Abstract
Background
Obesity is a highly prevalent chronic disease with a significant and complex impact on reproduction. National guidelines recommend weight loss prior to pregnancy for patients with obesity to mitigate complications and increase fertility; however, targeted, personalized interventions are limited. The objectives of this study are to describe the implementation of a multidisciplinary program designed specifically for women with reproductive disorders and obesity and to report differences in baseline characteristics and weight loss outcomes between women willing vs. not willing to defer pregnancy attempts to focus on weight loss.
Methods
Retrospective cohort study at a university multidisciplinary program for women with reproductive disorders and obesity. All participants from program initiation (November 2021) through July 2023 were included in the analysis. Primary outcome was percent body weight loss at 3 months. Secondary outcomes included weight loss at 6 months and achievement of > 5% and > 10% weight loss at each time point.
Results
A total of 237 participants were included in the analysis. The majority of participants (88.2%) desired pregnancy. 63.2% of participants who desired pregnancy were willing to postpone pregnancy attempts/fertility treatments so that they could focus on weight loss for at least 3 months. Participants willing to defer pregnancy attempts achieved a significantly greater weight loss at 3 months compared to those who continued pregnancy attempts (mean − 4.8% vs. -2.5%, p = 0.004) and were more likely to achieve > 10% body weight loss at 3 months (14.0% vs. 2.20%, p = 0.031). Those who achieved > 5% weight loss by 6 months were more likely to achieve pregnancy within the first 6 months of trying to conceive (34.1% vs. 7.7%, p = 0.004).
Conclusions
We describe the development and implementation of a multidisciplinary program for women with reproductive disorders and obesity seeking weight management. An individualized approach to weight management and reproductive care results in clinically significant weight loss especially among women willing to defer pregnancy attempts and focus on weight loss for at least 3 months.
Trial registration
Clinical trial number: Not applicable.
Supplementary Information
The online version contains supplementary material available at 10.1186/s12958-025-01415-x.
Keywords: Weight loss, Obesity, Infertility, PCOS, Anti-obesity medication, Weight navigation, Reproduction
Background
Obesity is a highly prevalent chronic disease, affecting over 40% of US adults [1]. While men and women experience similar overall rates of obesity (defined as a BMI ≥ 30 kg/m²), the rate of severe obesity (BMI ≥ 40 kg/m²) is nearly double in women compared with men (12.1% vs. 6.7%) [1]. Obesity affects nearly one-third of reproductive-aged women before pregnancy [2].
The impact of obesity on reproduction is both significant and complex. Clinically, women with obesity often experience menstrual irregularities, anovulation, and longer time to pregnancy [3–8]. Infertility rates are higher in women with obesity, and fertility treatments are less successful [3, 9–11]. During pregnancy, obesity is also associated with an increased risk of miscarriage, hypertensive disorders of pregnancy, gestational diabetes, cesarean section, and stillbirth [12]. Given the impact of obesity on fertility as well as associated maternal and fetal risks, national societies recommend weight loss for women with obesity prior to pregnancy [12]. Despite broad recommendations for weight loss, interventions to achieve this goal are usually limited to encouragement of general behavioral modification and/or referral to comprehensive weight management programs [12], rather than treatments designed specifically for this unique and underrepresented population. Furthermore, long wait times for specialty clinics may pose challenges for women of advanced reproductive age who wish to conceive [13].
In addition to a lack of personalized interventions, women with obesity and reproductive disorders may face significant barriers to receiving comprehensive and sensitive care. Individuals with obesity face pervasive society-wide stigma which adversely affects the quality of healthcare provided [14, 15]. Fear of judgment along with internalized weight bias may also result in delay of care with studies demonstrating a direct correlation between an increase in body weight and subsequent delay or avoidance of healthcare [16, 17]. Thus, many women with obesity may struggle to even present for care and upon presentation they may face additional barriers such as BMI restrictions for fertility treatment [18, 19]. These obstacles create a major gap in clinical care where women are instructed to lose weight or are denied reproductive care entirely until a specific BMI is achieved, yet they are often not provided with concrete guidance and support to achieve the recommended weight loss.
To fill this gap, we report the development of a multidisciplinary weight management program aimed at providing comprehensive weight loss counselling and obesity treatment that also considers reproductive and gynecologic history, reproductive age, family building goals, and obstetrical risks. The overall objectives of this study are to (1) describe the design and implementation of a multidisciplinary program for women with reproductive disorders and obesity (2) report baseline characteristics, treatment selection, and weight loss outcomes of participants and (3) understand differences in baseline characteristics and weight loss outcomes between women who were willing vs. not willing to defer pregnancy attempts to focus on weight loss.
Methods
Program design
The Michigan Interdisciplinary Clinic for Obesity and Reproduction (MICOR) is designed specifically for women interested in current or future pregnancy who also have a reproductive disorder such as infertility, Polycystic Ovary Syndrome (PCOS), endometriosis, or abnormal uterine bleeding. The MICOR program incorporates a unique model of weight management among reproductive-aged women by providing weight management counseling and individualized weight loss plans as well as comprehensive counselling regarding current obstetrical and reproductive risks while also considering ideal family size, age and fertility status. MICOR patients work with a multidisciplinary team including a nutritionist, social worker, and physicians specializing in Maternal Fetal Medicine (MFM), Obesity Medicine (American Board of Obesity Medicine (ABOM) diplomate) and REI (also ABOM diplomate). Specialty providers meet with patients in one-on-one sessions through virtual care to improve access and efficiency of time management. Prior to the start of the session, the multidisciplinary team meets to discuss each patient, an approach which allows the patients to leave with a personalized weight loss plan that factors in reproductive goals. Individualized weight loss plans are developed utilizing all university weight loss resources and modelled after the Weight Navigation Program [20]. The Weight Navigation Program utilizes American Board of Obesity Medicine-certified primary care physicians to provide weight-focused visits and guide weight management treatments based off patient preference. Weight navigation includes a discussion of available weight management options throughout the university including individualized nutrition plans and registered dietician support, a supervised very low-calorie meal-replacement program, bariatric surgery, endoscopic bariatric therapy, and incorporation of anti-obesity medications (AOMs). MICOR expands on this model by also incorporating reproductive and obstetrical assessment and risk counseling. Specifically, weight loss plans consider family building, age, ovarian reserve, and current/future plans for fertility treatments. MFM obstetrical preconception counseling includes evaluation of current medical co-morbidities and medications, risks during pregnancy, the need for additional testing and evaluation prior to pregnancy, counseling on physical activity recommendations (prior to and during pregnancy), and weight gain recommendations during pregnancy. During their encounter with REI, participants discuss planned fertility treatments and/or pregnancy attempts as well as the risk/benefits of delaying conception for more focused weight management. Patient-specific reproductive disorders such as PCOS, obesity-related anovulation, and infertility are reviewed in detail and the benefits of weight reduction (while also considering the impact of age and ovarian reserve status) are discussed. As most weight loss options (except for a more general pregnancy-safe nutrition plan) require avoidance of pregnancy, contraception is also discussed as appropriate for selected treatment option. Social work visits assess current mental health, provide resources and support, and consider how prior experiences with external and internalized stigma/bias may influence motivation and weight management. Following initial consultation with the entire team and selection of a weight management plan, individuals follow longitudinally with REI, social work, and nutrition (unless directly referred into a meal replacement program or bariatric surgery). Future visits assess weight loss, pharmacotherapy adjustment, and pregnancy planning.
Study design
This was a retrospective cohort study of all patients who presented to the Michigan Interdisciplinary Clinic for Obesity and Reproduction between November 2021 (clinic establishment) and July 2023. Data was abstracted from the electronic medical record by chart review from every completed MICOR visit during the study period. Demographic and clinical data, including past medical history, weight management selection, weight loss, and pregnancy outcomes, was abstracted. Information on utilization of anti-obesity medications (AOMs) was also collected including use of any of the following FDA approved medications: Liraglutide, Semaglutide, Tirzepatide, Phentermine with or without Topiramate ER, and Naltrexone/Bupropion. Individuals were further characterized based on their willingness to delay pregnancy and/or fertility treatments to focus on weight management. The primary outcome of the study was percent body weight loss at 3 months. Secondary outcomes included weight loss at 6 months and achievement of > 5% and > 10% weight loss at each time point.
Ethical approval of this study was granted by the University of Michigan Institutional Review Board (HUM00227298). Informed consent was waived as this is a retrospective review of existing data included in the standard care of patients.
Data analysis
Baseline descriptive statistics were assessed via calculation of means, medians and proportions as appropriate. Comparisons between continuous variables were analyzed using a Kruskal-Wallis test as normality assumptions were not met; categorical variables were compared with chi-squared tests; ordinal categorical variables were compared with a Mantel-Haenszel chi-squared test. Bonferonni correction was performed in subgroup analyses as appropriate. Power calculations for comparison of baseline characteristics and medical history between those individuals desiring pregnancy who were not willing vs. willing to defer pregnancy attempts demonstrated power values between 65 and 89%. For comparison of individuals who did vs. did not achieve > 5% total body weight loss at 6 months, power values were between 63 and 98%. Linear and logistic regression were also performed to assess for predictors of overall weight loss and > 5% weight loss respectively.
Results
A total of 237 patients were seen in MICOR between November 2021 and July 2023 and included in the analysis. Follow-up data was available on 167 individuals at 3 months and 80 individuals at 6 months. Baseline characteristics and medical history of all individuals who participated in MICOR are shown in Table 1. The mean age was 32.9 ± 5.5 years and mean BMI was 43.5 ± 7.3 kg/m2. Upon presentation to the clinic, 64.6% of patients had at least one metabolic co-morbidity, such as hypertension (16.9%), hyperlipidemia (31.6%), pre-diabetes (Hemoglobin A1C between 5.7 and 6.4%) (29.5%), or diabetes mellitus (14.8%). In terms of obstetrical and gynecologic history, 51.9% of individuals reported a prior pregnancy, while about half of those individuals (26.6%) reported a prior live birth (Table 1). 61.6% had a diagnosis of infertility, and 51.9% had a diagnosis of PCOS at time of presentation. The majority of participants (88.2%) desired pregnancy at time of their first MICOR visit. Differences in baseline characteristics and medical history between those not interested vs. interested in pregnancy are shown in Supplemental Table 1. Those who presented to MICOR and were not interested in pregnancy had a lower starting BMI (40.6 ± 7.69 vs. 43.8 ± 7.23, p = 0.030), were more likely to identify as Black or African American (50.0% vs. 23.4%, p = 0.040), were more likely to have a history of fibroids (28.6% vs. 9.6%, p = 0.003) and were less likely to have a history of infertility (0% vs. 69.9%, p < 0.001).
Table 1.
Baseline characteristics and medical history of all individuals participating in MICOR
| All participants | n = 237 |
|---|---|
| Age (years) - mean ± SD, [CI] | 32.9 ± 5.54, [32.2–33.6] |
| BMI (kg/m2) - mean ± SD, [CI] | 43.5 ± 7.34, [42.5–44.4] |
| Race n (%) | |
| Asian American (Chinese, Indian, Japanese, Korean, etc.) | 9 (3.8%) |
| Black or African American | 63 (26.6%) |
| Native Hawaiian or Other Pacific Islander | 1 (0.4%) |
| White/Caucasian | 149 (62.9%) |
| Other | 14 (5.9%) |
| Ethnicity n (%) | |
| Hispanic/Latino/Latina/Latinx | 20 (8.4%) |
| Non-Hispanic/Non-Latino | 214 (90.3%) |
| Medical History | |
| Diabetes Mellitus n (%) | 35 (14.8%) |
| Pre-Diabetes Mellitus n (%) | 70 (29.5%) |
| Hypertension n (%) | 40 (16.9%) |
| Hyperlipidemia n (%) | 75 (31.6%) |
| At least 1 metabolic co-morbidity n (%) | 153 (64.6%) |
| At least 2 metabolic co-morbidities n (%) | 59 (24.9%) |
| Depression n (%) | 66 (27.8%) |
| Anxiety n (%) | 66 (27.8%) |
| Obstetric and Gynecologic History | |
| Prior Pregnancy n (%) | 123 (51.9%) |
| Prior Live Birth n (%) | 63 (26.6%) |
| Currently Desires Pregnancy n (%) | 209 (88.2%) |
| History of Infertility n (%) | 146 (61.6%) |
| History of PCOS n (%) | 123 (51.9%) |
| History of Fibroids n (%) | 28 (11.8%) |
| AMH (ng/mL) - mean ± SD, [CI] | 4.18 ± 3.708, [3.63–4.73] |
Following initial counselling with the multidisciplinary team and discussion of available weight management options, participants selected a treatment plan based on shared decision making. Figure 1 demonstrates initial treatment selection. The majority of participants (86.4%) elected to work with the MICOR dietician, while 45.6% were also started on an anti-obesity medication (AOM) in conjunction with nutritional support. Selection of a specific pharmacotherapy was based on anticipated break from pregnancy attempts, medical contraindications, and insurance coverage. 7.2% of participants elected to enroll in a supervised very low-calorie meal replacement program run through the Michigan Metabolism, Endocrinology & Diabetes division. A small percentage of individuals (3.4%) elected for a referral to bariatric surgery.
Fig. 1.
Weight management treatment selected at time of initial MICOR visit. Bar graph demonstrating percentage of patients selecting a particular weight management treatment
To understand patient motivation and decision making, participants were next analyzed by their willingness to defer pregnancy for at least 3 months to focus on weight loss. Differences in baseline characteristic and medical history are demonstrated in Table 2. A total of 209 participants desired pregnancy at time of presentation. 132 of those individuals (63.2%) were willing to postpone pregnancy attempts/fertility treatments to focus on weight loss. Participants willing to defer pregnancy attempts were less likely to have a diagnosis of Diabetes Mellitus (10.6% willing to defer pregnancy vs. 22.1% not willing to defer pregnancy, p = 0.024) and anxiety (20.5% willing to defer pregnancy vs. 36.4% not willing to defer pregnancy, p = 0.012). There were no statistically significant differences in age, BMI, race, or presence of other medical co-morbidities. In terms of obstetric and gynecologic history, Anti-Mullerian Hormone (AMH) was higher in the group willing to defer pregnancy (mean 4.80ng/mL willing to defer pregnancy vs. mean 3.24ng/mL not willing to defer pregnancy, p = 0.004). There were no other differences noted between groups, including prior pregnancy history or current diagnosis of infertility or PCOS.
Table 2.
Differences in baseline characteristics and medical history between those individuals desiring pregnancy who are not willing vs. willing to defer pregnancy attempts
| All participants (n = 209) |
No (n = 77) |
Yes (n = 132) |
p-value1 | |
|---|---|---|---|---|
| Age (years) - mean ± SD, CI | 33.0 ± 5.27 | 33.2 ± 5.85, [31.9–34.5] | 32.9 ± 4.92, [32.0-33.7 | 0.793 |
| BMI (kg/m2) - mean ± SD, CI | 43.8 ± 7.23 | 43.5 ± 7.64, [41.8–45.3] | 44.0 ± 7.01, [42.8–45.2] | 0.667 |
| Race n (%) | 0.162 | |||
| Asian American (Chinese, Indian, Japanese, Korean, etc.) | 7 (3.3%) | 1 (1.3%) | 6 (4.5%) | |
| Black or African American | 49 (23.4%) | 19 (24.7%) | 30 (22.7%) | |
| Native Hawaiian or Other Pacific Islander | 1 (0.5%) | 1 (1.3%) | 0 (0.0%) | |
| White/Caucasian | 137 (65.6%) | 47 (61.0%) | 90 (68.2%) | |
| Other | 14 (6.7%) | 8 (10.4%) | 6 (4.5%) | |
| Ethnicity n (%) | 0.884 | |||
| Hispanic/Latino/Latina/Latinx | 18 (8.6%) | 6 (7.8%) | 12 (9.1%) | |
| Non-Hispanic/Non-Latino | 189 (90.4%) | 70 (90.9%) | 119 (90.2%) | |
| Medical History | ||||
| Diabetes Mellitus n (%) | 31 (14.8%) | 17 (22.1%) | 14 (10.6%) | 0.024 |
| Pre-Diabetes Mellitus n (%) | 62 (29.7%) | 18 (23.4%) | 44 (33.3%) | 0.128 |
| Hypertension n (%) | 37 (17.7%) | 11 (14.3%) | 26 (19.7%) | 0.323 |
| Hyperlipidemia n (%) | 64 (30.6%) | 20 (26.0%) | 44 (33.3%) | 0.266 |
| At least 1 metabolic co-morbidity n (%) | 134 (64.1%) | 48 (62.3%) | 86 (65.2%) | 0.682 |
| At least 2 metabolic co-morbidities n (%) | 53 (25.4%) | 17 (22.1%) | 36 (27.3%) | 0.405 |
| Depression n (%) | 58 (27.8%) | 26 (33.8%) | 32 (24.2%) | 0.138 |
| Anxiety n (%) | 55 (26.3%) | 28 (36.4%) | 27 (20.5%) | 0.012 |
| Obstetric and Gynecologic History | ||||
| Prior Pregnancy n (%) | 113 (54.1%) | 48 (62.3%) | 65 (49.2%) | 0.067 |
| Prior Live Birth n (%) | 58 (27.8%) | 26 (33.8%) | 32 (24.2%) | 0.138 |
| History of Infertility n (%) | 146 (69.9%) | 52 (67.5%) | 94 (71.2%) | 0.576 |
| History of PCOS n (%) | 108 (51.7%) | 36 (46.8%) | 72 (54.5%) | 0.277 |
| History of Fibroids n (%) | 20 (9.6%) | 10 (13.0%) | 10 (7.6%) | 0.200 |
| AMH (ng/mL) - mean ± SD, CI | 4.18 ± 3.725 | 3.24 ± 3.056, [2.46–4.01] | 4.80 ± 3.999, [3.98–5.61] | 0.004 |
1Continuous variables use a Kruskal-Wallis test for comparison; categorical variables use a chi-squared test for comparison; ordinal categorical variables use a Mantel-Haenszel chi-squared test for comparison
Participants willing to defer pregnancy attempts achieved a significantly greater weight loss at 3 months compared to those who continued pregnancy attempts (mean − 4.8% vs. -2.5%, p = 0.004) (Fig. 2A). Individuals willing to defer pregnancy were also more likely to achieve > 10% body weight loss at 3 months (14.0% vs. 2.20%, p = 0.031) (Fig. 2B). At 6 months those willing to defer pregnancy similarly demonstrated a greater mean weight loss (-6.5% vs. -2.6%, p = 0.02) and were significantly more likely to have achieved > 5% weight loss (61.4 vs. 28.6%, p = 0.024) (Fig. 2C &D).
Fig. 2.
Differences in weight loss at 3 and 6 months between those willing vs not willing to delay pregnancy attempts. A) Dot plot demonstrating mean weight loss at 3 months, lines represent 95% confidence intervals. B) Bar graph demonstrating the percentage of individuals achieving >5% and >10% weight loss at 3 months. C) Dot plot demonstrating mean weight loss at 6 months, lines represent 95% confidence intervals. D) Bar graph demonstrating the percentage of individuals achieving >5% and >10% weight loss at 6 months.
To evaluate for participant characteristics associated with successful weight loss, we next evaluated MICOR participants at 3 months and 6 months who achieved > 5% weight loss, and assessed for differences in baseline characteristics, medical, and gynecologic history (Supplemental Tables 2 &3). There were no differences found between those who did vs. did not achieve > 5% weight loss at 3 months (Supplemental Table 2). At 6 months we found that those who identified as White/Caucasian were more likely to achieve > 5% loss (p = 0.028) as were those patients who had hyperlipidemia at baseline (p = 0.022). Patients with Diabetes Mellitus were less likely to achieve > 5% weight loss at 6 months (p = 0.024). Logistic and linear regression were also performed to try and identify predictors of weight loss success, with willingness to delay pregnancy identified as the only predictor of achieving > 5% body weight loss at 6 months (OR 18.44 95%CI [1.3–256.0]).
To try to understand how weight loss may impact fertility/pregnancy outcomes in this population, pregnancy (within the first 6 months of attempted conception) and miscarriage rates were also evaluated. Pregnancy rates were calculated for all individuals attempting conception, regardless of type of fertility treatment. A total of 31 participants achieved pregnancy during the study. Those individuals who elected to defer pregnancy to focus on weight loss were less likely to conceive within the first 6 months (23.5% vs. 37.7%, p = 0.029), however, there was no difference in miscarriage rate between the 2 groups (24.1% vs. 32.3%, p = 0.485). To further assess how successful weight may impact conception, pregnancy rates were then compared between individuals who achieved > 5% weight loss vs. those who did not achieve 5% weight loss (Supplemental Tables 2 &3). There were no differences seen in pregnancy rates or miscarriage rates among those who achieved > 5% vs. those who did not achieve > 5% weight loss at 3 months (Supplemental Table 2). However, those participants who achieved > 5% weight loss at 6 months were more likely to achieve pregnancy within the first 6 months of trying to conceive (34.1% vs. 7.7%, p = 0.004), and achieve any conception (including beyond initial 6 months of attempted conception) (56.1% vs. 15.4%, p < 0.001) when compared to those who did not achieve > 5% weight loss (Supplemental Table 2). There was no difference in miscarriage rates (7.7% vs. 14.6%, p = 0.326).
Discussion
Here we report the successful establishment of a multidisciplinary weight management program for women with reproductive disorders and obesity. We found that when offered personalized weight management strategies, many women (63.2%) elected to postpone pregnancy/fertility treatments for at least 3 months to focus on weight management and ultimately achieved greater weight loss than those women not deferring pregnancy attempts.
Weight loss strategies were diverse and tailored per patient preference. This is important as recent data suggests that personalized diet and activity treatments may be more effective in achieving weight loss compared to standard recommendations [21]. Among all patients seen in MICOR (including those not desiring pregnancy), we found that most women elected to proceed with nutritional interventions (86.4%). Nutritional plans were created by a registered dietician with macronutrient and calorie recommendations based on whether a patient was actively trying to conceive. Among those women trying to conceive, a gentle low carbohydrate plan was usually suggested (approximately 100-130gm of carbohydrates per day with a focus on weight-based protein intake) [22]. For individuals who were not actively attempting pregnancy, nutritional plans included low carbohydrate (50-130gm carbohydrate per day), very low carbohydrate interventions (< 50gm of carbohydrate per day), and low-calorie interventions (generally 1200-1500 kcal per day) [22, 23]. Individuals interested in very low-calorie options were directly referred into a supervised meal-replacement program managed by the department of endocrinology which incorporates meal replacements and targets 800 kcal per day [24].
Anti-obesity medications (AOMs) were utilized in 45.6% of individuals. It is notable that in the general US population, AOMs are severely underutilized with only 1–3% of eligible patients with obesity receiving prescriptions [25, 26]. There are several short and long-term medications currently FDA approved for weight loss. Short-term sympathomimetics (phentermine, benzphetamine, diethylpropion, and phendimetrazine) are approved for 3 months of use, with phentermine being the most widely prescribed [27]. AOMs approved for long-term use include the oral medications Orlistat (Xenical and Alli), Phentermine/Topiramate extended release (Qsymia), and Naltrexone/Bupropion extended release (Contrave). Injectable Glucagon-like peptide agonist (GLP-1) receptor agonists (RA) include Liraglutide (Saxenda) and Semaglutide (Wegovy) and the combination GLP-1/GIP agonist Tirzepatide (Zepbound).
It should be noted that all anti-obesity medications are contraindicated in women attempting pregnancy. Thus, in our population, AOMs were only utilized among women electing to defer pregnancy attempts and utilize contraception. The recommendations for cessation of AOMs prior to pregnancy attempts varies based on the half-life of the medication. In the setting of longer-acting GLP1 RAs, the recommended wash-out period may require several months. For example, the manufacturer for Semaglutide advises waiting at least 2 months after stopping the medication to attempt pregnancy and it is suggested to wait at least 1 month following Tirzepatide [28]. Given that Semaglutide and Tirzepatide are titrated once monthly (maximum dose achieved after 5–6 months) and there is a 1-2-month waiting period following cessation of the medication prior to pregnancy attempts, these medications were generally only utilized in individuals willing to defer pregnancy for at least 6–12 months. MICOR uniquely offers medication counseling, management, and monitoring for women in the program on AOMs with goals of future fertility and childbearing.
As mentioned above, after taking the time to discuss the complex interaction between fertility, obesity and pregnancy outcomes, many women elected to defer pregnancy/fertility treatments to focus on weight loss. When we assessed for differences between those women who were willing vs. not willing to focus on weight loss, we found women willing to defer pregnancy attempts were less likely to have a diagnosis of diabetes or anxiety. They also had a higher AMH. It is logical that baseline ovarian reserve status would factor into the decision to postpone pregnancy attempts. Surprisingly, there was no difference in other medical or gynecologic factors such as presence of other metabolic conditions such as hypertension, hyperlipidemia, prior pregnancy, history of infertility, or other gynecologic diagnoses such as PCOS. While the authors originally hypothesized that metabolic co-morbidities may provide an impetus for focused weight loss prior to pregnancy, women who did not defer pregnancy attempts still elected to engage in tailored nutrition and physical activity plans aimed at gentle weight loss and weight maintenance. Indeed, the average weight loss at 3 months among those women who did not desire to postpone pregnancy attempts was − 2.5% and almost one third of women (28.2%) still achieved a > 5% weight loss.
The MICOR program was designed to provide personalized weight management plans for the treatment of obesity and incorporate family building goals, treatment of reproductive disorders and mitigation of obstetrical risks; for some MICOR patient this meant electing to continue pregnancy attempts. Similarly, while national guidelines suggest that weight loss should be encouraged in all women with obesity prior to pregnancy [12], this may not be an appropriate strategy in certain populations especially those with advanced reproductive age. For example, a study examining cumulative live birth rates following 51, 959 cycles of IVF found that the age-related decline in fertility had a greater impact on cumulative live birth rates at older reproductive ages as opposed to BMI [29]. In this case, the time it takes to achieve clinically significant weight loss may be more detrimental to chance of a future live birth than proceeding immediately with fertility treatments [3]. Furthermore, the data regarding the impact of weight loss on fertility treatment success is mixed with most randomized-controlled trials failing to demonstrate improved live birth rates following pre-conception weight loss [3, 4, 30, 31]. While weight loss is consistently associated with improved rates of ovulation, the impact of weight loss on pregnancy and live birth rates among norm-ovulatory women with infertility is less clear [30]. For example in the FIT-PLEASE study 379 women with unexplained infertility and obesity were randomized to either a 16-week pre-conception intensive intervention including meal replacements and pharmacotherapy (Orlistat) or a standard group with increased physical activity without targeted weight loss [31]. While the intervention group achieved an average of 7% weight loss, there was no difference in the primary outcome of a healthy live birth. Most randomized controlled trials (RCTs) that have assessed weight loss prior to IVF similarly do not demonstrate improvements in live birth [32–35], although there are some small studies that have documented significant improvements [36, 37]. A recent systematic review and meta-analysis that included 16 studies (total n = 3,588 participants) found that while women randomized to a weight loss intervention prior to pregnancy attempts were more likely to become pregnant, they were not more likely to achieve a live birth [38]. Thus, while pre-conception weight loss is important to promote healthier pregnancies, it is not clear that all women will experience an improved chance of a live birth. This complicated relationship between obesity, reproductive age, and infertility, is why more recent guidelines from national reproductive societies such as the American Society of Reproductive Medicine (ASRM), recommend against BMI cutoffs for reproductive treatment [3].
To try to understand pregnancy outcomes within the MICOR population we examined pregnancy and miscarriage rates within the first 6 months of attempted conception. While those individuals who initially elected to defer pregnancy to focus on weight management were less likely to become pregnant, women who ultimately achieved clinically significant weight loss (> 5%) by 6 months demonstrated higher pregnancy rates when compared to those who did not achieve > 5% weight loss. There was no difference in miscarriage rates. As discussed above, the data regarding improved fertility among normo-ovulatory women with obesity is conflicting. It is worth noting that some studies raise concerns about an increased risk of miscarriage in the setting of weight loss immediately prior to conception [28]. For example in the FIT-PLEASE study discussed above a trend towards increased risk of first trimester spontaneous abortion (SAB) (33.3% versus 23.7%), although this did not meet statistical significance [31]. When the authors pooled their results with other small studies, they did see a statistically significant increased risk of SAB, which they hypothesized may be related to vitamin or micronutrient deficiencies [31]. In our study we specifically looked at women who achieved pre-pregnancy weight loss and we did not see a difference in risk of miscarriage among women with > 5% weight loss. However, it will be important to assess the correlation between weight loss and SAB outcomes in larger studies.
Strengths of this study include description of a novel treatment model that incorporates patient family building goals, individualized risk assessment, and personalized weight navigation care plans in tandem with reproductive health. This model also allows for a real-life assessment of treatment strategies as opposed to a single weight loss intervention. Limitations include the retrospective design, overall small sample size, and absence of a control group undergoing standard weight loss therapy. Additionally, there was high attrition in patient numbers. Only 70.5% of subjects returned for follow up at 3 months and 33.7% of patients returned for follow-up at 6 months. This drop in participation is mainly due to patients either choosing not to continue with the program or becoming pregnant (13.1%), at which point weight loss data could no longer be collected. This range of dropout rates is consistent with other weight loss programs, which report dropout rates ranging from 10–80% [39]. Pregnancy data must also be interpreted with caution given that many patients had infertility and pregnancy attempts included a range of fertility treatments. Finally, as multiple weight loss treatments were utilized, it was not possible to determine the effectiveness of any singular treatment modality in this population.
The impact of obesity on reproduction and pregnancy outcomes is significant and complicated. While it is important for women to be aware of the reproductive risks related to obesity, providing risk counseling without a viable mitigation strategy can leave patients feeling frustrated, discouraged, stigmatized, and isolated [40, 41]. This is especially the case in a population that already struggles with a pervasive form of social bias and stigma [14]. Utilizing a compassionate patient-centered and multidisciplinary approach to weight loss and fertility offers tangible and multifaceted options for achieving patients’ goals.
Conclusion
In conclusion, we report that when provided with personalized weight management treatment plans that consider reproductive goals, women are eager to focus on their health. Among baseline characteristics, medical comorbidities, and reproductive/fertility diagnoses, only decision to defer pregnancy was associated with achieving clinically significant weight loss. As rates of obesity continue to rise it is critical to understand how to best treat and care for this population of women trying to manage family building desires, reproductive risks and individual health.
Electronic supplementary material
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Abbreviations
- BMI
Body Mass Index
- REI
Reproductive Endocrinology and Infertility
- MICOR
Michigan Interdisciplinary Clinic for Obesity and Reproduction
- MFM
Maternal Fetal Medicine
- ABOM
American Board of Obesity Medicine
- AOMs
Anti-Obesity Medications
- PCOS
Polycystic Ovary Syndrome
- GLP-1
Glucagon-Like Peptide
- RA
Receptor Agonist
- ASRM
American Society for Reproductive Medicine
- SAB
Spontaneous Abortion
Author contributions
SS designed the study, wrote the main manuscript text, and prepared all figures. DS and JS extracted all data from the medical records, assisted with analysis and edited all manuscript drafts. MM assisted with study conceptualization and edited all drafts of the manuscript. CJ performed the statistical analysis and prepared the initial drafts of the tables. MC, SP, ARJ, AO all reviewed the manuscript and provided input on design and revisions. All authors have reviewed the manuscript.
Funding
There are no funding sources to declare.
Data availability
No datasets were generated or analysed during the current study.
Declarations
Ethics approval and consent to participate
Ethical approval of this study was granted by the University of Michigan Institutional Review Board (HUM00227298). Informed consent was waived as this is a retrospective review of existing data included in the standard care of patients.
Consent for publication
Not applicable.
Competing interests
The authors declare no competing interests.
Footnotes
Publisher’s note
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References
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Data Availability Statement
No datasets were generated or analysed during the current study.