Association between Vitamin D and pregnancy in women with polycystic ovary syndrome: a case-control study from Beijing, China

doi:10.21203/rs.3.rs-1943595/v2

Download PDF

Research Article

Association between Vitamin D and pregnancy in women with polycystic ovary syndrome: a case-control study from Beijing, China

https://doi.org/10.21203/rs.3.rs-1943595/v2

This work is licensed under a CC BY 4.0 License

Version 2

posted

You are reading this latest preprint version

Background

Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility. Several evidence show that vitamin D may be beneficial to female reproduction in PCOS. However, few studies have been done to the correlation between vitamin D levels and pregnancy in PCOS patients after ovulation induction therapy.

Methods

We enrolled a total of 200 newly diagnosed anovulatory infertile patients with PCOS (experimental group) and 200 healthy women of childbearing age (control group) between June 2016 and September 2018. The experiment group treated with Letrozole for inducing ovulation. We investigated the pregnancy rate for patients with PCOS and studied correlation of pregnancy rate and levels of 25-(OH) D3 in patients with PCOS. Then we evaluated serum 25-(OH) D3 levels between the two subgroups, with the experimental group divided into vitamin D-deficient and vitamin D non-deficient subgroups and analyzed their respective pregnancy rates.

Results

The mean serum 25-(OH) D3 level in the experimental group was significantly lower than that in the control group (14.57 ± 5.86 ng/mL vs. 22.24 ± 6.73 ng/mL, respectively; t = 12.190, P < 0.05). Of the 200 patients in the experimental group, 149 patients completed the ovulation-induction regimen, comprising 72 patients who became pregnant and 77 patients who failed to become pregnant—generating a pregnancy rate of 48.32%. We noted that the serum 25-(OH) D3 level in the pregnant patients was significantly higher than that in the non-pregnant patients (16.06 ± 5.80 ng/mL vs. 13.54 ± 5.88 ng/mL, respectively; t = 2.635, P < 0.05). Additionally, the pregnancy rate was 43.89% in the vitamin D-deficient group compared to 67.86% in the vitamin D non-deficient group, with the latter significantly higher compared to the former group (χ² = 5.269, P < 0.05).

Conclusions

Our results demonstrate that vitamin D deficiency is common in women with PCOS and vitamin D appears to play a beneficial role in PCOS patients undergoing an ovulation-induction regimen. Therefore, monitoring the serum vitamin D level in PCOS patients and timely and appropriate vitamin D supplementation are essential to improve the pregnancy success rate of infertile women with PCOS.

Polycystic ovary syndrome

Vitamin D

Pregnancy

Polycystic ovary syndrome (PCOS) is a common gynecological endocrine disease, characterized by long-term anovulation and hyperandrogenism[1, 2]. Other clinical manifestations are menstrual disorders, hirsutism, acne, and obesity[3]. PCOS is one of the primary causes of anovulatory infertility and closely associated with levels of various sex hormones, usually accompanied by insulin resistance (IR) and glucose and lipid metabolic disorders. The etiology of PCOS remains unclear, although some studies have shown that PCOS is related to environmental and genetic factors [4–6].

Much evidence demonstrates that the reproductive potential is reduced in women with PCOS, due to ovulatory status, oocytes, embryo and endometrial competence and so on[7]. Vitamin D is a steroid hormone and has effects of calcium homeostasis and bone mineralization. Recent studies show that vitamin D is related to female reproduction and may have beneficial effects on female infertility[8]. Vitamin D plays a crucial role in the PCOS and endometriosis and in successful in vitro fertilization and pregnancy outcomes [9–11]. The vitamin D deficiency is widely prevalent in PCOS patients, with approximately 67–85% of patients affected[12]. Some studies suggested that a low vitamin D was associated with a pathogenesis of metabolic disorders in PCOS, and vitamin D deficiency was correlated with PCOS symptoms such as ovulatory dysfunction and infertility [13, 14]. Nevertheless, there are few studies focused on the correlation between vitamin D levels and pregnancy in patients with PCOS undergoing ovulation regiment.

In the present study, we clarified the correlation between vitamin D levels and PCOS by comparing serum vitamin D between PCOS patients and healthy women of child-bearing age and evaluated whether vitamin D levels influenced clinical pregnancy rates in PCOS patients who underwent an ovulation-induction regimen. Our study adds the understanding of the association of Vitamin D with pregnancy rates in PCOS patients and provides a new rationale for diagnosis and treatment of infertility patients with PCOS.

Study population

Between June 2016 and September 2018, we enrolled 200 newly diagnosed PCOS patients with infertility (the experimental group) and 200 healthy women of childbearing age (the control group) at the Obstetrics and Gynecology Clinic of Beijing’s Anzhen Hospital, affiliated with Capital Medical University.

The inclusion criteria for the experimental group were patients

(1) confirmed to have PCOS in accordance with the Rotterdam diagnostic criteria[12] and meeting at least two of the following three criteria: 1) a clinical manifestation of infrequent ovulation or anovulation; 2) clinical or biochemical indicators that suggested the presence of hyperandrogenemia; and 3) ultrasonographic examination (performed 3–5 days after menses or bleeding after progesterone withdrawal) showing that both ovaries had over 12 small follicles with diameters of 2–9 mm—i.e., polycystic changes in the ovaries or increased ovarian volume (ovarian volume = 0.5 × length × width × thickness). Additional criteria after meeting two of the three abovementioned criteria (except for other causes of hyperandrogenemia such as hyperprolactinemia and thyroid disease, congenital adrenocortical hyperplasia, Cushing's syndrome, or androgen-secreting tumors). (2) women who failed to become pregnant after 12 months of normal sexual intercourse without contraception, and diagnosed as ovulatory infertility by ultrasonic monitoring of follicular development, then signed informed consent for ovulation-induction therapy; and (3) women who had not taken insulin, contraceptive drugs, or other medications that might have influenced sex hormone levels within the past 3 months. Our control group consisted of healthy women of child-bearing age who underwent routine physical examination and who exhibited regular menstrual cycles and were age, BMI-matched to our experimental group, and clinical/biochemical features of hyperandrogenism were excluded. PCOS patients and the control group have the same conditions of sun exposure, intake of a diet richer in vitamin D, and normal liver and kidney functions.

The exclusion criteria were patients (1) with chronic diseases such as thyroid disease, diabetes, hypertension, cardiovascular disease, or other medical complications; (2) with ovulatory dysfunction caused by hyperprolactinemia, premature ovarian failure, or pituitary or hypothalamic amenorrhea; (3) whose ultrasonographic examination showed abnormal endometrial lesions, uterine malformations, uterine fibroids, or adnexal masses; (4) manifesting bilateral oviductal obstruction; (5) exhibiting severe abnormalities found upon examination of the husband’s semen; (6) exposed (husband or wife) to teratogenic amounts of radiation or poisons, and the exposure of drugs was in the active period; and (7) showing severe liver or kidney dysfunction; (8) showing clinical/biochemical features of hyperandrogenism in control healthy women, such as PCO morphology.

Patient treatment

Detection of 25-(OH) D3 in serum

Fasting blood samples from both groups were collected on the second or third day of menstruation or bleeding after the withdrawal of progesterone, centrifuged for 5 min, and serum was stored at − 20°C for testing. In addition to the evaluation of 25-(OH) D3 levels, blood from the experimental group was also assayed for the levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), progesterone (P), estradiol (E₂), and testosterone (T). Commercially available chemiluminescence immunoassay (CLIA) LIAISON 25-OH Vitamin D total assay kit (DiaSorin, Saluggia, Italy) were used to detect the level of 25-(OH) D3 and all procedures were conducted in strict accordance with the manufacturer’s instructions. Serum levels of FSH, LH, E₂, P, and T were also ascertained using CLIA kits.

Letrozole ovulation-induction therapy

The induction regimen for the experimental group was as follows. (1) After the fasting blood samples were collected according to the menstrual cycle, letrozole was administered orally at 2.5 mg or 5 mg per day with continuous use for 5 days, and the patient was returned to the hospital on the 10th day of menstruation to monitor the development of her follicles ultrasonographical; (2) then, 10,000 units of chorionic Gonadotropin (Livzon, Zhuhai, China)was administered by intramuscular injection when ultrasonography detected one or two mature follicles (i.e., follicles with a diameter ≥ 15 mm). Instructions on sexual activity were provided, and the patients were told to return to the hospital 2 days later to determine whether ovulation occurred; (3) serum human chorionic gonadotropin (HCG) levels were determined 2 weeks after ovulation. If the sample was positive for HCG, the patient underwent transvaginal ultrasonography at 4–5 weeks after ovulation. We observed 3 cycles in this study. If ovulation did not occur in three cycles, it is considered a failure. The PCOS patients were further divided into pregnant and non-pregnant groups depending upon the pregnancy status; and depending on the serum 25-(OH) D3 levels, the PCOS patients were further subdivided into vitamin D-deficient and non-deficient groups(Ovulation induction and controlled ovarian stimulation using letrozole gonadotropin combination: A single center retrospective cohort study).

Observation indicators and evaluation criteria

(1) We monitored serum 25-(OH) D3 levels in the experimental and control groups. The normal range for serum 25-(OH) D3 was 30–100 ng/mL, and relative vitamin D insufficiency was defined as 20 ng/mL ≤ 25-(OH) D3 < 30 ng/mL, while vitamin D deficiency was defined as 25-(OH) D3 < 20 ng/mL; and (2) the height and weight of patients in the experimental group were determined when the fasting blood samples were collected. BMI was calculated using the following formula: BMI = body weight (kg)/height (m) squared. (3) Baseline sex hormone levels of patients in the experimental group were also monitored; (4) the pregnancy rate after letrozole ovulation-induction therapy was determined in the experimental group after 6 months of treatment (the criteria for successful pregnancy were positivity in an early pregnancy test, and an ultrasonographic scan showing an intrauterine pregnancy sac); and finally, (5) the time from the initiation of ovulation-induction therapy to clinical pregnancy (months) in the pregnant patients was assessed.

Statistical analysis

We conducted all statistical analyses using SPSS 22.0 software, and measurement data were expressed as mean ± standard deviation (x ± s). All data conformed to a normal distribution when assessed using a homogeneity test of variance and means of the two samples were compared by Student’s t-test. We set the significance level at α = 0.05. Counting data were expressed as the number of cases and ratios (n, %), and intergroup comparisons were executed using x² tests.

Comparison of serum 25-(OH) D3 levels between the experimental and control groups

Patients in the experimental group were 18–40 years of age, with an average of 29.66 ± 3.80 years; subjects in the control group were 22–39 years of age, with an average of 29.08 ± 3.594 years. The baseline information did not significantly differ between the two groups according to Student’s t-test (P > 0.05). In the experimental group, we noted a total of 165 patients (82.5%) with vitamin D deficiency and 33 patients (16.5%) with relative vitamin D insufficiency; two patients (1%) exhibited normal vitamin D levels. The control group comprised 75 subjects (37.5%) with vitamin D deficiency and 97 subjects (48.5%) with relative vitamin D insufficiency; and the vitamin D level was normal in 28 subjects (14%) (data are presented in Table 1). The mean serum 25-(OH) D3 level in the experimental group was 14.57 ng/mL compared to 22.24 ng/mL in the control group (P < 0.05, Table 2).

Table 1

Serum 25-(OH) D3 levels in the control group and experimental group.
Serum 25-(OH) D3 (ng/mL)	Control Group n (% of total)	Experimental Group n (% of total)
25-(OH) D3 < 20 ng/mL	165(82.5%)	75(37.5%)
20 ng/mL ≤ 25-(OH) D3 < 30 ng/mL	33(16.5%)	97(48.5%)
30 ng/mL ≤ 25-(OH) D3 ≤ 100 ng/mL	2(1%)	28(14%)
total	200(100%)	200(100%)

Table 2

Comparison of serum 25-(OH) D3 levels between the experimental and control groups (‾x ± s).
	Experimental group (n = 200)	Control group (n = 200)	t	P
25-(OH) D3 (ng/mL)	14.57 ± 5.86	22.24 ± 6.73	12.190	0.000

Pregnancy outcomes after ovulation induction in the experimental group

Of the 200 PCOS patients in the experimental group, we noted 51 patients who did not complete the 6 months of ovulation-induction therapy or were lost to follow-up by March 2019. We thus enrolled 149 patients who completed the ovulation-induction regimen into the experimental group—including 72 patients who became pregnant and 77 patients who failed to become pregnant—for a pregnancy rate of 48.32% (Table 6).

Comparison of serum 25-(OH) D3 levels between the pregnant and non-pregnant groups

When we compared the baseline information between pregnant and non-pregnant groups, we found no significant differences in age, BMI, or baseline sex hormone levels (FSH, LH, P, E, and T) between the two groups (P > 0.05, Table 3). We then compared serum 25-(OH) D3 levels between the pregnant and non-pregnant groups and observed that the 25-(OH) D3 in serum was lower in the non-pregnant group (13.54 ng/mL) compared to the pregnant group (16.06 ng/mL) (P < 0.05, Table 4).

Table 3

Comparison of clinical parameters between the pregnant and non-pregnant subgroups within the experimental group (‾x ± s).
Parameters	Pregnant group (n = 72)	Pregnant group (n = 72)	t	P
Age (y)	28.97 ± 3.52	29.06 ± 4.05	−0.149	−0.149
BMI (kg/m²)	23.01 ± 3.51	23.22 ± 4.09	−0.346	0.729
FSH (mIU/mL)	6.42 ± 1.99	6.49 ± 2.01	−0.229	0.819
LH (mIU/mL)	8.13 ± 6.09	8.41 ± 5.14	−0.301	0.764
E (pg/mL)	0.82 ± 1.93	0.82 ± 1.93	0.499	0.499
E (pg/mL)	E (pg/mL)	0.82 ± 1.93	0.338	0.499
T (ng/mL)	0.53 ± 0.19	0.53 ± 0.19	−1.629	0.106

Table 4

Comparison of serum 25(OH) D levels between the pregnant and non-pregnant groups (‾x ± s).
	Pregnant group (n = 72)	Non-pregnant group (n = 77)	t	P
25-(OH) D3 (ng/mL)	16.06 ± 5.80	13.54 ± 5.88	2.635	0.009

Comparison of pregnancy rates between subjects with different vitamin D levels

Baseline information on the 149 PCOS patients in the vitamin D-deficient and vitamin D non-deficient experimental groups showed no differences between the patients who were vitamin D-deficient with a 25-(OH) D3 of < 20 ng/mL and the vitamin D non-deficient group that manifested a 25-(OH) D3 ≥ 20 ng/mL. Age, BMI, and baseline sex hormone levels (FSH, LH, P, E, T) also did not differ between the two groups (P > 0.05), as shown in Table 5. We contrasted the pregnancy rates between the vitamin D-deficient and vitamin D non-deficient groups and ascertained that among the 149 PCOS patients in the experimental group, there were 121 patients with vitamin D deficiency and 53 patients who became pregnant, for a pregnancy rate of 43.80%; and that there were 28 vitamin D non-deficient patients (i.e., with a normal vitamin D level or relative vitamin D insufficiency) and 19 patients who became pregnant, for a pregnancy rate of 67.86%. The pregnancy rate for vitamin D non-deficient patients was therefore significantly higher than that for the vitamin D-deficient patients (x² = 5.269, P < 0.05; Table 6).

Table 5

Comparison of parameters between the vitamin D-deficient and vitamin D non-deficient groups (‾x ± s).
Parameters	Vitamin D-deficient group (n = 121)	Vitamin D non-deficient group (n = 28)	t	P
Age (y)	28.79 ± 3.97	30.00 ± 2.69	−1.525	0.130
BMI (kg/m²)	23.22 ± 3.85	23.22 ± 3.85	0.680	0.498
FSH (mIU/mL)	6.33 ± 1.95	6.33 ± 1.95	−1.610	0.109
LH (mIU/mL)	8.50 ± 5.91	8.41 ± 5.14	1.022	0.309
P (pg/mL)	0.80 ± 1.95	0.48 ± 0.36	0.882	0.379
E (pg/mL)	60.00 ± 45.13	46.46 ± 27.42	1.521	1.521
T (ng/mL)	0.56 ± 0.20	0.53 ± 0.16	0.734	0.464

Table 6

Comparison of pregnancy rates between vitamin D-deficient and vitamin D non-deficient groups.
Serum 25-(OH) D3 (ng/mL)	N	Pregnant (n)	Non-pregnant (n)	Rate of pregnant of total (%)
Vitamin D-deficient group	121	53	68	43.8
Vitamin D non-deficient group	28	19	9	67.86
total	149	72	77	48.32

Women with PCOS, when compared to the controls demonstrated low fertility potential, which may be related to ovulation status, endometrial function, oocyte quality, etc[15]. Although some medical treatments (Letrozole and clomiphene) have been adopted for ovulation induction, the pregnancy rate remains relatively low. Recently, some studies manifested the protective role of vitamin D in female reproduction, which leads to the possibility of vitamin D in the treatment of infertility in PCOS patients. In this study, we found that the serum vitamin D level of PCOS patients was lower than that of healthy women of childbearing age. In addition, the average serum level of 25-(OH) D3 in pregnant women was higher than that in non-pregnant women in PCOS patients of childbearing age who received letrozole ovulation induction therapy. Finally, the pregnancy rate of patients without vitamin D deficiency is higher than that of patients with vitamin D deficiency. Our study implies that vitamin D might represent a therapeutic approach to female infertility in the women with PCOS.

Vitamin D is a lipid-soluble vitamin that belongs to the steroid hormone family. Vitamin D, administered via the skin or food, is metabolized into its active form 25-(OH) D3 in the liver and in the kidneys by 25-hydroxylase and 1a-hydroylase, 1,25(OH)2D3[8]. Vitamin D status of the human body is best indicated by the circulating level of 25(OH)D3, vitamin D derivative, due to 25-(OH) D3 exhibits a longer half-life and remains unaffected by calcium uptake[16]. The biologic functions of vitamin D are mediated by vitamin D receptors that are present in various tissues—including the reproductive system that comprises the ovaries, uterus, placenta, pituitary gland, and hypothalamus. Vitamin D plays an important role in the female reproductive system[11]. For example, according to Parikh [17], vitamin D enhances the activity of aromatase and regulates sex hormone production from the ovaries and placenta through vitamin D receptors, thus participating in ovarian follicle formation. In animal studies, mice lacking VDR (vitamin D receptor) showed uterine hypoplasia and impaired folliculogenesis[8, 18]. Vitamin D also improving the oocyte and endometrial quality. It has been shown that vitamin D regulates the expression of the HOXA 10 gene in endometrial stromal cells and that this gene is crucial for endometrial development and embryonic implantation. Therefore, vitamin D levels appear to influence both endometrial receptivity as well as embryonic implantation [19, 20]. Vitamin D itself is involved in the regulation of calcium ion concentrations in the placenta and is critical in promoting endometrial decidualization [21].

A variety of studies indicate that vitamin D is closely related to reproductive system activities in PCOS. It was recently demonstrated that a low vitamin D level was present in many PCOS patients [9]. In PCOS patients, vitamin D deficiency exerts an adverse impact on sex hormone levels and thus interferes with the formation of the dominant follicle. A retrospective study [22] revealed explicitly that the serum vitamin D level in PCOS women was significantly lower than that in normal women and that a strong correlation existed between the two. A total of 639 women with PCOS were described by these studies, constituting the largest epidemiologic study conducted on PCOS to date. In our study, 82.5% of PCOS patients manifested vitamin D deficiency, with only two PCOS patients of the 200 patients showing normal vitamin D levels. Intriguingly, the incidence of vitamin D deficiency was also relatively high in normal healthy females at 37.5%. It is noteworthy that the mean vitamin D level was below the normal limit in both the PCOS patients and healthy women of child-bearing age, indicating that vitamin D deficiency is prevalent in women of child-bearing age in Beijing, particularly those with PCOS. In addition, our subjects were recruited over a time span of 1–1.5 years, which included all four seasons of the year; and we did not consider the potential influence of seasonal factors.

Recent studies have revealed [15, 23] that vitamin D levels are closely related to pregnancy outcomes in PCOS patients and that supplementation with vitamin D can improve one's fertility. Usadi et al.[24] demonstrated that raising the vitamin D level promoted successful ovulation induction, and these authors proposed vitamin D levels to be a potential predictor of reproductive success after induction. Vitamin D may exert its effect not only on the ovulation rate and sensitizing the ovary to letrozole but also improving the oocyte and endometrial quality. The abnormal oocyte and endometrial quality play an important role in the PCOS-related infertility[25, 26]. Rudick et al. [27] showed that subjects with serum 25 (OH) D3 sufficiencies exhibited a higher pregnancy rate than those with 25 (OH) D3 insufficiencies. The likely reason for this is that vitamin D influences pregnancy outcomes by affecting endometrial receptivity. A study [28] on in vitro fertilization among patients with PCOS-related infertility depicted an association between improved vitamin D levels and augmented pregnancy rates, with considerable significance attributed to normal vitamin D levels in pregnancy outcomes after in vitro fertilization. However, the underlying mechanism of vitamin D action in PCOS remains unknown. The pregnancy rate for PCOS patients was 48.32% after ovulation induction with letrozole, and the mean serum vitamin D level in the pregnant patients was 16.06 ng/mL, much higher than that in non-pregnant patients (13.54 ng/mL). When the subjects were stratified by vitamin D levels, we found that the pregnancy rate of vitamin D non-deficient subjects was significantly higher relative to that of vitamin D-deficient subjects. Therefore, mentioned data indicated that vitamin D levels were related to pregnancy rate after ovulation-induction therapy in PCOS, congruent with extant studies [24, 27]. According to our results, the mean vitamin D levels in both the pregnant and non-pregnant groups were significantly lower than the classical limit, and we therefore hypothesized that a higher pregnancy rate would be expected after elevating vitamin D to normal levels in PCOS patients.

We know of no therapeutic regimen centered around vitamin D supplementation for PCOS patients with vitamin D deficiency. However, according to the guidelines released by the American Association of Clinical Endocrinologists in 2011 on the Evaluation, Prevention, and Treatment of Vitamin D deficiency[29], two therapeutic regimens are currently recommended for all adults with vitamin D deficiency: one is supplementation with 50,000 units of vitamin D every week, once weekly for 8 weeks consecutively; the other is supplementation with 6000 units of vitamin D daily until the serum vitamin D level exceeds 30 ng/mL, followed by a daily maintenance dose of 1500–2000 units. It is also indicated in the guidelines that the tolerable upper limit for vitamin D in adults is 10,000 units daily and that excessive supplementation should be avoided.

There are several limitations in our study. Firstly, PCOS is the most common cause of anovulatory infertility; however, whether non-PCOS control and PCOS patients have the same reproductive potential is debatable. Then we didn’t compare the alterations in oocyte competence (OC) which are considered potential causative factors for subfertility in women with PCOS. Finally, although currently no intervention can be universally recommended to reverse endometrial dysfunction in PCOS women, lifestyle modifications and metformin may improve underlying endometrial dysfunction and pregnancy outcomes in obese and/or insulin resistant patients. Bariatric surgery has shown its efficacy in severely obese PCOS patients, but a careful evaluation of the benefit/risk ratio is warranted. Large scale randomized controlled clinical trials should address these possibilities.

In this study, we analyzed the relationship between Vitamin D level, PCOS infertility, and pregnancy outcome. The vitamin D deficiency were more generally found in our PCOS patients than those in healthy women of child-bearing age. We thus recommend that vitamin D testing be part of routine infertility examinations of PCOS patients. Moreover, according to the difference of vitamin D levels between PCOS patients who are pregnant and women who are not pregnant after ovulation-induction regimen, we suggest that Vitamin D supplementation may improve the success rate of ovulation induction pregnancy in PCOS infertile patients with vitamin D deficiency to some extent. Finally, additional high-quality, multi-center randomized controlled studies are needed to clarify the mechanism of vitamin D action in the reproductive endocrine function and pregnancy outcomes of PCOS patients, so as to shed light on potential adjuvant treatments for PCOS.

PCOS: Polycystic ovary syndrome; FSH: follicle-stimulating hormone; LH: luteinizing hormone; P: progesterone, E₂: estradiol, T: testosterone; and HCG: human chorionic gonadotropin

Ethics approval and consent to participate

The protocol was reviewed and approved by the ethics committee of the Beijing Anzhen Hospital. Informed consent was obtained from each participant prior to treatment.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no conflict of interest.

Author details

¹Department of Obstetrics and Gynecology, Beijing Anzhen Hospital，Capital Medical University. Beijing China; ² The Key Laboratory of Remodeling-Related R esearch center for cardiovascular diseases, Beijing 100029, China; and ³ Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Shandong First Medical University, Shandong 271000, China, ^#These authors contributed equally to this work.

Acknowledgements

We would like to thank the participating patients.

Authors’ contributions

C.P., J.L.: data extraction and analysis, drafting of the manuscript. Z.Z.: study design. K.W.: supervision, study design and revision of the manuscript. All authors have read and approved the final manuscript.

Funding

This study was supported by the National Natural Science Foundation of China (30973194), Clinical technology innovation project of Beijing Hospital Administration (XMLX201828) and the Basic and Clinical Cooperation Project of Capital Medical University (15JL05)

Availability of data and materials

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Al Wattar BH, Fisher M, Bevington L, Talaulikar V, Davies M, Conway G, et al. Clinical Practice Guidelines on the Diagnosis and Management of Polycystic Ovary Syndrome: A Systematic Review and Quality Assessment Study. J Clin Endocrinol Metab. 2021;106(8):2436–46.
Lizneva D, Suturina L, Walker W, Brakta S, Gavrilova-Jordan L, Azziz R. Criteria, prevalence, and phenotypes of polycystic ovary syndrome. Fertil Steril. 2016;106(1):6–15.
Huddleston HG, Dokras A. Diagnosis and Treatment of Polycystic Ovary Syndrome. JAMA. 2022;327(3):274–5.
Cooney LG, Dokras A. Cardiometabolic Risk in Polycystic Ovary Syndrome: Current Guidelines. Endocrinol Metab Clin North Am. 2021;50(1):83–95.
Escobar-Morreale HF. Polycystic ovary syndrome: definition, aetiology, diagnosis and treatment. Nat Rev Endocrinol. 2018;14(5):270–84.
Wikiera B, Zubkiewicz-Kucharska A, Nocon-Bohusz J, Noczynska A. Metabolic disorders in polycystic ovary syndrome. Pediatr Endocrinol Diabetes Metab. 2017;23(4):204–8.
Palomba S. Is fertility reduced in ovulatory women with polycystic ovary syndrome? An opinion paper. Hum Reprod. 2021;36(9):2421–8.
Voulgaris N, Papanastasiou L, Piaditis G, Angelousi A, Kaltsas G, Mastorakos G, et al. Vitamin D and aspects of female fertility. Horm (Athens). 2017;16(1):5–21.
He C, Lin Z, Robb SW, Ezeamama AE. Serum Vitamin D Levels and Polycystic Ovary syndrome: A Systematic Review and Meta-Analysis. Nutrients. 2015;7(6):4555–77.
Muscogiuri G, Altieri B, de Angelis C, Palomba S, Pivonello R, Colao A, et al. Shedding new light on female fertility: The role of vitamin D. Rev Endocr Metab Disord. 2017;18(3):273–83.
Lerchbaum E, Obermayer-Pietsch B. Vitamin D and fertility: a systematic review. Eur J Endocrinol. 2012;166(5):765–78.
Thomson RL, Spedding S, Buckley JD. Vitamin D in the aetiology and management of polycystic ovary syndrome. Clin Endocrinol (Oxf). 2012;77(3):343–50.
Cappy H, Giacobini P, Pigny P, Bruyneel A, Leroy-Billiard M, Dewailly D, et al. Low vitamin D3 and high anti-Mullerian hormone serum levels in the polycystic ovary syndrome (PCOS): Is there a link? Ann Endocrinol (Paris). 2016;77(5):593–9.
Ngo DT, Chan WP, Rajendran S, Heresztyn T, Amarasekera A, Sverdlov AL, et al. Determinants of insulin responsiveness in young women: Impact of polycystic ovarian syndrome, nitric oxide, and vitamin D. Nitric Oxide. 2011;25(3):326–30.
Trummer C, Pilz S, Schwetz V, Obermayer-Pietsch B, Lerchbaum E. Vitamin D. PCOS and androgens in men: a systematic review. Endocr Connect. 2018;7(3):R95–113.
Michigami T. [Update on recent progress in vitamin D research. Vitamin D Metabolism and Its Regulation.]. Clin Calcium. 2017;27(11):1517–23.
Parikh G, Varadinova M, Suwandhi P, Araki T, Rosenwaks Z, Poretsky L, et al. Vitamin D regulates steroidogenesis and insulin-like growth factor binding protein-1 (IGFBP-1) production in human ovarian cells. Horm Metab Res. 2010;42(10):754–7.
Yoshizawa T, Handa Y, Uematsu Y, Takeda S, Sekine K, Yoshihara Y, et al. Mice lacking the vitamin D receptor exhibit impaired bone formation, uterine hypoplasia and growth retardation after weaning. Nat Genet. 1997;16(4):391–6.
Agic A, Xu H, Altgassen C, Noack F, Wolfler MM, Diedrich K, et al. Relative expression of 1,25-dihydroxyvitamin D3 receptor, vitamin D 1 alpha-hydroxylase, vitamin D 24-hydroxylase, and vitamin D 25-hydroxylase in endometriosis and gynecologic cancers. Reprod Sci. 2007;14(5):486–97.
Bagot CN, Troy PJ, Taylor HS. Alteration of maternal Hoxa10 expression by in vivo gene transfection affects implantation. Gene Ther. 2000;7(16):1378–84.
Shahrokhi SZ, Ghaffari F, Kazerouni F. Role of vitamin D in female reproduction. Clin Chim Acta. 2016;455:33–8.
Krul-Poel YH, Snackey C, Louwers Y, Lips P, Lambalk CB, Laven JS, et al. The role of vitamin D in metabolic disturbances in polycystic ovary syndrome: a systematic review. Eur J Endocrinol. 2013;169(6):853–65.
Fung JL, Hartman TJ, Schleicher RL, Goldman MB. Association of vitamin D intake and serum levels with fertility: results from the Lifestyle and Fertility Study. Fertil Steril. 2017;108(2):302–11.
Usadi RS, Legro RS. Reproductive impact of polycystic ovary syndrome. Curr Opin Endocrinol Diabetes Obes. 2012;19(6):505–11.
Palomba S, Piltonen TT, Giudice LC. Endometrial function in women with polycystic ovary syndrome: a comprehensive review. Hum Reprod Update. 2021;27(3):584–618.
Palomba S, Daolio J, La Sala GB. Oocyte Competence in Women with Polycystic Ovary Syndrome. Trends Endocrinol Metab. 2017;28(3):186–98.
Rudick BJ, Ingles SA, Chung K, Stanczyk FZ, Paulson RJ, Bendikson KA. Influence of vitamin D levels on in vitro fertilization outcomes in donor-recipient cycles. Fertil Steril. 2014;101(2):447–52.
Zhao J, Liu S, Wang Y, Wang P, Qu D, Liu M, et al. Vitamin D improves in-vitro fertilization outcomes in infertile women with polycystic ovary syndrome and insulin resistance. Minerva Med. 2019;110(3):199–208.
Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, et al. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011;96(7):1911–30.

No competing interests reported.

Download PDF

Version 2

posted

You are reading this latest preprint version

Association between Vitamin D and pregnancy in women with polycystic ovary syndrome: a case-control study from Beijing, China

Status:

Version 2

Abstract

Background

Methods

Results

Conclusions

Introduction

Materials And Methods

Study population

Patient treatment

Statistical analysis

Results

Comparison of serum 25-(OH) D3 levels between the experimental and control groups

Pregnancy outcomes after ovulation induction in the experimental group

Comparison of serum 25-(OH) D3 levels between the pregnant and non-pregnant groups

Comparison of pregnancy rates between subjects with different vitamin D levels

Discussion

CONCLUSION

Abbreviations

Declarations

References

Additional Declarations

Status:

Version 2