Objective: to evaluate the impact of pre-gestational maternal age and body weight on the outcome of IVF in women with PCOS.  
Design: a retrospective study on women with PCOS undergoing IVF.
Methods: Medical records of 200 known cases of polycystic ovary syndrome women treated in a third level referral center by the same therapeutic protocol were evaluated retrospectively. Demographic data, maternal body mass index, hormonal profile (LH, FSH, estradiol, anti-mullerian), IVF cycle parameters and outcome were documented. Patients were classified to three groups based on their body mass index (Normal: 18.5-24.9, overweight: 25-30, obese≥30). IVF cycle parameters and outcome were compared in these 3 groups. Effect of age was also evaluated by comparing the results in patients aged <35 and ≥35.
Results: Mean age of patients was 32.5 (±5.2). 72 patients had normal BMI, 85 patients were overweighed and 43 cases were obese. Baseline hormonal profile was similar in 3 groups. Total dose of administered FSH were similar in 3 groups. Number of retrieved oocytes was statistically significant higher in patients with BMI>30 but the number of mature oocytes and number of embryos were statistically lower in this group. Size of follicles showed no statistically significant difference in 3 groups. Clinical pregnancy rate was statistically significant lower in patients with BMI>30 kg/m2 and age>35 years old.
Conclusions: BMI>30 and age >35 years old has a statistically significant negative impact on IVF success rate.

Ovulatory dysfunction is seen in about 6% of women with infertility [1]. In about 70% of cases, polycystic ovary syndrome (PCOS) is the main cause of ovulation failure [2]. PCOS is the most common hormonal disorder in women of reproductive age [3] with a prevalence of 6-10% which leads to hypergonadism, anovulation, and increased level of luteinizing hormone (LH), increased risk of early abortion, diabetes, hyperlipidemia, hypertension /cardiovascular disease, and obesity (4-5). Up to 65% of women with PCOS are overweighed or obese [6] and a body mass index (BMI) ≥30 kg/m2 is seen in >50% of cases [7].
In-vitro fertilization (IVF) is a common therapeutic modality used in infertile women. IVF has different success rates in different subgroups of patients and it is necessary to alter the common standard protocols to overcome the potential obstacles in some populations of patients and achieve the best results [8]. Although according to some studies, obesity per se or as a part of PCOS status of patient may decrease the fertilization rate and clinical pregnancy chance after IVF (probably by decreasing the oocyte count and increasing the gonadotropin resistance) but the results of different studies are still conflicting [9]. 
This study was conducted to evaluate the impact of pre-gestational maternal age and body weight on the outcome of IVF in women with PCOS.  

Study design and setting
This retrospective study was conducted in a tertiary level referral teaching hospital with annual censuses of about 40,000. We enrolled cases from November 2016 to April 2018 conveniently. Institutional ethics committee approved our study (Code: IR.SBMU.MSP.REC.1398.070). The study was carried out in accordance with the Declaration of Helsinki (1989). Informed written consent was obtained from all patients.
Participants
All <40>
Study Protocol
Diagnosis of PCOS was made according to the Rotterdam criteria: presence of anovulation/oligo-ovulation, signs of high androgen level (especially hirsutism), presence of polycystic ovary and/or increased ovarian size. PCOS was diagnosed when 2 of these 3 criteria were documented in patient and other conditions causing high testosterone level (like exogenous androgen administration, hyperprolactinemia, thyroid disorders, etc.) were excluded [12-13].
After including in study, demographic characteristics, weight, height, duration of infertility, duration of ovulation induction, total administered dose of FSH, IVF cycle parameters (number of retrieved and mature oocytes, mean size of follicles, number of embryos), rate of ovarian hyper-stimulation syndrome (OHSS) and clinical pregnancy rate were also derived and documented.
IVF success was defined as positive fetal heart rate in ultrasound scan 3-4 weeks after IVF. BMI was calculated as weight (kg)/height (m) 2. WHO standard classification of BMI was used for patient categorization: BMI of 18.5–24.9 kg/m2 was considered “normal”, BMI of 25–29.9 kg/m2 was considered as “overweight” and a BMI≥ 30 kg/m2 was considered “obese” [14].
Data Analysis
We used following formula to calculate the sample size of our study by considering the power of 90% and confidence interval of 95% with this hypothesis that the BMI impacts the outcome of IVF cycles in women with PCOS. Sample size was calculated as 176 but we included 200 cases to increase the strength of our results.

Descriptive data were reported as mean (±standard deviation), maximum and minimum. Categorical data were presented with percentages. Student’s t-test and Chi-Square test were used to compare the means. All analyses were done by SPSS statistical software SPSS, version 18 (SPSS, Inc., Chicago, IL).

200 cases were included and analyzed. Mean BMI of studied cases was 26.88(±6.55) with a minimum of 18 and maximum of 40.6. 72 patients had normal BMI (18.5-24.9), 85 cases were overweighed (BMI=25-30) and 43 cases were obese (BMI>30). Mean duration of infertility was 5.2 (±2.1) years in studied patients with a minimum of 2 and maximum of 15 years.  
IVF parameters- Duration of ovulation induction was statistically significant shorter in patients with normal BMI (P value=0.02). Number of retrieved oocytes was statistically significant higher in patients with BMI>30 but the number of mature oocytes and number of embryos were statistically lower in this group (table 2). Total dose of administered FSH, mean size of follicles and day of transfer were slimier in 3 studied groups (table 1).

Table1: Baseline data

IVF success rate- IVF was successful in 134 (67%) of cases. From 66 IVF failure cases, in 46(69.69%) cases beta-HCG was negative and in 20(30.30%) cases beta-HCG was positive but no fetal heart rate was detected in ultrasound scan. BMI had a statistically significant relationship with IVF success. Clinical pregnancy rate in obese patients was less than half of patients with normal or overweight BMI (p value=0.01). There was also a statistically significant relationship between age and IVF success (p value=0.034). success rate was about 43%  in patients younger than 35 years old and about 16% in patients older than 35 years old (table 2).

 Table2: IVF parameters and result in patients with different BMI

Effects of age- 133 women of 200 studied PCOS cases were younger than 35 years old. From these 133 cases, in 86(64.66%) IVF outcome was positive. 67 of 200 studied women were ≥35 years old. In 32 (48.5%) of these patients IVF outcome was positive. Positive IVF outcome was statistically significant higher in <35>

Figure1: Summary of Results

Table3: IVF parameters and result in patients under and above 35 years old