Document Type : Original Article
Authors
1 Department of Endocrinology and Female Infertility, Reproductive Biomedicine Research Centre, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran
2 Department of Endocrinology and Female Infertility, Reproductive Biomedicine Research Centre, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran;Department of Obstetrics and Gynaecology, Faculty of Medici
3 Department of Epidemiology and Reproductive Health, Reproductive Epidemiology Research Centre, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran
Abstract
Keywords
Obesity is an important risk factor for health problems
and is deemed to be 1 of the 10 global diseases that contributes
to an increased health burden. There is a rapidly
increasing incidence of this complication in many industrialized
countries, particularly the United States, and in
developing Asian countries (
In numerous studies, researchers evaluated the effects
of obesity on assisted reproductive technology (ART) cycle
outcomes in women (
Currently, there is no evidence to indicate that obesity
increases the risk for ART complications; however, some
researchers have reported the negative effects of obesity
on pregnancy rates (
The mechanism of the effects of female obesity on ART
outcomes is controversial. The impact of obesity on ART
outcomes in men is less studied (
This was a cross-sectional study performed at Royan Institute between January 2013 and January 2014. The Review Board and Ethics Committees of Royan Institute approved the study protocol. All participating couples provided ethical permission at their initial visit for the use of their treatment outcomes. Participant confidentiality for all participants was assured during the research and written informed consent was obtained from them.
We evaluated the data recorded during the study period
from all of the study participants. The study population
was limited to patients who underwent ICSI or IVF/ICSI
cycles that resulted in the transfer of 2 or 3 fresh embryos.
Height and weight were recorded for all couples. Couples
whose female partner was =39 years of age and the male
partner was <55 years of age (
Sampling procedure and the distribution of the couples according to their BMI. IVF; In vitro fertilization, ICSI; Intra-cytoplasmic sperm injection, BMI; Body-mass index, IUI; Intrauterine insemination, PGD; Pre-gestational diagnosis, TESE; Testicular sperm extraction, PESE; Percutaneous epididymal sperm extraction, PESA; Percutaneous epididymal sperm aspiration, and TESA; Testicular sperm aspiration.
The patients’ age (years) was recorded at the beginning
of treatment. At the onset of treatment, we classified
participants as smokers or non-smokers according
to the number of cigarettes smoked per day. The
diagnosis of infertility was determined according to
the 10th revision of the International Classification of
Diseases (
We defined normal fertilization as the appearance of
the 2nd polar body at 16-19 hours after insemination
or microinjection. In our institute, embryo quality is
graded as A, B, C, and D, with "A" defined as the best
quality and "D", the worst, according to cell numbers,
percentage of fragmentation, and cell symmetry. All
embryo transfers were performed with a Labotect catheter
(Labotect, Germany) by experienced gynaecologists
and embryologists on day 3 after IVF/ICSI. Luteal
phase support was provided by administration of 400
mg of vaginal progesterone twice a day until the day of
the ß-hCG test. Luteal support with progesterone was
prescribed until the observation of foetal heart activity
and subsequently tapered until week 8 of gestation. The
main outcomes were fertilization, implantation, clinical
pregnancy, and live birth rates. The implantation
rate was denoted as the number of visualized intrauterine
gestational sacs divided by the number of transferred
embryos. A clinical pregnancy was documented
by ultrasound observation of an intrauterine gestational
sac with foetal cardiac activity. We defined spontaneous
abortion as the loss of clinical pregnancy prior to
20 weeks gestation. Trained nurses routinely measured
height and weight in participants of both genders prior
to the onset of the treatment cycle. The balance scale
for the measurement of weight was calibrated daily
and verified by a one kg counterweight. We used the
World Health Organization’s definition of BMI (kg/m2)
to classify male and female participants as underweight
(<18.5 kg/m2), normal (18.5-24.9 kg/m2), overweight
(25-29.9 kg/m2), or obese (=30 kg/m2) (
Statistical analysis was carried out using the Statistical Package for the Social Sciences (SPSS), version 20.0 (SPSS Inc., Chicago, IL, USA). The study population’s characteristics were compared according to the couples’ BMI (normal, overweight, and obese) using one-way analysis of variance (ANOVA), Kruskal- Wallis nonparametric analysis of variance, and the chi-square test when appropriate. Multilevel logistic regression analysis was applied to determine the odds of live births following ICSI cycles. The analysis was conducted according to the female and male BMI groups. Normal-weight patients were considered to be the reference group. Analysis of female BMI was adjusted for age and duration of infertility. Likewise, analysis of the male BMI was adjusted for age, duration of infertility, and smoking status.
A multilevel logistic regression analysis was used to detect the predictive factors for live births after ICSI cycles. All possible factors that affected the live birth rate, which included female and male ages, couples’ BMI (<25 kg/m2 and =25 kg/m2), male smoking status, cause and duration of infertility, ovarian stimulation protocol [long gonadotropin-releasing hormone (GnRH) agonist and GnRH antagonist protocols], and number and quality of transferred embryos were incorporated into the model. The results of the multilevel logistic regression analysis have been presented as adjusted odds ratios (ORs) with 95% confidence intervals (CIs). P values <0.05 were considered statistically significant.
In total, there were 4203 ART cycles during the study
period. A total of 990 eligible women and their husbands
underwent 927 ICSI and 63 ICSI with insemination
(IVF/ICSI) cycles according to the inclusion
criteria. The sampling procedure and distribution of
the couples according to their BMI has been illustrated
in (
The characteristics of the study population according to
gender and BMI have been presented in (
Anovulatory cases in the present study consisted of participants with PCOS (n=153, 75%) and age factor (over 37 to 39 years, n=51, 25%).
Basic characteristics of the studied population according to gender and body mass index
Characteristics | Underweight | Normal weight | Overweight | Obese | P value | |
---|---|---|---|---|---|---|
n=59 | n=357 | n=412 | n=162 | |||
Women | ||||||
Age (Y) | 29.0 ± 3.9 | 30.0 ± 4.5 | 30.7 ± 4.8 | 32.2 ± 4.9 | <0.001 | |
Anovulatory cases | 11 (18.6) | 59 (16.5) | 84 (20.4) | 50 (30.9) | 0.003 | |
n=45 | n=297 | n=425 | n=223 | |||
Men | ||||||
Age (Y) | 35.1 ± 6.7 | 34.8 ± 5.6 | 35.0 ± 5.7 | 36.0 ± 6.4 | 0.081 | |
Smoking cases | 21 (35.5) | 58 (17.7) | 88 (21.3) | 69 (42.5) | 0.006 | |
Data are presented as mean ± SD or n (%).
We separately evaluated the impact of female and male
BMI on the live birth rate in ICSI. The results of the multilevel
regression analysis according to female and male
BMI has been shown in (
The comparison of the three groups of couples according
to BMI has been demonstrated in (
Multilevel logistic regression analyses of the probability for live births following all ICSI or IVF/ICSI cycles according to gender and stratified by BMI
Variables | n (%) | ORa | 95% CI | P valueb | |
---|---|---|---|---|---|
Femaleb BMI, (n=990 ICSI cycles among 990 women) | |||||
Ovulatory | |||||
Underweight | 48 (6.1) | 6.5 | (2.1-20.65) | 0.001 | |
Normal weight | 298 (37.9) | Reference group | - | - | |
Overweight | 328 (41.0) | 0.30 | (0.11-0.83) | 0.021 | |
Obese | 112 (14.2) | 0.14 | (0.02-0.99) | 0.049 | |
Trend | 786 (100) | 0.91 | (0.83-0.99) | 0.045 | |
Anovulatory | |||||
Underweight | 11 (5.3) | 7.30 | (0.99-55.1) | 0.050 | |
Normal weight | 59 (28.9) | Reference group | - | - | |
Overweight | 84 (41.1) | 0.50 | (0.10-2.4) | 0.392 | |
Obese | 50 (24.5) | 0.14 | (0.009-2.4) | 0.186 | |
Trend | 204 (100) | 0.85 | (0.72-0.98) | 0.021 | |
Maleb BMI, (n=990 ICSI cycles among 990 men) | |||||
Underweight | 45 (4.5) | 0.295 | (0.02-3.96) | 0.352 | |
Normal weight | 297 (30.0) | Reference group | - | - | |
Overweight | 425 (42.9) | 0.07 | (0.0-10.71) | 0.360 | |
Obese | 223 (22.5) | 0.012 | (0.0-21.89) | 0.294 | |
Trend | 990 (100) | 1.01 | (0.95-1.09) | 0.647 | |
OR; Odds ratio, CI: Confidence interval, BMI; body mass index, IVF; In vitro fertilization, ICSI; Intra-cytoplasmic sperm injection, a; ORs with 95% CIs and P values from Wald tests, and b; Female analyses adjusted for age and duration of infertility. Male analyses adjusted for age, duration of infertility, and smoking status.
Comparison of study population characteristics and cycle outcomes among three groups of couples according to BMI
Variable | Normal weight couplesn=126 | Overweight couplesn=177 | Obese couples n=45 | Test | P | |
---|---|---|---|---|---|---|
Female age (Y) | 30.0 ± 4.7 | 30.5 ± 4.6 | 32.3 ± 4.7 | ANOVA | 0.018ᵃ | |
Male age (Y) | 33.4 ± 4.7 | 35.1 ± 5.9 | 37.9 ± 5.4 | ANOVA | <0.001ᵇ | |
Female FSH (IU/l) | 6.8 ± 3.6 | 6.1 ± 3.0 | 6.9 ± 3.4 | ANOVA | 0.160 | |
Female LH (IU/l) | 4.7 ± 3.3 | 4.6 ± 4.1 | 4.6 ± 4.7 | ANOVA | 0.986 | |
Female AMH (ng/ml) | 2.3 ± 1.7 | 2.4 ± 1.6 | 2.0 ± 1.4 | Kruskal-Wallis | 0.646 | |
Female TSH (mIU/l) | 2.1 ± 1.8 | 2.3 ± 1.9 | 2.3 ± 1.7 | ANOVA | 0.658 | |
Type of infertility | Chi-square | 0.426 | ||||
Primary | 107 (84.9) | 157 (88.7) | 37 (82.3) | |||
Secondary | 19 (15.1) | 20 (11.3) | 8 (17.7) | |||
Cause of infertility | Chi-square | 0.150 | ||||
Ovulatory | 105 (83.3) | 32 (71.1) | 147 (83.1) | |||
Anovulatory | 21 (16.7) | 13 (28.9) | 30 (16.9) | |||
Male factor infertility cases | 89 (70.6) | 30 (66.7) | 131 (74) | Chi-square | 0.577 | |
Infertility duration (Y) | 5.1 ± 3.4 | 6.39 ± 4.7 | 7.08 ± 4.7 | ANOVA | 0.011c | |
Number of previous ART cycles | 0.4 ± 0.9 | 0.3 ± 0.6 | 0.4 ± 0.9 | ANOVA | 0.583 | |
Stimulation duration (days) | 10.7 ± 2.0 | 10.6 ± 2.1 | 10.9 ± 2.4 | ANOVA | 0.664 | |
Total amount of rFSH dose (IU) | 1932.6 ± 724.0 | 1810.1 ± 821.8 | 1839.9 ± 844.4 | Kruskal-Wallis | 0.176 | |
Total dose of used gonadotropins (IU) | 2086.1 ± 1005.4 | 2087.9 ± 903.8 | 2251.6 ± 1206.3 | ANOVA | 0.582 | |
Stimulation protocol | Chi-square | 0.564 | ||||
Long agonist | 108 (85.7) | 40 (88.9) | 149 (84.2) | |||
Antagonist | 18 (14.3) | 5 (11.1) | 28 (15.8) | |||
Total number of retrieved oocytes | 8.9 ± 4.3 | 8.3 ± 3.4 | 8.0 ± 3.52 | ANOVA | 0.327 | |
Total number of embryos | 5.1 ± 2.7 | 5.0 ± 2.7 | 5.0 ± 2.50 | ANOVA | 0.974 | |
Number of transferred embryo | 2.4 ± 0.56 | 2.4 ± 0.5 | 2.4 ± 0.55 | ANOVA | 0.978 | |
Endometrial thickness on transfer day (mm) | 9.9 ± 1.4 | 9.9 ± 1.6 | 9.5 ± 1.9 | ANOVA | 0.293 | |
Quality of transferred embryos (ET)* | Chi-square | 0.675 | ||||
Good | 82 (65.1) | 111 (62.7) | 32 (71.1) | |||
Fair | 11 (8.7) | 20 (11.3) | 2 (4.4) | |||
Poor | 33 (26.2) | 46 (26) | 11 (24.4) | |||
Fertilization rate | 0.74 ± 0.23 | 0.73 ± 0.24 | 0.78 ± 0.21 | ANOVA | 0.523 | |
Implantation rate | 0.28 ± 0.173 | 0.31 ± 0.2 | 0.33 ± 0.16 | ANOVA | 0.593 | |
Clinical pregnancy rate | 40 (78.4) | 68 (89.5) | 21 (87.5) | Chi-square | 0.407 | |
Blighted ovum | 9 (17.6) | 6 (7.9) | 2 (8.3) | Chi-square | 0.231 | |
Ectopic pregnancy rate | 2 (3.9) | 2 (2.6) | 1 (4.2) | Chi-square | 0.936 | |
Multiple pregnancy rate | 7 (19.4) | 15 (27.3) | 5 (27.8) | Chi-square | 0.664 | |
Miscarriage rate | 2 (5.3) | 9 (14.1) | 2 (10) | Chi-square | 0.362 | |
Live birth rate | 36 (94.7) | 55 (85.9) | 18 (90) | Chi-square | 0.345 | |
Data are presented as mean ± SD or n (%). BMI; Body mass index, FSH; Follicle stimulating hormone, LH; Luteinizing hormone, AMH; Anti-Müllerian hormone, TSH; Thyroid stimulating hormone, ART; Assisted reproductive technology, rFSH; Recombinant follicle-stimulating hormone, ANOVA: One-way analysis of variance, a; Obese couples vs. overweight couples (P=0.015), normal BMI vs. obese couples (P=0.040) according to Tukey’s test, b; Normal BMI vs. overweight couples (P=0.013), normal BMI vs. obese couples (P<0.001), overweight vs. obese couples (P=0.086) according to Tukey’s test, c; Normal BMI vs. overweight couples (P=0.032), normal BMI vs. obese couples (P=0.021) according to Tukey’s test, *; Good quality embryos-all ET were A, B, or AB, Fair-half of ET were good quality (AC, BC), Poor quality-all ET were C, D, or CD.
The results of the multilevel logistic regression model for the detection of the predictive factors for the live birth rate showed that none of the included variables remained in the final model as significant factors. The results also revealed no significant association between the couples’ BMI and live births (
Multilevel logistic regression analysis for detection of predictive factors for live birth after ICSI or IVF/ICSI cycles in the studied population
Combined BMI (kg/m2) | Live birth per ICSI cycle | ||||
---|---|---|---|---|---|
Women | Men | n (%) | OR | 95% CI | P value |
<25 | <25 | 161 (16.3) | 1 | Reference group | - |
<25 | ≥25 | 255 (25.8) | 1.03 | 0.5-1.9 | 0.914 |
≥25 | <25 | 181 (18.3) | 0.6 | 0.3-1.2 | 0.262 |
≥25 | ≥25 | 393 (39.7) | 0.8 | 0.4-1.9 | 0.864 |
ICSI; Intracytoplasmic sperm injection, IVF; In vitro fertilization, BMI; Body mass index, OR; Odds ratio, and CI; Confidence interval.
Previous studies separately evaluated the effects of both
genders’ BMI on ART outcomes. The synergistic effects
of obesity in couples were reported in limited studies (
Our results supported those published in 2013 by Petersen
et al. (
The effects of female BMI on ART outcomes were evaluated
in several studies. Our findings showed that among
ovulatory women, BMI had a negative impact on live
births. In anovulatory women, we observed a tendency
for less odds of live births in the obese group, which was
not statistically significant. Therefore, our results agreed
with some recent studies where female BMI negatively
impacted ART outcomes (
The influence of male BMI on ART outcomes has been
less studied. The existing literature contains only 7 studies
on this subject (
We analysed the couples and found no synergistic negative
impact of increased female and male BMI on live
births after ICSI cycles. This finding agreed with studies
by Petersen et al. (
The present study has some limitations. There was no data about the specific hormonal profile and android or gynoid distribution of fat in anovulatory and ovulatory women, and no data about semen analysis parameters to compare among different BMI groups. We propose that these parameters should be considered in future studies.
Based on the current findings, an increased maternal BMI independently influenced negatively live birth rate after ICSI cycles, whereas increased paternal BMI separately and in combination with maternal BMI did not show this affect.