†These authors contributed equally.
Background: One of the characteristics that is directly linked to
polycystic ovary syndrome (PCOS) is body mass index (BMI), and there have been
numerous studies that are pertinent to PCOS patients with high BMI. However,
further research is needed to determine the precise impacts of normal BMI on PCOS
patients’ metabolism and chances of becoming pregnant. Achieving a normal BMI may
enhance glucose metabolism and lower the risk of gestational diabetes in pregnant
PCOS women. By examining the reproductive results of PCOS patients with normal
BMI, this study offers fresh suggestions for the management and alleviation of
clinical symptoms in PCOS patients. Methods: From January 1, 2021 to
April 30, 2022, 133 in vitro fertilization/intracytoplasmic sperm
injection (IVF/ICSI) cases with normal body mass index were enrolled in the
Reproductive Medical Center of Hainan Women and Children’s Medical Centre,
including 77 PCOS patients with normal BMI and 46 non-PCOS patients with normal
BMI, the ovulation induction regimen was used as an antagonist regimen, and the
waist circumference, body mass index, follicle-stimulating hormone (FSH),
luteinizing hormone (LH), LH/FSH, anti-Mullerian hormone (AMH), blood lipids,
homeostasis model assessment of insulin resistance (HOMA-IR), gonadotropin (Gn) dosage between the two groups were
compared, Gn days of use, number of eggs obtained, normal fertilization rate,
normal cleavage rate, number of available embryos, number of high-quality
embryos, embryo implantation rate, clinical pregnancy rate and other indicators.
Results: The endocrine situation between the two groups showed that the
AMH, LH value, LH/FSH value, fasting insulin and HOMA-IR of PCOS group (group 1)
were significantly higher than control group (group 2), and the data between the
two groups were extremely significant (p
Women of reproductive age are frequently affected by the hormonal condition known as polycystic ovary syndrome (PCOS). The hormonal imbalances associated with PCOS can disrupt ovulation, making it harder for women with PCOS to conceive naturally . PCOS has three canonical features: hyperandrogenism/hyperandrogen hirsutism, oligomenorrhagia/anovulation, polycystic ovarian morphology, characterized by an abnormally high antral follicle count (AFC) and increased ovarian volume. One of the most frequent reasons of female infertility, PCOS is a prevalent hormonal disorder that impacts about 7–8% of women of reproductive age . High body mass index (BMI) women are more likely to experience infertility and irregular menstrual cycles, and obesity is one of the reasons that is directly linked to PCOS . The two most prevalent clinical kinds of PCOS are non-obese PCOS with a BMI in the normal range and obese PCOS with a BMI in the overweight or even obese range .
Intracytoplasmic sperm injection (ICSI) and conventional in vitro fertilization (IVF) are common fertilization techniques in the field of assisted reproduction and are successful in treating infertility in PCOS patients . Age, BMI, and use of assisted reproductive technologies all independently affect pregnancy outcomes in women with PCOS, according to prior research, but mixed studies of BMI and assisted reproductive technology (ART) have produced conflicting results . To our knowledge, there are many clinical studies on the outcomes of pregnancies in obese women with PCOS and few studies on the outcomes of pregnancies in women with normal BMI using assisted reproductive technology. This is the reason for the restriction on elucidating BMI in conjunction with ART . Therefore, taking into account the potential effects of normal BMI on assisted reproductive technology, this study compares metabolic indicators and IVF/ICSI fertility outcomes in PCOS patients with normal BMI in order to provide guidance for clinical treatment and improve pregnancy success rate.
The retrospective study collected 133 IVF/ICSI cases with normal body mass index
who visited the Reproductive Medical Center of Hainan Women and Children’s
Medical Centre from January 1, 2021 to April 30, 2022, among which patients with
normal BMI PCOS infertility were used as the observation group (group 1, n = 77),
and non-PCOS patients with normal BMI were included in the control group (group
2, n = 46), all aged
The inclusion criteria for infertility refer to the guidelines on diagnostic of infertility , and the criteria are as follows: (1) Normal sexual life is not less than 1 year; (2) No gynecological diseases, normal menstruation; (3) All subjects had normal communication skills and voluntarily participated in this study.
The diagnosis of PCOS is based on the 2003 Rotterdam diagnostic criteria as follows: (1) Two years after menarche, menstrual sparse or amenorrhea occurs; (2) Ultrasound showed the morphology changes of the polycystic ovaries; (3) Problems with high androgens or hirsutism . If two of the above three items are met, polycystic ovary syndrome is achieved.
The exclusion criteria were as follows: (1) Patients with endometriosis; (2) Patients who have previously had surgery to remove one ovary; (3) Bilateral or unilateral tubal effusion; (4) Endometrial abnormalities (intrauterine adhesions, endometrial polyps, submucosal fibroids); (5) Diseases of important organs such as heart, liver, kidney, brain, and lungs; (6) Cushing’s syndrome, congenital adrenal hyperplasia and other endocrine diseases.
Statistics of basic data such as height, weight, waist circumference, bilateral ovarian sinus follicles and so on. Measure hormones such as anti-Mullerian hormone (AMH), follicle-stimulating hormone (FSH), luteinizing hormone (LH) and so on.
Take the antagonist program as ovulation induction program, collect basic information such as patient age and BMI, clinically select the appropriate gonadotropin (Gn) dose, and perform ovulation induction operation . Gn includes gonadotropin or urogonadotropin, regular vaginal ultrasound examination, observe the development of follicles and adjust the dose of the drug, and add gonadotropin releasing hormone antagonist (GnRH-A) when the diameter of the dominant follicle reaches 12–14 mm.
Pregnancy outcomes were judged as follows, serum
Statistics include patient age, follicle-stimulating hormone (FSH), luteinizing hormone (LH), AMH, blood lipids, homeostasis model assessment of insulin resistance (HOMA-IR), number of embryos transferred, clinical pregnancy rate, moderate to severe ovarian hyperstimulation syndrome (OHSS) rate and other indicators.
The data were analyzed with SPSS 26.0 statistical software (IBM Corp, Armonk,
NY, USA), and the measurement data was expressed as
The comparison of the basic conditions and endocrine conditions of the two
groups is shown in Table 1. There was no significant difference (p
|Index||PCOS group with normal BMI (Group 1)||Control group (Group 2)||p value|
|Blood lipids (cm/s)||1.33
|Fasting blood sugar (mmol/L)||4.95
|Fasting insulin (pmol/mL)||12.83
After IVF/ICSI, relevant indicators of the two groups are shown in Table 2.
Analysis of ovulation induction in the two groups showed that the cycle and
average daily growth rate of HCG in group 1 were higher, and the amount of Gn
dosage and Gn days used were lower, and the difference in Gn dosage was extremely (p
|Index||Group 1||Group 2||p value|
|Gn dosage (mlU/mL)||1583.12
|Number of eggs obtained (n)||16.54
|Normal number of fertilizations (n)||10.64
|Normal cleavage number (n)||10.37
|Number of embryos available (n)||7.26
|Number of high-quality embryos (n)||7.32
|Number of implanted embryos (n)||0.69
|Clinical pregnancy rate||61.54%||59.38%||0.854|
Gn, gonadotropin; E
The results of Kendall analysis showed (Tables 3,4)
that the BMI, blood lipid, AMH, and basal testosterone of group 1 were positively
correlated with the HOMA-IR (R
|Index||R value||p value|
|Blood lipids (cm/s)||0.264||0.010|
|Clinical pregnancy rate||–0.035||0.795|
|Index||R value||p value|
|Clinical pregnancy rate||–0.302||0.043|
|Number of high-quality embryos (n)||–0.069||0.586|
Menstrual disruption, infertility, and clinical and biochemical hyperandrogenemia are important clinical characteristics of PCOS . PCOS is usually diagnosed by internationally recognized Rotterdam criteria, the Androgen Excess Society (AES) proposed a simplified diagnostic requirement in 2006 with clinical and/or biochemical hyperandrogenemia simultaneously with oligo/anovulation and polycystic ovaries on ultrasound [13, 14]. Since insulin resistance contributes to obesity in patients, which worsens the severity of clinical symptoms in women with PCOS, it is not currently recognized in diagnostic criteria as a major cause of reproductive and metabolic impairment [15, 16]. BMI is an important indicator for the judgment of obesity, and BMI is closely related to the clinical symptoms of PCOS patients . At present, PCOS patients can improve endocrine and relieve PCOS symptoms through drug treatment, but the complete cure of PCOS can not be achieved, and drugs can not alleviate the patient’s difficulty in conceiving, and there are strong side effects . Therefore, people with PCOS who are of childbearing age still prefer artificial assisted reproductive technology as their first option for getting pregnant. IVF and ICSI are two popular IVF procedures that are currently used to treat infertile women’s inability to conceive a child. They are less risky, safer, more cost-effective, and patient-friendly than other IVF procedures . There have been many studies on the treatment of PCOS patients with IVF/ICSI, but most of them focus on the impact of the two techniques on the metabolism of follicles in patients , effects on pregnancy in patients with high BMI [21, 22], the impact of the two techniques and patients’ menstrual manifestations on pregnancy . This study innovatively started from PCOS patients with normal BMI, explored the differences in clinical features of different patients with normal BMI, and clarified the impact of normal BMI on the clinical characteristics and pregnancy of PCOS patients, so as to provide better clinical treatment for PCOS patients.
Through the analysis of the clinical characteristics of the patients in this
study, the results showed that the AMH, LH value, LH/FSH value, fasting insulin
and HOMA-IR of PCOS patients with normal BMI were higher than those in group 2,
and the data were extremely significant (p
The study showed that after IVF/ICSI in the two groups, the dosage of Gn in
group 2 was extremely significant (p
Although this study comprehensively elaborates the differences in pregnancy metabolism and other indicators between the two groups, there are still many shortcomings. This study’s sample size is still modest, therefore expanding it further is crucial to the study’s reliability and applicability in general. The next step in improving this study is to combine it with PCOS patients of various BMIs, despite the fact that it was originally conducted on PCOS patients with normal BMI. At the same time, the mechanism of insulin on PCOS patients still needs further research, which may be an important reason for limiting the further development of PCOS treatment. The treatment of PCOS is still a global problem, and it is believed that through more and more in-depth research by excellent medical workers, the creation of a more complete PCOS treatment system is just around the corner.
In summary, during the treatment of PCOS patients with normal BMI, insulin resistance should be treated simultaneously with the control of hyperandrogen, and weight loss is recommended despite a normal body mass index. For PCOS patients with normal BMI, it is recommended to reduce the dose of Gn clinical treatment, which not only benefits the pregnancy of PCOS patients, but also effectively reduces the risk of OHSS in PCOS patients.
The datasets used or analyzed during the current study are available from the corresponding author on reasonable request.
NM, JZ and WL jointly designed the research content. NM and JZ contributed equally. NM conducted the clinical research and manuscript editing. JZ participated in the clinical research and was responsible for data analysis. WL was the guarantor of the integrity of the entire research, and was responsible for manuscript review and research technical support. 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 to take public responsibility for appropriate portions of the content and agreed to be accountable for all aspects of the work in ensuring that questions related to its accuracy or integrity.
This study was approved by the Medical Ethics Committee of Hainan Women and Children’s Medical Center (HNWCMC) (Approval number: HNWCNC.2023.). Retrospective studies did not obtain informed patient consent.
We would like to express our gratitude to all those who helped us during the writing of this manuscript. Thanks to all the peer reviewers for their opinions and suggestions.
This project was supported by the Natural Science Foundation of Hainan Province (Grant No.: 820RC771); The Key R&D Projects of Hainan Province (Grant No.: ZDYF2022SHFZ074); Hospital-Level Task Book of Hainan Women and Children’s Medical Center (Grant No. 2020YJ01).
The authors declare no conflict of interest.
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