- Academic Editor
†These authors contributed equally.
Background: The number of individuals who are underweight as well as
overweight is increasing worldwide and is known to lead to menstrual disorders
and subfertility. Data regarding the prevalence of infertility in Austrian women
are lacking. This study aimed to determine the prevalence of a pathologically low
and high body mass index (BMI) in Austrian patients with infertility and to
evaluate the live birth rate (LBR) after assisted reproductive technologies
(ARTs) compared with normal weight patients. Methods: A total of 585
couples with infertility who sought treatment at a single center between April
2017 and April 2019 were included in this retrospective study. The patients were
categorized into study group 1 (BMI
Globally, infertility is estimated to affect 5%–15% of all couples during their reproductive years [1]. The American Society for Reproductive Medicine (ARSM) defines infertility as a couple’s inability to conceive after a period of 12 months of regular unprotected intercourse [2, 3]. Female factors have been identified in 33%–41% and male factors in 25%–39% of the affected couples, whereas shared factors and factors of unknown origin account for 9%–39% of the cases [4, 5].
Overweight and obesity are becoming more prevalent in both men and women and
often coexist with hypertension and insulin resistance (metabolic syndrome) [6].
According to a health survey in 2014, 39% of all Austrian women had a body mass
index (BMI) of
Being underweight (BMI
With regard to infertility treatments, high BMI (
Some studies have indicated that patients with obesity produced oocytes of inferior quality during assisted reproductive technology (ART) cycles and had lower clinical pregnancy rates (CPRs) [24, 25]. In comparison, underweight patients have been reported to exhibit no significant differences in oocyte quality or CPR during ART cycles compared with women of normal BMI [20, 24, 25].
This study aimed to determine the prevalence of pathological BMI in women trying to conceive who were treated at the University Hospital for Gynecological Endocrinology and Reproductive Medicine, Medical University Innsbruck between April 2017 and August 2020. Furthermore, the impact of BMI on menstrual cycle, laboratory parameters, infertility duration as well as treatment characteristics and outcomes in terms of CPR and the live birth rate (LBR) were investigated. To the best of our knowledge, this is the first study to analyze the prevalence of pathological BMI in patients with infertility in Austria as well as their baseline characteristics, treatment features, and outcomes.
A total of 958 couples with infertility who presented for their first
appointment to the university hospital for Gynecological Endocrinology and
Reproductive Medicine, Medical University Innsbruck, Austria, between April 2017
and April 2019 were included in this retrospective study. Couples with female age
Inclusion and exclusion of patients in the study.
Inclusion criteria were infertility, infertility treatment, female age 18 to 39 years, and known BMI. Exclusion criteria were female age 40 years or older, missing BMI information, no infertility treatment.
Demographic data, including female age, BMI at first presentation and at start of infertility treatment, laboratory values including hormonal and metabolic parameters, as well as the administered infertility treatment and its outcome were manually extracted from the patient’s electronic medical record. If any of the variables could not be obtained, they were considered missing. The BMI at first presentation was obtained anamnestically, and in cases where it seemed inconsistent, weight and height were measured.
All couples underwent a standardized diagnostic work-up, including two hormonal
analyses during one menstrual cycle (follicular and luteal phases), sonographic
and/or laparoscopic tubal evaluation, and two semen analyses. Pathospermia was
diagnosed if at least one parameter (concentration and/or progressive motility
and/or morphology) was pathological in both semen specimens according to the WHO
criteria [26]. Those with normal female BMI were directly offered infertility
treatment, including ovarian stimulation either with low dose gonadotropins or
with clomiphene citrate for timed sexual intercourse or intrauterine insemination
as well as ART, such as in vitro fertilization (IVF) or intracytoplasmic
sperm injection (ICSI), according to the results of the diagnostic workup. Women
with infertility who had a BMI of
Patient characteristics were summarized using mean and standard deviation (SD) for normally distributed continuous variables, median and interquartile range (IQR) for non-normally distributed continuous variables, and percentages for categorical variables. To determine significant differences among the three study groups, nonparametric tests were used because the data were not normally distributed. Fisher’s exact test (categorical variables) and Kruskal–Wallis test (continuous variables) were applied. All analyses were performed using the R programming language (version 4.0.5, R-foundation, Vienna, Austria) on Mac.
A total of 170 couples met the inclusion criteria (Table 1). According to female BMI, 35 of these were allocated to study group 1, 40 to study group 2, and 95 to the control group (Fig. 1). The prevalence of low BMI in our study population was 5.9%, whereas that of high BMI was 6.7%. The baseline characteristics of the study groups were comparable, except for gravidity and parity, which were significantly higher in group 2 (p = 0.001 and p = 0.01, respectively) (Table 1). With a median infertility duration of 3 years (IQR 2, 6.5) study group 2 showed a longer period of infertility before first presentation than the other groups, although this difference was not statistically significant. Of the underweight patients, only two reported a known eating disorder.
Characteristics | Study group 1 | Study group 2 | Control group | p value |
---|---|---|---|---|
BMI |
BMI |
BMI 19–29.9 kg/m | ||
Patients, n | 35 | 40 | 95 | |
Age (years) | 30 [27, 33.5] | 33 [28.5, 35] | 32 [28, 36] | 0.178 |
BMI (kg/m |
18.16 |
33.27 |
22.77 |
|
BMI stimulation° | 18.28 |
33.46 |
||
Infertility duration (years) | 1.4 [1, 2] | 3 [2, 6.5] | 2 [1, 3] | 0.001* |
Gravidity | 0.29 |
0.95 |
0.26 |
0.001* |
Parity | 0.17 |
0.42 |
0.17 |
0.01* |
Number of miscarriages | 0.06 |
0.15 |
0.05 |
0.136 |
Known eating disorder | 2 (5.7%) | 0 | 0 | |
Smoking | 10 (28.6%) | 8 (20%) | 17 (17.9%) | 0.409 |
Endometriosis | 6 (17.1%) | 6 (15%) | 13 (13.7%) | 0.840 |
PCOS | 10 (28.6%) | 13 (32.5%) | 5 (5.3%) | |
Irregular menstrual cycles | 9 (36%) | 12 (31.6%) | 25 (28.7%) | 0.756 |
Hyperandrogenism | 2 (5.7%) | 6 (15%) | 12 (12.6%) | 0.427 |
Cardiovascular co-morbidities | 0 | 2 (5%) | 2 (2.1%) | 0.505 |
Partner with pathospermia | 6 (20%) | 14 (35.9%) | 25 (34.7%) | 0.281 |
FSH (U/L) | 6.8 [4.9, 8.4] | 6.3 [5.1, 7.7] | 6.1 [5, 7.8] | 0.564 |
LH (U/L) | 6.4 [4.6, 8.9] | 5.2 [3.7, 6] | 5.1 [3.6, 7.2] | 0.143 |
Estradiol (ng/L) | 52 [37, 83] | 47 [31.5, 59] | 55 [38, 80.3] | 0.386 |
Testosterone (µg/L) | 0.28 [0.2, 0.4] | 0.28 [0.2, 0.3] | 0.25 [0.2, 0.3] | 0.398 |
AMH (µg/L) | 3.68 [2, 6.1] | 2.69 [1.1, 4.6] | 2.48 [1.3, 4.8] | 0.229 |
BMI, Body Mass Index (kg/m
*p
° of the 87 patients with BMI
Data are presented as mean
In women with low and high BMI, a tendency toward a higher prevalence of polycystic ovarian syndrome (PCOS) diagnosed according to the Rotterdam criteria was observed [27] compared with women of normal weight. Although not statistically significant, this was most pronounced in women with obesity. Accordingly, overweight women showed clinical signs of hyperandrogenemia (acne, hirsutism, and effluvium) more often than underweight women. Although cardiovascular comorbidities were more frequent in patients with obesity, hypothalamic ovarian insufficiency was observed more often in underweight patients but did not reach statistical significance.
Baseline hormone levels, such as gonadotropins, estradiol, androgens, and anti-Mullerian hormone (AMH) did not differ significantly in the study population. Clinically, menstrual cycle disorders were tendentially more frequent in women with pathological BMI. While 36% of women with low BMI and 31.6% of those with high BMI reported irregular cycles, only 28.7% did so in the control group (p = 0.756). The prevalence of oligomenorrhea and amenorrhea was the highest in study group 1.
Considering the male partners of the women in our study population, the prevalence of pathospermia was comparable among the study groups and the control group.
Couples were offered infertility treatment according to the results of the
diagnostic workup. However, in this study, the focus was on ART cycles (Table 2).
Overall, 112 patients underwent at least one cycle of controlled ovarian
stimulation (controlled ovarian stimulation (COS); 22 patients in study group 1,
27 in study group 2, and 63 in the control group). Altogether, in study group 1,
29 cycles of COS were performed, compared with 35 cycles in study group 2 and 110
cycles in the control group. Of these, 12 cycles (41.4%) were followed by a
fresh embryo transfer in study group 1, 16 (45.7%) in study group 2, and 52
(47.3%) in the control group. In the remaining cycles, all resulting embryos
were frozen owing to ovarian hyperstimulation syndrome or other reasons. The
average number of COS cycles per couple was 1.32
Study group 1 | Study group 2 | Control group | p value | ||
BMI |
BMI |
BMI 19–29.9 kg/m | |||
n (patients) COS | 22 (62.9%) | 27 (67.5%) | 63 (66.3%) | ||
n (COS cycles) | 29 | 35 | 110 | ||
n (fresh transfers after COS) | 12 (41.4%) | 16 (45.7%) | 52 (47.3%) | 0.861 | |
COS cycles per patient | 1.32 |
1.3 |
1.75 |
0.480 | |
n (patients) FET | 32 (91.4%) | 31 (77.5%) | 74 (77.9%) | ||
FETs per patient | 1.68 |
1.63 |
2 |
0.485 | |
n (transfers total fresh + FET) | 44 | 47 | 126 | ||
CPR | 17 (38.6%) | 22 (46.8%) | 52 (41.3%) | 0.742 | |
LBR | 12 (27.3%) | 15 (31.9%) | 28 (22.2%) | 0.381 | |
First COS cycle characteristics | |||||
Stimulation duration (days) | 12 [10, 13] | 12 [11, 15] | 11 [9, 13] | 0.021* | |
Gonadotropin dose daily (units) | 186.3 [152.1, 225] | 225 [192.5, 225.8] | 225 [175, 225] | 0.335 | |
n of MII oocytes | 10 [9, 14.5] | 10 [4, 16] | 9 [5, 14.8] | 0.640 | |
n of good quality embryos | 2.5 [2, 5] | 3 [1, 5] | 2.5 [1, 5] | 0.843 |
ART, assisted reproductive technology; BMI, Body Mass Index (kg/m
*p
Data are presented as mean
Of the patients undergoing ART, 32 underwent at least one frozen–thawed embryo
transfer (FET) in study group 1, 31 in study group 2, and 74 in the control
group. Accordingly, the mean number of FET per patient was 1.68
Summing up the number of fresh embryo transfers after COS and FETs, overall, 44 embryo transfers were performed in study group 1, 47 in study group 2, and 126 in the control group, which resulted in CPRs of 38.6% (n = 17), 46.8% (n = 22), and 41.3% (n = 52), respectively. The odds ratio for obtaining a clinical pregnancy was 0.90 [0.44–1.80] for women with low BMI and 1.25 [0.64–2.46] for those with high BMI. The LBR was comparable among the three BMI groups and amounted to 27.3% (n = 12), 31.9% (n = 15), and 22.2% (n = 28), respectively. The odds ratio for obtaining a live birth was 1.31 [0.58–2.84] for women with low BMI and 1.64 [0.77–3.43] for those with high BMI.
When the characteristics of the first COS cycles were compared (Table 2), patients with high BMI required a significantly longer stimulation (12 days [IQR 11, 15] vs. 12 days [IQR 10, 13] and 11 days [IQR 9, 13], p = 0.021) than those with normal BMI. The median daily gonadotropin dose was comparable, but owing to the longer duration of stimulation, patients in study group 2 required a higher total gonadotropin dose. The number of mature oocytes (MII oocytes) and good quality embryos obtained in the first cycle did not differ significantly among the groups.
In this study, the prevalence of pathological BMI values in Austrian patients
with infertility was determined to be 5.9% for a BMI of
Overweight women showed higher gravidity and parity when first presenting to our
center for fertility treatment. All other baseline demographic as well as
clinical and laboratory characteristics were comparable for the various BMI
categories. However, PCOS and menstrual cycle disorders tended to be more
frequent in women with low and high BMI. The prevalence of pathospermia in the
male partners was comparable in all study groups. In women undergoing ART, CPR
and LBR were comparable among the three BMI classes. In the first cycles of COS,
a longer duration of stimulation as well as a higher total gonadotropin dose was
observed in women with BMI
The prevalence of underweight in our patients with infertility is comparable to
that described in the general Austrian female population, which is 10.3% in
women aged 15–29 years and 4.8% in those aged 30–44 years [7]. These
percentages are slightly higher than the ones reported in our neighboring country
Germany, where the prevalence of underweight is 4.9% for women aged 18–29 years
and 4.4% for those aged 30–39 years [28]. In the general European female
population aged
The higher baseline gravidity and parity observed in women with a BMI of
Conventionally, PCOS has been associated with obesity. A meta-analysis by Lim et al. [38] reported that women with obesity have an odds ratio of 2.77 for the development of PCOS compared with women of normal weight. Accordingly, other studies have documented a pathologically high BMI in 38%–88% of women with PCOS [39]. In line with these findings, we found a tendentially higher prevalence of PCOS in women with high BMI. However, in women with low BMI too, PCOS was more frequent than that in the controls. So far, few studies have examined the prevalence of underweight in patients with PCOS. Contrary to our results, Anastasiou et al. [40] found that only 1.5% of the 1269 women with PCOS were underweight. Further studies are, therefore, needed to clarify the relationship between low BMI and PCOS.
In accordance with previous studies [41, 42, 43, 44], our patients with low and high BMI presented with menstrual cycle disorders more frequently than those with normal BMI, although the difference was not statistically significant. This observation is pathophysiologically plausible as both hypoleptinaemia due to diminished fat stores and hyperleptinaemia due to obesity have been reported to suppress the HPG axis [45], thus leading to oligomenorrhea and amenorrhea and, consequently, subfertility.
Only two patients with a BMI of
As we considered a BMI of
With regard to the ART cycles (fresh embryo transfers and FETs) performed in our
study population, we found that CPR and LBR were similar for all three study
groups. In case of patients with low BMI, our results are in line with two
recently published systematic reviews [48, 49] and a large retrospective cohort
study [50]. For overweight women and those with obesity, however, several
previous studies have reported a lower LBR [24, 49, 51, 52, 53, 54, 55]. A recent meta-analysis
observed a nonlinear association between BMI and LBR, with a relatively flat
curve over a broad BMI range of 16–30 kg/m
To avoid bias due to adaptation of treatment protocols according to the results of the first COS cycle, the characteristics of the first COS cycle were evaluated separately. In accordance with previous studies [57, 58], we found a significantly higher duration of stimulation and total gonadotropin dose in patients with obesity. However, the number of MII oocytes and good quality embryos was not reduced in patients with obesity. The literature regarding these outcome measures in patients with obesity is conflicting, possibly because some authors have reported on several treatment cycles whereas others have reported on first treatment cycles only [21]. Further studies are, therefore, required.
Owing to the retrospective design of the present study, data regarding obstetric complications were not available. Nonetheless, previous studies have described an association between low or high maternal BMI and the risk of several pregnancy-related complications. A meta-analysis estimated that 23.9% of any pregnancy complication could be attributed to maternal overweight/obesity. The study found higher risks of gestational hypertensive disorders, gestational diabetes, and large for gestational age at birth in women who were overweight and obese. The risk of preterm birth has been shown to be increased in women with low as well as high BMI [59]. Underweight mothers have also been reported to have increased odds for small for gestational age infants [60]. These studies did not specifically refer to pregnancies from ART, but recent studies have observed similar results for ART pregnancies [61]. As being underweight and overweight often lead to infertility, fertility specialists should be aware not only of the possible difficulties during ART but also of the high risk of obstetric complications in these patient groups. Hence, emphasis should be placed on preconception counselling and adequate prenatal care.
To the best of our knowledge, this is the first study to evaluate the prevalence of pathologically low and high BMI in patients with infertility in Austria. However, our study is limited by the retrospective design, small sample size, limited observation period, and single-center design. Hence, further studies in other Austrian centers are needed to confirm the prevalence of pathologically low and high BMI in patients with infertility in Austria.
The prevalence of low and high BMI in Austrian patients seeking fertility treatment is over 10%. As a higher risk of pregnancy-related complications has been previously reported and the results regarding LBR are conflicting, fertility specialists should be attentive to BMI values in their patients with infertility issues.
LBR, live birth rate; ART, assisted reproductive technology; ARSM, American Society for Reproductive Medicine; BMI, body mass index; SHBG, sex hormone-binding globulin; GnRH, gonadotropin-releasing hormone; CPR, clinical pregnancy rate; SD, standard deviation; IQR, interquartile range; COS, controlled ovarian stimulation; OHSS, ovarian hyperstimulation syndrome; FET, frozen–thawed embryo transfer; HPG, hypothalamo–pituitary–gonadal.
The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.
ALZ, KR, KF and BT designed the research study. KR and LR collected and analyzed the data. All authors contributed to editorial changes in the manuscript. All authors read and approved the final manuscript. All authors have participated sufficiently in the work and agreed to be accountable for all aspects of the work.
Ethics approval: Ethical approval was waived by the local Ethics Committee of the Medical University of Innsbruck (EK: 1272/2019) in view of the retrospective nature of the study and all the procedures being performed being part of routine care. Informed consent was obtained from all individual participants included in the study. Patients signed informed consent for publishing their data.
Not applicable.
This research received no external funding.
The authors declare no conflict of interest.
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