Improved pregnancy rates with luteinizing hormone supplementation in patients undergoing ovarian stimulation for IVF

Introduction

Luteinizing hormone (LH) is believed to play a role in follicle maturation during the natural cycle. However, the need for co-treatment with recombinant LH (rLH) for controlled ovarian stimulation is controversial.

Purpose

The primary objective of our study was to determine if pregnancy rates are improved when rLH is used in addition to rFSH for ovarian stimulation. Secondary outcomes were fertilization rate, implantation rate and live birth rate.

Methods

A retrospective cohort study was performed of 1565 IVF or ICSI cycles. Outcomes were compared between ovarian stimulation cycles from 2007 when rLH and rFSH was used (n = 765) to 2006 when rFSH only was used (n-800).

Results

Improved outcomes were found for rLH + rFSH versus rFSH alone for; pregnancy rate (61% and 54% respectively, p = 0.006), live birth rate (49% and 42% respectively, P = 0.01), fertilization rate (74% versus 72% respectively, p = 0.04 and implantation rate (41% versus 37% respectively, p = 0.03).

Conclusions

Our large retrospective cohort study showed an improved pregnancy rate and live birth rate with rLH supplementation. This was associated with an improved fertilization and implantation rate and therefore may reflect an improvement in oocyte quality and/or uterine receptivity.     

改良GnRH-a长方案在控制性促排卵中的应用

目的探讨改良GnRH—a/FSH/hMG联合长方案在控制性促排卵中的应用以及国产阿拉瑞林在此方案中的使用。方法以回顾性分析的方法对174例改良GnRH-a长方案和48例超短方案控制性促排卵的资料进行回顾性分析。结果 改良GnRH—a/FSH/hMG联合长方案在FSH/hMG用药天数、用药量、取卵数、移植数、冻存胚胎数、hCG丑内膜厚度、临床妊娠率、种植率、流产率、OHSS发生率等方面与短方案组相比差异均无显著性(P>0.05),其中流产率明显低于超短方案组。结论改良国产阿拉瑞林/FSH/hMG联合长方案是一种简单、经济、有效的控制性促排卵方案,值得在IVF—ET周期中推广。     

Conversion of ICSI cycles to IUI in poor responders to controlled ovarian hyperstimulation

AimComparison between the results of the oocyte retrieval technique and the conversion to the intra-uterine insemination (IUI) technique in cases with poor ovarian response to the controlled ovarian hyperstimulation (COH) procedure.Patients and methodsIt is a retrospective observational study in women with poor ovarian response to COH which is defined as estradiol (E2) peak level <1000 pg/mL or with ?4 follicles which are ?14 mm in diameter. Four hundred and sixteen cases were reported as poor responders in 2 IVF centers since December 2007 to July 2010. One hundred and fifty two cases of them proceeded to the oocyte retrieval procedure. These cases were assigned as group (A). Sixty eight cases converted to IUI and were assigned as group (B). One hundred and ninety six cases canceled their cycles. These cases were not included in the current study. Our data were collected from the databases of two In Vitro Fertilization (IVF) centers and analyzed retrospectively to compare the results of the different applied techniques in the studied groups. The main measured outcome parameters were the clinical pregnancy rate and the live birth rate.ResultsThe group of cases proceeded to the oocyte retrieval procedure had a higher basal Follicle Stimulating Hormone (FSH) level, needed a longer duration of stimulation with higher Human Menopausal Gonadotropin (HMG) doses and had higher E2 peak levels. The clinical pregnancy rates and the live birth rates were higher in the group proceeded to the oocyte retrieval than the group converted to IUI but the difference was not statistically significant.ConclusionAs the pregnancy rates difference between both groups was not statistically significant the conversion to IUI could be considered a useful substitute to the oocyte retrieval procedure in the poor responder cases. However, to adopt this conclusion, further confirmation in other prospective studies with larger sample size is a must.     

卵巢慢反应患者控制性超促排卵相关因素分析:一项多中心回顾性研究

目的探讨控制性超促排卵(COH)过程中发生卵巢慢反应可能的相关因素。方法回顾性分析2014年1月—2016年1月期间于兰州大学第一医院、新疆佳音医院、青海省人民医院、银川市妇幼保健院、广西玉林市妇幼保健院进行促性腺激素释放激素激动剂(GnRH-a)长方案体外受精-胚胎移植(IVF-ET)的144例卵巢慢反应患者的临床资料,与132例卵巢正常反应患者(正常对照组)进行对比。结果与正常对照组相比,慢反应组患者体质量指数(BMI)、促甲状腺激素(TSH)较高,降调节及促排卵时间较长,促性腺激素(Gn)使用后7d平均卵泡直径偏小,雌二醇(E_2)、黄体生成素(LH)低,hCG注射日E_2低,IVF双原核(2PN)卵裂率较高,临床妊娠率低,差异均有统计学意义(P0.05)。患者年龄、不孕年限、基础卵泡刺激素(FSH)、LH、催乳素(PRL)、E_2、基础卵泡数、hCG注射日孕酮(P)、获卵率、胚胎质量、胚胎种植率、流产率、宫外孕率、继续妊娠率及取消移植率组间均无统计学差异(P0.05)。结论卵巢慢反应可能与患者BMI过高、甲状腺功能降低及GnRH-a过度抑制相关,较长的Gn天数仍可使慢反应患者获得较好的妊娠结局。     

IVF中三种促超排卵方案效果的比较

目的：探讨IVF中最佳促超排卵方案。方法：将IVF对象随机分为3组。BFh组：23例126个周期,按BFh长方案（Buserelin／FSH／hCG）进行;Chh组：13例14个周期,以CC／hMG／hCG方案进行;Fhh组：55例57个周期,按FSH／hMG／hCG方案进行。结果：每周期平均促性腺激素（Gn）用量BFh组为18．62±5．95支;Chh组16．57±5．70支;Fhh组25．56±8．08支。每周期获成熟卵子数分别为10．23±5．80个;6．07±3．22个;10．96±6．45个。Gn用量BFh组与Chh组差异无显著性（P＞0．05）,但取到的卵子数,差异有显著性（P＜0．05）。BFh组与Fhh组比较,BFh组Gn用量少于Fhh组（P＜0．05）,但取到的卵子数差异无显著性（P＞0．05）,且BFh组无过早的LH峰出现,另二组则各有1例过早的出现内源性LH峰。结论：IVF中BFh方案是较为理想的促起排卵方案。     

Estradiol level on day 9 as a predictor of risk for ovarian hyperresponse during controlled ovarian hyperstimulation

Purpose : To investigate the estradiol (E₂) level in the mid-follicular phase during controlled ovarian hyperstimulation (COH) and evaluate it as a predictor of a high risk for ovarian hyperresponse. Methods : From January 1996 to October 2001, the records of a total of 146 patients undergoing 164 COH cycles were retrospectively reviewed. All patients received the long protocol of GnRH agonists from the previous mid-luteal phase and then hMG or FSH from day 3 of the menstrual cycle. The E₂ level was evaluated on day 9. Ovarian hyperresponse was defined as 1) an E₂ level on the day of hCG injection was >4000 pg/mL, or 2) the necessity for coasting during COH to decrease the risk of ovarian hyperstimulation syndrome (OHSS). Results : Of the 52 cycles in which day 9 E₂ level was >800 pg/mL, 29 (55.8%) fulfilled the criteria for ovarian hyperresponse. None of patients whose day 9 E₂ level was <300 pg/mL met the criteria for hyperresponse. The pregnancy rate in the groups with day 9 E₂ level <300 pg/mL was 42.9%; for an E₂ level = 300–800 pg/mL, 49.2%; and for an E₂ level >800 pg/mL, 32.7%. The corresponding implantation rates were 18.8, 28.0, and 17.0%. The E₂ level on day 9 did not correlate with clinical pregnancy rates or implantation rates. Conclusions : A high E₂ level in the mid-follicular phase was predictive of patients with a high ovarian response. An E₂ level on day 9 of menstrual cycle of >800 pg/mL suggests an increased risk for ovarian hyperresponse, and appropriate management should be instituted to decrease the risk of OHSS.     

Controlled ovarian hyperstimulation interventions in infertile women aged 40 years or older undergoing in vitro fertilization

Background

The success of in vitro fertilization (IVF) treatment depends on adequate follicle recruitment following controlled ovarian hyperstimulation (COH). Women aged 40 years or older have a reduced ovarian reserve and various treatment protocols have been proposed that aim to increase their ovarian response.

Objectives

To compare the effectiveness of different COH treatment interventions in women undergoing IVF aged 40 years or older.

Search strategy

MEDLINE, the Cochrane Library, and the Chinese Biomedical database were searched for randomized controlled trials (RCTs).

Selection criteria

Only RCTs comparing one type of COH intervention with another in women undergoing IVF aged 40 years or older were included.

Data collection and analysis

Two authors independently searched the abstracts, identified relevant papers, assessed inclusion and trial quality, and extracted the relevant data.

Main results

Four trials involving 4 different comparison groups were included in the review and enrolled a total of 611 randomized subjects.

Conclusion

There was insufficient evidence to support the routine use of any particular COH intervention to manage infertile women aged 40 years or older undergoing IVF. More robust data from good quality RCTs with relevant outcomes are needed.     

Growth hormone co-treatment on controlled ovarian stimulation in normal ovarian response women can improve embryo quality

To investigate the clinical efficacy of growth hormone (GH) in normal response patients with poor embryo quality in previous in vitro fertilization cycles. A total of 1562 infertile women were enrolled in this matched case–control study: 781 women were treated with GH (study group), whereas 781 matched patients were treated without GH (control group). GH was administered by a daily subcutaneous injection of 2 or 4?IU started from either D2 of the previous cycle (6?weeks GH pretreatment) or the initial day of controlled ovarian stimulation (2?weeks GH pretreatment) until hCG trigger. The study group was further divided into four subgroups: 2?IU-6 weeks GH pretreatment, 4?IU-6 weeks GH pretreatment, 2?IU-2 weeks GH pretreatment, and 2?IU-4 weeks GH pretreatment. Patients receiving GH showed significantly lower Gn dosage. The total number of oocytes retrieved, embryos formed, endometrial thickness on hCG day were significantly higher with GH. 2PN rate and high-quality embryo rate were lower in the GH group. However, GH increased clinical pregnancy rate with significant difference. 4?IU-6 weeks GH pretreatment showed lowest duration of Gn and highest clinical pregnancy rate compared with other three groups. Number of transferred embryos was confounding factor both in univariate and multivariate analysis. Our study showed that co-treatment with GH in patients with normal ovarian response could increase pregnancy rate.     

Ovarian response to controlled ovarian hyperstimulation in women with cancer is as expected according to an age-specific nomogram

Purpose

To evaluate the ovarian response to controlled ovarian hyperstimulation (COH) in cancer patients according to an age-specific nomogram for the number of retrieved oocytes.

Methods

Retrospective observational study carried out in a University affiliated fertility clinic. Forty-eight patients with cancer underwent ovarian stimulation for oocyte cryopreservation. An age - specific nomogram for the number of retrieved oocytes was built with 1536 IVF cycles due to male factor exclusively, oocyte donation and age related fertility preservation. The number of oocytes retrieved in cancer patients was compared to the expected response according to the nomogram using the Z-score.

Results

The mean number of total retrieved oocytes in patients with cancer was 14.04 ± 8.83. After applying the Z-score to compare the number of retrieved oocytes between women with cancer and the expected response according to the age-specific nomogram, we did not observe a statistically significant difference (Z-score 0.23; 95 % CI [−0.13-0.60]).

Conclusion(s)

According to our results, patients with cancer exhibit an ovarian response as expected by age. Despite the limitation of the sample size, the obtained results should encourage oncologists for early referral of women with cancer to fertility specialists.     

不同年龄段不孕患者控制性超排卵中卵巢低反应的预测

目的研究不同年龄段不孕患者超排卵过程中卵巢低反应的发生情况,探讨不同年龄段患者卵巢低反应的相关因素及比较各预测指标的诊断价值。方法回顾性分析中山大学附属孙逸仙医院生殖医学中心2424个体外受精/卵细胞浆内单精子注射（IVF/ICSI）周期。按年龄分为4组,比较各组卵巢低反应的发生率及妊娠率;logistic回归分析基础FSH、基础LH、基础E2、窦卵泡数（AFC）、卵巢容积和BMI等与卵巢低反应的相关性,并根据回归结果计算联合指标的ROC曲线。结果 18～30岁组不孕患者卵巢低反应率为9.0%（77/852）,基础FSH与AFC联合预测卵巢低反应的ROC曲线下面积为0.726;31～35岁组卵巢低反应率为19.7%（172/871）,基础FSH、基础LH、AFC联合预测卵巢低反应的ROC曲线下面积为0.789;36～40岁组卵巢低反应率34.9%（190/545）,基础FSH、卵巢体积、AFC和年龄联合预测卵巢低反应的ROC曲线下面积为0.831;≥41岁组卵巢低反应率为69.2%（108/156）,AFC预测卵巢低反应的ROC曲线下面积为0.809。结论随着年龄增大,卵巢低反应发生率增加、妊娠率下降;不同年龄段预测卵巢低反应的指标不同,综合多指标的预测价值较单一指标预测价值高,建议综合多个有效指标评估卵巢的反应性。     

The effect of multiple cycles in oocyte donors

OBJECTIVE: The purpose of this study was to determine whether multiple controlled ovarian hyperstimulation cycles in oocyte donors affect the ovarian response, the oocytes retrieved, or the pregnancy rates. STUDY DESIGN: A retrospective chart review of repeat donor in vitro fertilization cycles between 1992 and 2003 at the University of Cincinnati Center for Reproductive Health was performed. The variables that were examined included the peak estradiol level, the length of stimulation, the number of follicles >15 mm, the amount of gonadotropins that were used, the number of oocytes that were retrieved and inseminated, the average number of cells per embryo at the time of transfer, and the clinical pregnancy rates. RESULTS: A total of 107 in vitro fertilized donor oocyte cycles were analyzed, of which 45 young healthy women underwent at least 2 cycles and 17 women underwent 3 cycles. Donors who underwent a second or third cycle demonstrated no differences in the cycle parameters that were observed. CONCLUSION: Repeated controlled ovarian hyperstimulation cycles in a donor population does not demonstrate a diminished ovarian response to exogenous gonadotropins. Oocyte donors can undergo up to 3 stimulation cycles without a negative affect on the ovarian response to gonadotropins, the number of mature oocytes retrieved, the embryo quality, or the clinical pregnancy rate.     

Growth hormone co-treatment within a GnRH agonist long protocol in patients with poor ovarian response: a prospective,randomized, clinical trial

Objective The efficacy of growth hormone co-stimulation to long luteal GnRHa regimen in poor responders to COH for IVF was assessed. Methods This prospective, randomized, clinical trial was performed in a private assisted reproduction center. The study involved 61 patients who responded poorly to high dose gonadotropin treatment in their first cycles in the same center. Study group of 31 patients were given growth hormone co-treatment, daily subcutaneous injection of 4 mg from day 21 of preceding cycle along with GnRHa, until the day of hCG. Control group of 30 patients received the same treatment protocol except the growth hormone co-treatment. Primary end-point of the study was the number of oocytes fertilized whereas the pregnancy rate was the secondary end-point. Results Patients’ demographic characteristics did not differ significantly between the two groups. 2PNs in growth hormone co-treatment group was significantly higher than the control group (4.4 ± 1.8 vs 1.5 ± 0.9, p < 0.001). Although more pregnancies and more clinical pregnancies with fetal heart beat were achieved in growth hormone group (12/31), compared to the control group (6/30), the difference did not reach to statistical significance. Conclusion Poor responder women undergoing repeated assisted reproduction treatment and co-stimulated with GH achieve more oocytes, higher fertilization rate if growth hormone started in the luteal phase of previous cycle, as compared with women of the same status treated with GnRHa long protocol. The study was unable to show that clinical pregnancy rate was increased significantly.     

血清抑制素水平在体外受精-胚胎移植超排卵周期中预测卵巢反应性的价值

目的探讨血清抑制素水平在体外受精-胚胎移植(IVF-ET)超排卵周期中与卵巢反应性的相关性及其预测价值。方法对37例初次接受IVF-ET、基础卵泡刺激素(FSH)水平<12U/L的患者,于IVF前1周期月经第2~4天及黄体中期、IVF周期重组rFSH注射第5天、人绒毛膜促性腺激素(hCG)注射日、取卵日及黄体中期,分别检测血清雌二醇、孕酮、抑制素(INH)A及INHB水平。根据IVF周期中的获卵数、雌二醇峰值水平、是否发生卵巢过度刺激综合征(OHSS)的情况,将37例患者分为卵巢低反应者8例(A组)、卵巢正常反应者及卵巢高反应者29例(B组),比较两组IVF-ET临床效果及注射rFSH前后INH、雌二醇及孕酮水平的变化。通过多重逻辑回归分析、受试者工作特征曲线分析,评价各激素水平预测卵巢反应性的准确性;通过敏感度、特异度的计算确定INHB诊断的临界值。结果(1)A、B组IVF前1周期月经第2~4天INHB水平分别为(37±35)、(91±90)ng/L;IVF周期注射rFSH第5天的INHB水平分别为(194±157)、(2254±4765)ng/L,INHA水平分别为(36±35)、(91±90)ng/L,两组比较,差异有统计学意义(P<0·05)。(2)获卵数与IVF前1周期月经第2~4天INHB水平、IVF周期rFSH注射后各阶段的INHB、INHA及雌二醇水平呈显著正相关(INHB:r=0·39~0·67,P<0·05;INHA:r=0·43~0·59,P<0·01;雌二醇:r=0·50~0·60,P<0·01)。(3)受试者工作特征曲线分析显示,注射rFSH第5天的INHB水平的最大的曲线下面积为0·948(95%可信限为0·871~1·025),将INHB为400ng/L作为临界值时,其对卵巢反应性的预测敏感度为82·8%,特异度为99·1%。结论基础INHB水平、IVF周期rFSH注射第5天的INHB水平均是预测卵巢反应性较好的标记物;IVF周期rFSH注射第5天的INHB水平对卵巢反应性具有最佳的预测价值。     

Studies on the effects of initial injection doses of follicle stimulating hormone on the pregnancy and the ovarian hyperstimulation syndrome incidence in polycystic ovarian syndrome patients

Background:  Patients with polycystic ovarian syndrome (PCOS) are often resistant to clomiphene citrate, which causes the need for subsequent gonadotropin treatment. However, careful administration is required because of the potential side-effects, that is, ovarian hyperstimulation syndrome (OHSS) and multiple pregnancy.
Methods:  Forty-three cycles in 22 patients with PCOS were enrolled in this study. Ovarian stimulation was initiated on day 7 of the menstrual cycle with 150 IU/day of follicle stimulating hormone (FSH; 150 IU course), 100 IU/day (100 IU course), and 75 IU/day (75 IU course), successively. If follicles over 12 mm in diameter did not develop after 1 week, the dose was increased. In each treatment course, the number of developed follicles, the serum estradiol level before ovulation, total FSH dosage and duration of administration, the incidence of OHSS, and pregnancy rate were examined.
Results and Conclusion:  The largest number of developed follicles and the highest serum estradiol level were found in the 150 IU course. In contrast, the total FSH dosage and duration of administration were highest and longest in the 75 IU course. The incidence of OHSS and pregnancy rate were highest in the 150 IU course and in the 75 IU course, respectively. The present study indicates that 100 IU or 75 IU of FSH is recommended as an initial injection dose for PCOS patients. (Reprod Med Biol 2003; 2 : 63–67)     

血清性激素含量与体外受精-胚胎移植结局的关系分析

目的 探讨在控制性超排卵中血清性激素变化与妊娠结局的关系。方法 随机选择兰州大学第一医院辅助生殖医学中心2003—2004已接受试管婴儿技术治疗，采用黄体期长方案进行控制性超排卵临床妊娠病例147例，未妊娠140例，分析比较组间各项观察指标。结果 两组间患者降调节时间、促性腺激素（Gn）总量、募集卵泡数、获卵数、MII卵数差异均有显著性（P〈0．05），HCG注射日血清孕酮（P）值、血清雌二醇／孕酮（E2／P）比值差异有显著性（P〈0．05）；促性腺激素释放激素激动剂（GnRH—a，达菲林）用量、Gn天数差异无显著性（P〉0．05），降调节后血清黄体生成素（LH）、HCG注射日血清E2、取卵日血清E2、胚胎移植日血清催乳激素（PRL）水平差异无显著性（P〉0、05）。结论 在控制性超排卵治疗中，观察调控血清性激素含量至关重要。HCG注射日血清P值、E2／P比值是预测助孕结局的重要指标，血清E2／P值在1．32—6．11，血清P值在0．637—1.645μg/L时，临床妊娠率增加。     

Low dose gonadotropin-releasing hormone agonist treatments with early discontinuation for controlled ovarian hyperstimulation in an<Emphasis Type="Italic">in vitro</Emphasis> fertilization program

Aim:  The purpose of the present study was to investigate the applicability of a protocol for controlled ovarian hyperstimulation (COH) featuring early discontinuation of low dose gonadotropin-releasing hormone agonist (GnRHa) for ovulation induction for in vitro fertilization (IVF).
Methods:  Four hundred and eighty-seven women undergoing 555 IVF cycles were recruited into the study. Controlled ovarian hyperstimulation was achieved by using either a short protocol of low dose GnRHa (for 5 days only; groups 1 and 2) or a modified long protocol with early discontinuation of GnRHa (groups 3 and 4). Groups 1 and 3 received urinary follicle-stimulating hormone (FSH) and groups 2 and 4 received recombinant FSH. Oocyte retrieval was performed 34 to 36 h after human chorionic gonadotropin (hCG) injection, followed by embryo transfer 3 days later.
Results:  Luteinizing hormone (LH) levels on the hCG injection day were lower with the modified long protocol (groups 3 and 4) than with the short 5-day treatment (groups 1 and 2). There were higher LH levels in group 1 than in groups 2, 3 and 4, resulting in a worse fertilization rate and clinical pregnancy rate. There were no statistically significant differences between groups 2, 3 and 4 in the rates of fertilization, clinical pregnancy and delivery. A higher estradiol (E₂) level in group 3 than in groups 1, 2 and 4 resulted in a worse implantation rate.
Conclusion:  Early cessation of GnRHa may not induce a premature LH surge in controlled ovarian hyperstimulation, while a low dose also offers a useful alternative to a long protocol of IVF. Ovarian stimulation with recombinant follicle-stimulating hormone (rFSH) is considered to be favorable in this low dose GnRHa treatment. (Reprod Med Biol 2003; 2 : 25–30)     

Gonadotropin releasing hormone antagonist use in controlled ovarian stimulation and intrauterine insemination cycles in women with polycystic ovary syndrome

Objective

To evaluate the effect of the GnRH antagonist on gonadotropin ovulation induction in women with PCOS.

人绒毛膜促性腺激素注射日血清孕酮水平对体外受精妊娠结局的影响

目的:探讨在控制性超排卵中,HCG注射日孕酮水平与体外受精妊娠结局的关系。方法:回顾性分析2009年6月~2010年5月在我院生殖中心采用长方案垂体降调节行体外受精助孕的1145个周期。按照HCG注射日血清孕酮水平的不同分为四组,A组:血清孕酮<0.9ng/ml者313周期;B组:血清孕酮0.9~1.5ng/ml者411周期;C组:血清孕酮1.5~2.5ng/ml者337周期;D组:血清孕酮≥2.5ng/ml者84周期。结果:D组(P≥2.5ng/ml)种植率和临床妊娠率明显降低,异位妊娠率明显升高,与其余各组比较有统计学意义(P<0.05),而各组间受精率、卵裂率、优胚形成率及冻融胚胎移植周期临床妊娠率差异无统计学意义。结论:控制性超排卵中,HCG注射日孕酮升高仅影响了新鲜周期的妊娠结局,而不影响解冻周期的妊娠率。因此,高孕酮水平患者可考虑放弃新鲜胚胎移植,行全胚胎冷冻。     

Comparison of the efficacy and safety of a new recombinant human follicle-stimulating hormone (DA-3801) with follitropin-alpha (Gonal-F) in women undergoing controlled ovarian hyperstimulation for assisted reproductive technology

AIM: To compare the efficacy and safety of a new recombinant human follicle-stimulating hormone (FSH; DA-3801) with follitropin-alpha (Gonal-F) in women undergoing controlled ovarian hyperstimulation (COH) for assisted reproductive technology (ART). METHODS: This was a phase III, multicenter, randomized, non-inferiority study. A total of 97 women were randomized to receive COH using DA-3801 (DA-3801 group, n = 49) or Gonal-F (Gonal-F group, n = 48). All subjects underwent COH using a gonadotropin-releasing hormone (GnRH) antagonist protocol. The primary efficacy endpoint was the number of oocytes retrieved, and the secondary efficacy endpoints included the total dose of FSH, the duration of stimulation, the serum estradiol levels on the day of human chorionic gonadotropin (hCG) administration, and the fertilization, implantation and pregnancy rates. Safety was evaluated using pre- and post-treatment laboratory tests and all adverse events were recorded. RESULTS: The number of oocytes retrieved was 13.0 +/- 6.2 (DA-3801) versus 10.6 +/- 6.7 (Gonal-F) in the intention-to-treat (ITT) population, and 12.7 +/- 6.4 (DA-3801) versus 11.0 +/- 7.1 (Gonal-F) in the per-protocol (PP) population. The non-inferiority of DA-3801 was demonstrated with differences of 2.3 +/- 6.5 (95% confidence interval [CI] = 0.13, infinity) and 1.7 +/- 6.7 (95% CI = -0.74, infinity), respectively, in the ITT and PP populations. The total dose of FSH used (1789.8 +/- 465.5 vs 2055.6 +/- 646.7 pg/mL, P = 0.027) and duration of stimulation (8.3 +/- 1.4 vs 9.1 +/- 1.9 days, P = 0.036) in the ITT population were significantly lower in the DA-3801 group. Other secondary efficacy endpoints, including pregnancy and implantation rates and the incidence and severity of adverse events, were comparable between the two groups. CONCLUSIONS: The results of this study demonstrate that DA-3801 is not inferior to follitropin-alpha in terms of its efficacy and safety in women undergoing COH for ART.