Impact of Body Mass Index (BMI) on Retrieval of Oocyte Numbers in In Vitro Fertilization Women

Abstract

Previous research and clinical reports have discovered that body weight significantly affects a patient’s fertility status. Underweight, overweight, or obese women may experience reduced fertility. Currently, assisted reproductive technology (ART) is used as treatment for infertile couples to conceive a child. However, whether abnormal body mass indexes (BMIs) affect infertile oocyte production is not clear. The objective of this study is to determine the association between BMI and retrieved oocyte numbers. A total of 136 IVF patient data in 2016 was reported from Reproductive Health Center. The relationship between patient’s BMI and retrieved oocyte numbers has been analyzed and their correlation coefficients between patients’ age, oocyte numbers, and BMI have been calculated. The results further proved that BMI affects collecting oocyte numbers and oocyte maturation rate. Overweight patients had fewer oocytes retrieved than that of normal weight patients. Likewise, obese patients had even fewer oocytes retrieved than that of both normal-weight and overweight patients. Underweight BMIs seem to have no effect on the number of oocytes collected; however, the oocyte quality and embryo production needs to be further studied. Results from this study may be used by IVF physicians and practitioners when consulting patients for IVF treatments.

1. Introduction

The impact of infertility causes significant mental and physical strain on both men and women. Numerous factors can influence male and female fertility. Common causes of female infertility may include anovulation, hormonal imbalances, structural issues or damage to fallopian tubes or uterus, cervical issues, decreased ovarian reserve with increased age, etc. In the past few decades, one rising factor affecting the fertility status is an individual’s body weight. Being severely underweight or overweight can disrupt the process of regular, consistent ovulation in females, leading to anovulation. In 2013, the American Society of Reproductive Medicine (ASRM) released “Optimizing Natural Fertility: A Committee Opinion” in which the society included recommendations on how to counsel patients to optimize the likelihood of becoming pregnant. ASRM reported that fertility rates are decreased in women who are underweight or obese based on body mass index (BMI).

According to the National Heart, Lung, and Blood Institute (NIH), the body mass index (BMI) is a standardized measure of an individual’s body fat percentage relative to their height and weight. A normal range is considered to be anywhere between 18.4 and 24.9, whereas an underweight value is below 18.4. Overweight values range from 25 to 29.9. Obese individuals have BMIs of 30 or greater. BMI can be calculated by an individual’s weight divided by their height squared (kg/m²). In relation to fertility, Hassan and Killick [1] reported that the time to conception was increased by more than twofold among overweight/obese women (BMI >25 kg/m²) and by more than fourfold among underweight women (BMI <19 kg/m²). With additional research suggesting the impact body weight has on one’s fertility status, the ASRM highlighted several points suggesting women who are obese to receive counseling prior to attempting to conceive in order to prevent potential medical, obstetric, or neonatal complications. In addition, the ASRM indicated that diet and exercise are the first-line treatments for obesity, where weight loss is linked to return of ovulation and decreased miscarriage rates in obese women who were previously infertile. Through pharmacotherapy, such as antiobesity medications, including orlistat, lorcaserin, naltrexone, may be used for obese women, it should only be considered for those who do not respond to a 6-month lifestyle modification. Furthermore, bariatric surgery may be considered to improve obesity-related issues regarding menstrual irregularity and infertility in women, however, pregnancy should not be considered within a year after surgery.

Based on the ASRM’s guidelines stated above, it is highly recommended for individuals who are severely underweight or overweight/obese to normalize their weight in order to improve their fertility status. Practitioners may provide patients with appropriate recommendations for weight loss/gain programs, nutritional counseling, dietary modifications, and/or exercise regimens. The goal of physicians should be to allow patients to be in their best possible health condition prior to starting any fertility treatments. This may be done to ensure lower complications of treatment, to better improve infertility treatment success, and to lower complications of pregnancy.

Currently, many infertility patients can be treated by assisted reproductive technologies (ART), in which fertilization of oocytes occurs in a laboratory environment. In vitro fertilization (IVF), the most common ART procedure, involves different stages for conception to occur, including oocyte retrieval from the ovaries, sperm introduction to oocytes, and successful transfer of embryo(s) back into the female for implantation. During the beginning of a cycle, follicle-stimulating hormone (FSH) injections are administered to patients during the follicular phase of the ovarian cycle to maximize the number of developing follicles. On days 12–14, a trigger shot, usually hCG (human chorionic gonadotropin), stimulates the final maturation of oocytes. Then, the matured oocytes are collected for fertilization in the laboratory. Once the oocyte is fertilized by the sperm to create a zygote, the embryo begins to divide. The embryo can be implanted in the uterus by day 3 or 5 after fertilization. Day 3 embryo cleavage comprises 6–9 cells that are in the process of dividing, but the embryo itself will not grow in size. Day 3 embryos can incubate further to day 5 blastocysts containing more advanced cellular structures. In situations where the quality of sperm is not optimal, intra-cytoplasmic sperm injection (ICSI) technique may be used to inject one sperm into the oocyte to increase the chances of successful fertilization.

A significant number of IVF and ICSI babies have been born throughout the world. However, a key factor of assisted reproductive techniques is the reliance on medicine and hormones to stimulate the ovaries to develop multiple follicles per cycle. Nonetheless, some patients may show less than optimal responses to the medication prescribed. One reason may be due to high and low BMIs. As a result, the number of retrieved oocytes, oocyte maturity, subsequent fertilization, embryo quality, and live birth rates may be reduced. Overweight women tend to have lower responses to medication to regulate and/or initiate ovulation, resulting in higher doses. In addition, women who are overweight/obese have a greater frequency of over-response and a higher risk of overstimulation. If a multiple pregnancy occurs, there are greater obstetrical complications in patients with higher BMIs than that of normal range BMIs. Additional complications include fewer eggs retrieved, increased difficulty during the retrieval process, increased risk of bleeding, increased risks of anesthesia, and greater difficulty during embryo transfer when visualizing the uterus.

Likewise, underweight individuals experiencing anorexia nervosa or bulimia are potentially at risk for infertility [2]. In patients who are malnourished or starving, a lowered metabolic rate, along with decreased gonadotropin release, may result in fertility loss. Deficiencies in estradiol, an important player in the female reproductive system that is commonly seen in anorexia is also due to low ovarian stimulation. As a result, patients who are underweight are advised to gain weight prior to starting fertility treatment.

Although previous studies have reported that being underweight or overweight/obese has significant effects on female fertility, there are no reports analyzing the effect of body weight on fertility factors, such as the number of oocytes retrieved and fertilized, embryo quality, and IVF outcomes. Therefore, this study is designed to examine the impact of body weight on fertility treatment outcomes. The goal of this study is to determine if fertility is impacted by individuals who are underweight, overweight, or obese by analyzing IVF outcomes so that practitioners may correctly counsel their patients before undergoing assisted reproductive technology.

2. Materials and methods

This was a retrospective study in an IVF laboratory. The deidentified data was collected from patients who have undergone IVF treatment in 2016 at the Reproductive Health Center in Tucson, Arizona. Information regarding patient IVF procedures includes: patient age, weight, height, number of retrieved oocytes, number of matured oocytes, number of embryos created, number of embryos transferred, pregnancy rates, and live birth.

Data for underweight and overweight patients were compared to individuals within the normal weight range. Body mass index (BMI) of each patient was calculated. The normal range is 18.4–24.9, whereas an underweight value is below 18.4. Overweight values range from 25 to 29.9. Obese values have BMIs of 30 or greater. BMI was calculated by an individual’s weight divided by their height squared (kg/m²). Using these ranges, the infertile patients were grouped into four categories (underweight, normal, overweight, and obese).

Prior to the procedure, various hormones, including gonadotrophin-releasing hormone/follicle-stimulating hormone (GnRH/FSH) injections (250-450IUs depending on patient age and BMI), were given to the patients to target the growth of follicles during an IVF cycle. Based on follicular size and blood estradiol level, at 36–37 hours after human chorionic gonadotrophin (hCG, 4000 to 10,000 IU) administration for oocyte maturation, the eggs were retrieved from ovaries through transvaginal by our physician standardized procedure. Therefore, the retrieved oocytes were classified as matured oocytes (MII), germinal vesicle (GV), postmatured oocytes, or degenerate oocytes. Only matured oocytes (MII) were used to calculate maturation percentage rate.

2.1 Statistical analysis

The average and standard deviation (means) of all data were calculated by Microsoft Excel. The significant differences between the averages were examined by student t-test statistical analysis, and the difference between the percentages was examined by percentage test method. The differences were considered statistically significant at p < 0.05.

3. Results

3.1 The effect of age on retrieval of oocyte numbers

Patient age was plotted as a function of oocyte number for 136 IVF egg retrieval patients, as shown in Figure 1.

Figure 1.

The correlation of patient’s age and collected oocyte numbers.

Figure 1 shows that the number of collected oocytes declines as a function of patient age. Greater number of oocytes were collected from younger patients than for older patients. The negative correlation demonstrates that as age increases, the number of retrieved oocytes is reduced. The correlation coefficient was calculated to be r = −0.66, which is also indicative of a negative correlation between patient age and oocyte numbers.

3.2 Relationship between age and BMI

There was no relationship between patient age and body mass index (Figure 2). The correlation coefficient is low (r = 0.11) and shows no statistical significance (p > 0.05). The averages of patient height, weight, BMI, and oocyte numbers in relationship to age ranges are represented in Table 1.

Figure 2.

A scatter diagram for relationship between patient age and body weight index (BMI).

Age (year old)	No. of patients	Height (in)	Weight (lbs)	BMI	Oocyte no.	Maturity
<25	35	64.4 ± 2.1	137.7 ± 14.3	23.4 ± 2.1	20.7 ± 8.3^a	77.3%
26–30	24	63.9 ± 2.3	146.5 ± 30.1	25.1 ± 4.8	18.7 ± 8.5^a	72.2%
31–35	42	65.5 ± 2.8	150.4 ± 21.2	24.6 ± 3.2	13.7 ± 5.6^b	81.7%
36–40	22	63.7 ± 1.5	140.8 ± 22.9	24.4 ± 3.9	8.6 ± 5.7^b	81.0%
>40	13	64.6 ± 2.5	153.2 ± 27.8	25.7 ± 4.0	12.3 ± 6.3^b	83.7%
Total	136	64.6 ± 2.4	145.2 ± 22.9	24.4 ± 3.6	15.6 ± 8.1	78.4%

Table 1.

Basic information from collected data in relation to BMI and oocyte numbers at different age ranges.

Note: letters a and b indicate significant difference (p < 0.05).

Table 1 shows that there was no significant difference in the patient’s height, weight, BMI, and oocyte maturity in various age ranges (p > 0.05). However, as age increases, the collected number of oocytes significantly decreased (p < 0.05).

3.3 Scatter diagram of patient body mass index and retrieval oocyte numbers

The number of eggs retrieved was plotted as a function of BMI (Figure 3). Most patients were in the normal body weight category (18.4–24.9 kg/m²). There were more overweight patients (24.9–29.9 kg/m²) and obese patients (>30 kg/m²) than underweight (<18.4 kg/m²) patients. The correlation coefficient between BMI and retrieved oocyte number was calculated to be r = −0.4177. The negative relationship indicates that as BMI increases, the number of oocytes collected decreased. The statistical test of correlation coefficient shows significant difference (P < 0.05).

Figure 3.

A scatter diagram of the relationship between body mass index and oocyte retrieval number.

3.4 The effect of patient’s BMI on retrieval of oocyte numbers

According to BMI classification, 136 patients undergoing IVF oocyte retrieval were divided into four groups: BMI < 18.4, BMI 18.5–24.9, BMI 25–29.9, and BMI > 30, representing underweight, normal weight, overweight and obese, respectively. Patient’s retrieval oocyte number and oocyte maturation rate have been analyzed (Table 2).

BMI	No. of patients	Height (in)	Weight (lb)	No. of retrieved oocytes	No. of matured oocytes	Oocyte maturation rate
<18.4	1*	64	100	20	16	80%
18.4–24.9	85	64.9 ± 2.5	134.6 ± 13.6^a	16.9 ± 8.5^a	13.2 ± 7.0^a	78.4%^a
25–29.9	40	63.8 ± 2.4	155.0 ± 15.3^b	13.75 ± 7.3^b	10.9 ± 5.8^b	79.7%^a
>30	10	65.1 ± 1.5	199.6 ± 12.3^c	11.6 ± 5.7^c	8.4 ± 4.9^c	72.4%^b
P value		P > 0.05	P < 0.05	P < 0.01	P < 0.05	P < 0.05
Total	136	64.6 ± 2.4	145.2 ± 22.9	15.6 ± 8.1	12.2 ± 6.7	77.6%

Table 2.

The relationship between patient BMI and number of retrieved oocytes.

Note: letters a, b and c indicate significant difference (p < 0.05). The star * shows only one patient with BMI <18.4 in collecting 136 patients. Although it does not have any statistical significance, it shows that this patient had enough of the number of retrieved oocytes and good maturity.

Based on Table 2, there is no significant difference in patient’s height, in different BMI groups, but as patient weight increases, the BMI shows an obvious big. The overweight patients (BMI 25–29.9) had significantly fewer retrieved oocytes than normal-weight patients. Similarly, obese patients (BMI >30) had significantly fewer retrieved oocytes than normal-weight and overweight patients (p < 0.01). Observing oocyte maturity, the number of matured oocytes in obese patients was significantly lower than that of normal-weight and overweight patients (p < 0.05). Thus, obese women had lower oocyte maturation rate. Figure 4 displays the number of retrieved oocytes and maturation rates in different BMI categories. This figure shows that as BMI increases, the numbers of retrieved oocytes and maturation rates are significantly reduced.

Figure 4.

Numbers of collection oocytes and maturation oocytes in various BMI patient groups. Note: Underweight group just had one patient with BMI <18.4.

4. Discussion

Infertility has affected more than 180 million people worldwide and has become an ongoing critical reproductive issue over recent decades [3]. Currently, the assisted reproductive technologies (ARTs) have been an effective measure to treat infertile couples in conceiving a child. However, the success of ART is closely associated with several demographic characteristics and physical conditions, including maternal age, female body mass index, potential diseases, lifestyle, and various environmental factors [4]. BMI has a significant effect on in vitro fertilization outcome in especially women. Women with overweight status and obesity status have been associated with higher infertility rates. In this study, we examined whether BMI affects retrieval of oocyte numbers and oocyte maturity. Our results showed that BMI significantly affected collection of oocyte numbers and its maturation rate. The overweight patients had significantly fewer oocyte numbers than that of normal weight patients. Similarly, obese patients had fewer oocyte numbers than normal-weight and overweight patients. Obese patients’ oocyte maturation rate was also much lower than normal and overweight patients. It has been suggested that obesity could have a detrimental effect on oocytes and endometrium [5] because obese women have a poor response to ovarian stimulation, and thereby need higher doses of gonadotropin hormone injections [6]. Thus, normal doses of medication injection for obese women may result in not enough matured oocytes retrieved.

However, according to the World Health Organization, being underweight is much less common with a prevalence of less than 5%, whereas having excess body weight constitutes around 50% of the adult population in developed societies [7]. As a result, fewer research and publication is generated on the negative impact of being underweight on spontaneous and assisted conception. The greatest concerns for underweight women in trying to conceive include the obstetric complications related to nutrition levels for the mother and fetus. This leads to increased risks of anemia, impaired weight gain, preterm delivery, low birth weight, postnatal complications, etc. In our collecting 136 patients, it is disappointing that there was only one patient in BMI < 18.4 group. Thus, we could do a statistical analysis for underweight group. We just listed this underweight Woman with a total of collected 20 oocytes and 16 matured oocytes. It is very difficult to be able to make conclusions regarding underweight patients and IVF treatment in this study.

The number of oocytes collected from women of different BMIs also depends on the age of the patient. We first analyzed the relationship between patient age and retrieved oocyte quantities. Similar to previous research [8], the number of oocytes retrieved and female age have a close association. This relationship represents a negative correlation coefficient (r = −0.66) between patient age and oocyte numbers, thereby indicating that the number of oocytes collected will significantly reduce as a patient is older. For example, although one patient with BMI < 18.4 in our study was underweight, her age was just 24 years old, and she might donate 20 oocytes and had 16 matured oocytes for IVF.

Also, our study indicated that there was no close relationship between age and BMI. The irregular dispersion of the scatter diagraph displays a low correlation coefficient (r = 0.11). Conversely, many reports have indicated a positive correlation between age and weight, where an increase in adult age is commonly associated with increased body weight and thus BMI. However, our results did not find any association between the two variables. This may be due to a limited age range of patients in the study. In other words, our study population may have limited generalizability because the infertile patients who have undergone IVF treatment ranged between 20 to 45 years old. Patients’ ages outside of this range were excluded from the analysis. Because of the limited age range, it is possible that weight gain is seen among women outside of this spectrum.

The original design of this study was aimed to analyze the effect BMI has on female IVF outcomes, which also included analyzing the quantity of embryo production and live birth. However, due to limitations of data quantity regarding these two variables, we were unable to analyze the numbers of embryo fertilization and live birth rates. Furthermore, embryo formation and patient pregnancy may be affected by numerous factors, including male sperm quality, female endometrium quality, prenatal complications, etc. Therefore, we concentrated on the association between female BMI and oocyte production and retrieval numbers. Results from this study may be a reflection of current infertile patient population who are seeking IVF treatment.

5. Conclusion

In summary, our study further verified that the quantity of oocyte retrieval and female age have a close association, where the age of a female significantly affects the number of oocytes that can be fertilized for artificial or natural conception. Thus, we further conclude that as age increases, the number of oocytes retrieved during an IVF treatment is significantly reduced. We did not find a close relationship between infertile female age and BMI; however, our results indicated that BMI has a strong influence on oocyte quantities and maturation rates. Overweight patients tended to have significantly fewer oocytes than that of normal weight patients. Likewise, obese patients have even fewer oocytes than that of normal-weight and overweight patients. Conversely, the underweight patient did not seem to have a difference in oocyte number and maturation rate, but we cannot conclude significant findings from this group since a greater sample size is required. Analysis of the study may be used by IVF physicians and practitioners to facilitate an optimal IVF treatment program for infertile patients seeking to conceive.

Acknowledgments

The author is sincerely grateful to Dr. Randi Weinstein for her ardent supervision, data collection, and editorial assistance during preparations of the thesis.