症风险更高。最近的一项大型随机对照试验发现，生活方式干预对肥胖不孕妇女的活产率没有影响。
研究设计、大小和持续时间：这是一项在 2010 年至 2016 年期间在北欧国家进行的前瞻性、多中心、随机对照试验。共有 962 名妇女符合入选条件，其中 317 名妇女被随机分组。采用计算机随机化和隐藏分组，比例为 1:1，分为两组：体重减轻干预组后进行 IVF 治疗或仅进行 IVF 治疗。每个患者包括一个周期。
参与者/材料、地点和方法：瑞典、丹麦和冰岛的 9 家不孕诊所参与了该研究。计划接受 IVF 治疗、BMI≥30 且<35 kg/m²的年龄<38 岁的妇女被随机分为两组：干预组（160 例患者）在 IVF 前进行体重减轻，起始时采用 880 kcal/天的低热量液体配方饮食（LCD）12 周，然后体重稳定 2-5 周，或仅接受 IVF 的对照组（157 例患者）。
在全分析集（FAS）中，体重减轻和 IVF 组的活产率为 29.6%（45/152），仅 IVF 组为 27.5%（42/153）。差异无统计学意义（差异 2.2%，95%CI：12.9 至-8.6，P=0.77）。体重减轻和 IVF 组的平均体重变化为-9.44（6.57）kg，而仅 IVF 组为+1.19（1.95）kg，差异具有统计学意义（P<0.0001）。体重减轻和 IVF 组通过自然妊娠实现的活产数明显更多，分别为 10.5%（16）和仅 IVF 组的 2.6%（4）（P=0.009）。两组的流产率和用于 IVF 刺激的促性腺激素剂量无差异。进行了两项亚组分析。第一项比较了随机分组中患有 PCOS 的妇女，第二项比较了体重减轻组达到 BMI≤25 kg/m²或体重减轻至少 5 BMI 单位的妇女与仅接受 IVF 的组的比较。在这两个亚组分析中，两组之间的活产率均无统计学差异。
局限性、谨慎原因：该研究没有足够的能力检测到体重减轻导致的活产率微小增加，也没有对患者或医生进行盲法处理。此外，干预组实现自然妊娠的时间较长，但在 IVF 时年龄略大于对照组。该研究仅包括 BMI 低于 35 kg/m²的妇女。
该研究表明，肥胖妇女（BMI：30-34.9 kg/m²）的体重减轻可能不会纠正 IVF 周期的结果，尽管体重减轻组的自然妊娠发生率更高。此外，该研究表明，密集的体重减轻与 LCD 治疗不会对结果产生负面影响。
研究资金/利益冲突：该研究由 Sahlgrenska 大学医院（ALFGBG-70 940）、默克公司（Merck AB，索尔纳，瑞典）（默克股份公司的子公司，达姆施塔特，德国）、Impolin AB、Hjalmar Svensson 基金会和简和丹·奥尔森基金会资助。Thurin-Kjellberg 博士报告了来自默克的拨款、在研究期间来自 Impolin AB 的非财务支持以及默克公司的个人酬金，不在提交的工作范围内。Friberg 博士报告了来自 Ferring、Merck、MSD 和 Studentlitteratur 的个人酬金，不在提交的工作范围内。Englund 博士报告了来自 Ferring 的个人酬金和来自 Merck 的非财务支持，不在提交的工作范围内。Bergh 博士报告并获得了以下方面的报酬：每年写两次通讯（来自 Ferring）、演讲（来自 Ferring、MSD、Merck）和北欧工作组会议（来自 Finox）。Karlström 博士报告了来自 Ferring、Finox、Merck 和 MSD 的演讲和北欧工作组会议。Kluge 女士、Einarsson 博士、Pinborg 博士、Klajnbard 博士、Stenlöf 博士、Larsson 博士、Loft 博士和 Wistrand 博士没有需要披露的利益冲突。
ClinicalTrials.gov 编号，NCT01566929。
2012 年 3 月 23 日。
2010 年 10 月 5 日。
