This study investigated the efficacy of CHO via the GnRH-ant protocol combined with FET for treatment of infertility in O-O women with PCOS. In a study population of 398 women with PCOS, the outcomes of pregnancy of 138 O-O women were retrospectively evaluated with reference to the outcomes of 260 N-W women. The results indicated that, compared with the N-W patients, the O-O group had significantly lower rates of embryo implantation, live birth, and live birth of twins, and a significantly higher rate of late abortion. The logistic regression analysis indicated that, of the factors analyzed, only BMI was an independent factor affecting the probability of live birth.
PCOS and overweight/obese are common metabolic disorders associated with subfertility [1,2,3,4,5,6], a recent study observed no significant differences in clinical pregnancy rates between patients with PCOS and those without this syndrome [14]. This appears to indicate that an overweight/obese condition supersedes PCOS as an important factor in female fertility and pregnancy outcomes.
In the year 1998, the World Health Organization determined the overweight and obesity BMI thresholds for Caucasian individuals as 25 kg/m2 and 30 kg/m2, respectively [15]. In 2002, China’s Obesity Working Group proposed adult BMI thresholds of 24.0 and 28 kg/m2 to demarcate an overweight or obese status [11, 12]. In the current study with a Chinese population, we applied a BMI of 24.0 kg/m2 as the demarcation for analysis.
Women in N-W group (n = 265) are almost two times more than O-O group (n = 138) in our study. This result verified a global study showed the percentage of N-W women (63%) are twice as many as O-O women (32%) in China by 2010. While in high-income English-speaking countries and central Afria, the percentages of N-W and O-O are 37% versus 60% and 66% versus 26%, respectively [16]. The overweight/obese is linked to ethnicities, regions, and incomes.
A retrospective cohort study showed that an overweight BMI was no more associated with poor implantation or live-birth rates than normal BMI [17]. However, data regarding the outcomes of IVF/ICSI for patients with PCOS that consider BMI have been inconsistent. For example, O-O patients with PCOS have been reported to have fewer retrieved oocytes, increased rates of miscarriage rates, and lower rates of clinical pregnancy, compared with N-W PCOS patients [18,19,20].
Serum luteinizing hormone, prolactin, and AMH levels putatively reflect ovarian reserve, whereby decreases correlate with reduced quantity and quality of oocytes [21, 22]. In the present study, the GnRH-ant protocol was used to implement COH. Previous study indicated that there are follicle stimulating hormone receptor (FSHR) and estradiol receptor (ER) localized on adipocyte [23, 24]. As a result, compared with the N-W group, the O-O women required significantly higher doses of Gn, and Gn/kg, and longer periods of ovarian stimulation to retrieve the same number of oocytes and good-quality embryos on day 3. The O-O women with significantly lower serum estradiol both on hCG trigger day and before FET. This result is similar to that of Orvieto et al. [19], in which under the GnRH-ant protocol, PCOS patients with BMI ≤ 25 kg/m2 used significantly fewer gonadotrophin ampoules to achieve similar periods of ovarian stimulation and numbers of oocytes retrieved.
In the current study, before FET endometrial preparation was performed under conditions of natural, artificial, or induced ovulation cycles. As Yuan et al. [25] discovered, endometrial thickness is an important and independent predictor of pregnancy outcomes after IVF/ICSI treatment. A meta-analysis also showed that an endometrial thickness cut-off of 7 mm (frequently used) correlates with lower chances of pregnancy [26]. In our data, the endometrial thickness before FET reached 8.4 mm, and was not significantly different between the 2 groups. This reduced the possibility that endometrial factors might have disturbed embryo implantation.
Other factors that influence pregnancy outcomes are quantity and quality of transferred embryos. A meta-analysis that compared blastocyst transfer with cleavage-stage embryo transfer showed that neither had an advantage with regard to rates of clinical pregnancy, ongoing pregnancy, or live births [27]. In our current study, we transferred similar numbers of cleavage-stage or blastocyst frozen-thawed embryos between the 2 cohorts.
Although we found that the O-O patients had significantly lower rates of embryo implantation, live births, live birth twins, compared with the N-W patients, another Chinese scholar found that women with PCOS and BMI ≥ 24 kg/m2 had lower clinical pregnancy rates but similar miscarriage and live birth rates [28]. That study used the standard long GnRH agonist protocol for COH with fresh embryo transfer. In the fresh transfer cycle, women were placed under excessive estrogen and prolactin, which results in ovarian stimulation and can also affect the embryo and endometrial receptivity [29]. In contrast, we chose the GnRH-ant protocol and transfer of frozen-thawed embryos. This is more suitable for patients with PCOS [7, 8], especially because the uterine environment is more natural in the frozen replacement cycle.
In our study, the rate of late abortion was higher in the O-O patients compared with the N-W. We consider that the O-O condition affects embryo implantation.
Our study has the following limitations. First, this is a retrospective study and our results need to be confirmed by randomized controlled trials. Second, in this study we only measured endometrial thickness to evaluate its receptivity. However, to ensure best endometrial receptivity, additional indices such as endometrial patterns and endometrial blood flow should be included. The collection of detailed information regarding pregnancy and neonatal complications will allow us to analyze better the effects of being overweight or obese.