Skip to main content
Download PDF

Association of ADAMTS proteoglycanases downregulation with IVF-ET outcomes in patients with polycystic ovary syndrome: a systematic review and meta-analysis

Reproductive Biology and Endocrinology volume 20, Article number: 169 (2022) Cite this article

Abstract

Background

A disintegrin and metalloproteinase with thrombospondin-like motifs (ADAMTS) is involved in inflammation and fertility in women with polycystic ovary syndrome (PCOS). This study aims to assess the role of ADAMTS level in the outcomes of in vitro fertilization and embryo transfer (IVF-ET) in women with PCOS, using a meta-analytic approach.

Methods

We systematically searched Web of Science, PubMed, EmBase, and the Cochrane library to identify potentially eligible studies from inception until December 2021. Study assess the role of ADAMTS levels in patients with PCOS was eligible in this study. The pooled effect estimates for the association between ADAMTS level and IVF-ET outcomes were calculated using the random-effects model.

Results

Five studies involving a total of 181 patients, were selected for final analysis. We noted that ADAMTS-1 levels were positively correlated to oocyte maturity (r = 0.67; P = 0.004), oocyte recovery (r = 0.74; P = 0.006), and fertilization (r = 0.46; P = 0.041) rates. Moreover, ADAMTS-4 levels were positively correlated to oocyte recovery (r = 0.91; P = 0.001), and fertilization (r = 0.85; P = 0.017) rates. Furthermore, downregulation of ADAMTS-1, ADAMTS-4, ADAMTS-5, and ADAMTS-9 was associated with elevated follicle puncture (ADAMTS-1: weighted mean difference [WMD], 7.24, P < 0.001; ADAMTS-4: WMD, 7.20, P < 0.001; ADAMTS-5: WMD, 7.20, P < 0.001; ADAMTS-9: WMD, 6.38, P < 0.001), oocytes retrieval (ADAMTS-1: WMD, 1.61, P < 0.001; ADAMTS-4: WMD, 3.63, P = 0.004; ADAMTS-5: WMD, 3.63, P = 0.004; ADAMTS-9: WMD, 3.20, P = 0.006), and Germinal vesicle oocytes levels (ADAMTS-1: WMD, 2.89, P < 0.001; ADAMTS-4: WMD, 2.19, P < 0.001; ADAMTS-5: WMD, 2.19, P < 0.001; ADAMTS-9: WMD, 2.89, P < 0.001). Finally, the oocytes recovery rate, oocyte maturity rate, fertilization rate, cleavage rate, good-quality embryos rate, blastocyst formation rate, and clinical pregnancy rate were not affected by the downregulation of ADAMTS-1, ADAMTS-4, ADAMTS-5, and ADAMTS-9 (P > 0.05).

Conclusions

This study found that the outcomes of IVF-EF in patients with PCOS could be affected by ADAMTS-1 and ADAMTS-4; further large-scale prospective studies should be performed to verify these results.

Background

Polycystic ovary syndrome (PCOS), the most common endocrine disorder among women of reproductive age, is characterized by hyperandrogenemia, hirsutism, acne, oligo-or anovulation, and polycystic ovaries [1]. The prevalence of PCOS in women of reproductive age ranges from 10 to 16% [2, 3], and it is significantly associated with infertility, obesity, insulin resistance, type 2 diabetes, dyslipidemia, cardiovascular disease, hepatic steatosis, and endometrial cancer [4,5,6]. The hyperresponsiveness to stimulation by luteinizing hormone and failed downregulation of thecal androgen production associated with functional ovarian hyperandrogenism, might play an important role in the pathophysiology of PCOS [7, 8]. Moreover, the insulin resistance-induced hyperinsulinemia augments the luteinizing hormone-induced homologous desensitization, thereby aggravating hyperandrogenism [9, 10]. Furthermore, follicle maturation arrest and anovulation could be caused by hyperinsulinemia, which synergizes with androgen to prematurely luteinize granulosa cells [11].

Several studies have already addressed the prognosis of PCOS [12,13,14]. A systematic review and found PCOS were associated with an increased risk of pregnancy-induced hypertension, pre-eclampsia, gestational diabetes and premature delivery [12]. Moreover, they point out the alteration of oocyte competence contributed an important role on subfertility for patients with PCOS [13]. Furthermore, PCOS could affect endometrium, chronic low-grade inflammation, immune dysfunction, altered uterine vascularity, abnormal endometrial gene expression and cellular abnormalities [14]. Therefore, additional potential markers for the prognosis of PCOS should be explored for the purpose of improving the prognosis of PCOS.

Several members of the a disintegrin and metalloproteinase with thrombospondin-like motifs (ADAMTS) family have been identified in growing follicles during ovulation and in the corpora lutea of several mammalian species [15,16,17,18,19,20,21,22,23]. These findings indicate that the members at the proteoglycanase arm of the ADAMTS family were the most expressed. However, the expression of all members of the ADAMTS family during folliculogenesis, was not systematically explored. No systematic review or meta-analysis have been conducted to assess the role of ADAMTS levels in the outcome of IVF-ET in patients with PCOS. Therefore, this study was performed to assess the potential role of members of the ADAMTS family in IVF-ET outcomes in women with PCOS.

Methods

Data sources, search strategy, and selection criteria

The protocol of this systematic review and meta-analysis was registered at INPLASY (ID: INPLASY202260115). The revised Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) Statement was applied to conduct and report this systematic review and meta-analysis [24]. Published articles assessing the role of ADAMTS levels in patients with PCOS, were considered eligible for this study, and all eligible articles, regardless of the language used for publication and the publication status, were included. Three databases (Web of Science, PubMed, and EmBase) and the Cochrane library, were systematically searched from their year of inception until December 2021, using the following search terms: “Polycystic ovary syndrome” [Mesh] or “polycystic ovary syndrome” or “PCOS” and “ADAMTS Protein” [Mesh] or “ADAMTS” or “Aggrecanase-1” or “A Disintegrin And Metalloproteinase With Thrombospondin Motifs”. We also reviewed the reference lists of retrieved studies to identify any new eligible study.

The process of literature search and study selection was independently performed by 2 reviewers, and conflicts between these reviewers were settled by group discussion. The inclusion criteria were as follows: (1) Patients: all patients diagnosed with PCOS; (2) Exposure: members of the ADAMTS family, including ADAMTS-1, ADAMTS-4, ADAMTS-5, ADAMTS-9, ADAMTS-19; (3) Comparison: ADAMTS level; (4) Outcomes: implantation, follicles punctured, oocytes retrieved, metaphase II oocytes, germinal vesicle oocytes, and oocyte recovery, oocyte maturity, fertilization, cleavage, good-quality embryo, blastocyst formation, and clinical pregnancy rates; and (5) Study design: no restrictions were placed on study design.

Data collection and quality assessment

Two reviewers independently performed data abstraction and quality assessment, and disagreement between these reviewers was resolved by a third reviewer, after referring to the full text of the original article. The following information were collected from included studies: first author’s name, publication year, study design, country, sample size, mean age, body mass index (BMI), reported ADAMTS family members, and reported outcomes. The quality of observational studies was assessed using the Newcastle–Ottawa Scale (NOS), and the staring system for each study ranged from 0–9 [25].

Statistical analysis

The associations of ADAMTS proteoglycanases level with IVF-ET outcomes in PCOS were assigned Spearman coefficients, and the pooled effect estimates were calculated using the random-effects model, which considered the underlying differences across included studies [26, 27]. The heterogeneity among included studies was assessed using I2 and Q statistics, and I2 > 50.0% or P < 0.10 was considered significant heterogeneity [28, 29]. The robustness of pooled conclusions was assessed using a sensitivity analysis through sequential removal of individual studies [30]. All reported P values for pooled results are 2-sided, and P < 0.05 was considered statistically significant. All statistical analysis in our study was performed using STATA software (version 10.0; Stata Corporation, College Station, TX, USA).

Results

Literature search

A total of 186 articles were identified from initial electronic searches, and 113 were retained after duplicate articles were removed. Then 84 studies were removed for having irrelevant titles or abstracts. The remaining 29 studies were selected for full-text evaluations and 24 were excluded because of Review (n = 3), insufficient data (n = 17), and other diseases (n = 4). The details of the literature search and study selection are shown in Fig. 1, and a total of 5 studies were included in the final quantitative analysis [31,32,33,34,35].

Fig. 1
figure 1

The PRISMA flowchart for the process of literature search and study selection

Full size image

Study characteristics

The baseline characteristics of the included studies and recruited patients are shown in Table 1. Of the 5 studies included, 3 were prospective and 2 were retrospective. One study was conducted in Turkey, 2 were conducted in Iran, and 2 were conducted in China. The mean age of included patients ranged from 28.6 to 30.5 years, while the mean BMI across included studies ranged from 22.7 to 27.9 kg/m2. Four studies reported on the role of ADAMTS-1, 1 reported on the role of ADAMTS-4, 1 reported on the role of ADAMTS-5, and 1 reported on the role of ADAMTS-9.

Table 1 The baseline characteristics of identified studies and recruited patients
Full size table

Quality of included studies

Table 2 summarizes the methodological quality of the included studies, and all 5 studies were of high quality (7 or more stars); 3 studies had 8 stars and 2 had 7 stars.

Table 2 The Newcastle–Ottawa Scale of individual study
Full size table

Qualitative analysis

A study performed by Xiao et al., found that ADAMTS-1 level was positively correlated with the rates of oocyte maturity, oocyte recovery, and fertilization (r = 0.8313; P = 0.0403); the relationship between ADAMTS-1 levels and the rates of cleavage and good quality embryo, was not statistically significant [31]. Tola et al., found no significant association between ADAMTS-1 levels and metaphase II oocytes; however, ADAMTS-1 levels were positively correlated to implantation (data not shown) [32]. GohariTaban et al., found that ADAMTS-1 levels were positively correlated to oocyte recovery, oocyte maturation, and fertilization rates. Moreover, they pointed out that ADAMTS-9 levels were significantly correlated to oocyte recovery and oocyte maturation rates, while the relationship between ADAMTS-9 level and fertilization rate was not statistically significant [33]. GohariTaban et al., also found that ADAMTS-4 levels were positively correlated to oocyte recovery, oocyte maturation, and fertilization rates. Furthermore, there were significant associations between ADAMTS-5 level and oocyte recovery, oocyte maturation, and fertilization rates [34]. Yang et al., found that ADAMTS-1 levels were positively correlated to oocyte maturation and good-quality embryo rates; ADAMTS-1 levels were not associated with fertilization, cleavage, and blastocyst formation rates [35].

Pooled Spearman coefficients

We noted that ADAMTS-1 levels were positively correlated to oocyte maturity rate (r = 0.67; P = 0.004; without evidence of heterogeneity), while ADAMTS-4 (r = 0.60; P = 0.221), ADAMTS-5 (r = 0.66; P = 0.164), and ADAMTS-9 (r = 0.32; P = 0.493) levels were not (Fig. 2). Moreover, our results indicate that ADAMTS-1 (r = 0.74; P = 0.006) and ADAMTS-4 (r = 0.91; P = 0.001) levels were positively correlated to oocyte recovery rate, while ADAMTS-5 (r = 0.54; P = 0.279) and ADAMTS-9 (r = 0.78; P = 0.060) levels were not (Fig. 3). Similarly, ADAMTS-1 (r = 0.46; P = 0.041) and ADAMTS-4 (r = 0.85; P = 0.017) levels were significantly correlated to fertilization rate, while ADAMTS-5 (r = 0.52; P = 0.298) and ADAMTS-9 (r = 0.38; P = 0.434) levels were not (Fig. 4). Finally, the level of ADAMTS-1 was not associated with cleavage (r = 0.35; P = 0.308), good quality embryo (r = 0.36; P = 0.290), and blastocyst formation (r = 0.07; P = 0.788) rates (Fig. 5).

Fig. 2
figure 2

The relationship between ADAMTS family members and oocyte maturity rate

Full size image
Fig. 3
figure 3

The relationship between ADAMTS family members and oocyte recovery rate

Full size image
Fig. 4
figure 4

The relationship between ADAMTS family members and fertilization rate

Full size image
Fig. 5
figure 5

The relationship between ADAMTS-1 levels and cleavage, good-quality embryo, and blastocyst formation rates

Full size image

Downregulation of ADAMTS family members and IVF-ET outcomes

A summary of the effects of downregulation of ADAMTS family members on IVF-ET outcomes is shown in Table 3. We noted that downregulation of ADAMTS-1, ADAMTS-4, ADAMTS-5, and ADAMTS-9 was associated with a large number of punctured follicles, retrieved, and Germinal vesicle oocytes, but did not affect Metaphase II oocytes and oocytes recovery, oocyte maturity, and fertilization rates. Moreover, ADAMTS-1 downregulation was not associated with cleavage, good-quality embryo, clinical pregnancy, and blastocyst formation rates.

Table 3 The pooled results for ADAMTS family members downregulation and IVF-ET Outcomes
Full size table

Discussion

This study is the first to assess the role of ADAMTS family members in the outcomes of IVF-ET for patients with PCOS, using the meta-analytic approach. A total of 181 patients with PCOS from 5 studies were included, along with a wide range of patient characteristics. This study found that the oocyte maturity, oocyte recovery, and fertilization rates, were affected by ADAMTS-1 levels. Moreover, ADAMTS-4 levels were positively correlated to oocyte recovery and fertilization rates. Finally, the downregulation of ADAMTS-1, ADAMTS-4, ADAMTS-5, and ADAMTS-9 was associated with elevated follicle puncture, oocytes retrieval, and Germinal vesicle oocytes levels.

The methodology of included studies was systematically assessed, and all included studies were of high quality. The cutoff value of the ADAMTS family members in patients with PCOS varied across the included studies, while could affect the net effect estimates for the role of ADAMTS family members. Moreover, 2 of the included studies absent the representativeness of the cohort, and several members of the ADAMTS family were obtained from only a few of the included studies; therefore, the results are not reliable. Therefore, the results of this study should be cautiously applied as they require verification by further large-scale prospective studies.

We noted that ADAMTS-1 levels were positively correlated to oocyte maturity, oocyte recovery, and fertilization rates and that downregulation of ADAMTS-1 was significantly correlated to elevated follicle puncture, oocytes retrieval, and Germinal vesicle oocytes levels. A possible reason for this could be the ADAMTS-1 mainly expressed in the granulosa cells of mammalian preovulatory follicles, which could induced by LH through transactivation of the PG receptor, and suggested ADAMTS-1 play an important role in ovulation and folliculogenesis [17, 19, 36]. Moreover, ADAMTS-1 modulates cell signaling and could affect the sequestration of signaling factors within the cumulus/oocyte microenvironment by physical or oxidative stress through versican cleavage; this could be useful in predicting oocyte capacity and subsequent pregnancy [37,38,39].

This study found the oocyte recovery and fertilization rates to be significantly correlated to ADAMTS-4 levels, and ADAMTS-4 downregulation to be significantly correlated to elevated follicle puncture, oocytes retrieval, and Germinal vesicle oocytes levels. Moreover, the follicle puncture, oocytes retrieval, and Germinal vesicle oocytes levels were affected by ADAMTS-5, and ADAMTS-9 downregulation. ADAMTS-1, ADAMTS-4, and ADAMTS-5 have overlapping effects on aggrecan, versican, and brevican degradation [40]. Altered levels of ADAMTS-1, ADAMTS-4, and ADAMTS-5 could affect the main component of the cumulus-oocyte complex, and the cumulus cells gene expression was regarded as a most promising oocyte quality marker [32, 41, 42]. Moreover, ADAMTS-9 is involved in extracellular matrix binding and expression during embryogenesis, and ADAMTS-9 downregulation in the cumulus cells is significantly correlated to oocytes maturation arrest [43, 44].

Although ADAMTS-1 levels were positively correlated to oocyte maturity, oocyte recovery, and fertilization rates, ADAMTS-4 levels were only positively correlated to oocyte recovery and fertilization rates. The downregulation of ADAMTS-1 and ADAMTS-4 was not associated with the oocyte recovery, oocyte maturity, fertilization, cleavage, good-quality embryo, clinical pregnancy, and blastocyst formation rates. The possible reason for this could be the small number of studies that reported these outcomes, and the power might not be enough to detect the potential role of ADAMTS family members in IVF-ET outcomes.

Owing to the PCOS could affect oocyte competence and endometrial function, and causing series pregnancy complications [12,13,14], the prognostic factor for IVF-ET outcomes in patients with PCOS should be explored. This study found IVF-EF outcomes could be affected by ADAMTS-1 and ADAMTS-4 in patients with PCOS. Therefore, the ADAMTS for PCOS patients should be screened for patients at high risk, then the intervention should be performed to improve further IVF-ET outcomes.

This study has several limitations: (1) the analysis included both prospective and retrospective studies, and there could be selection and recall biases; (2) the background therapies for PCOS varied across the included studies; this could affect the role of ADAMTS family members; (3) the role of ADAMTS-4, ADAMTS-5, and ADAMTS-9 in IVF-ET outcomes was discussed in just a few studies, and several other outcomes were not investigated, such as implantation, abortion, miscarriage, and repeat implantation failure; (4) the relationship between ADAMTS family members and IVF-ET outcomes based on univariate regression, and the characteristics of patients, were not adjusted; (5) subgroup analysis were not performed owing to smaller number of included studies; and (6) inherent limitations of meta-analysis in the published articles, including restricted detailed analyses and inevitable publication bias.

Conclusions

Our study found that ADAMTS-1 levels were positively correlated to oocyte maturity, oocyte recovery, and fertilization rates, while ADAMTS-4 levels were positively correlated to oocyte maturity, oocyte recovery, and fertilization rates. Moreover, the downregulation of ADAMTS-1, ADAMTS-4, ADAMTS-5, and ADAMTS-9 was significantly correlated to elevated follicle puncture, oocytes retrieval, and Germinal vesicle oocytes levels. Further large-scale prospective studies should be conducted to verify the results of this study and compare the role of ADAMTS downregulation on implantation, abortion, miscarriage, repeat implantation failure.

Availability of data and materials

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

Abbreviations

ADAMTS:

A disintegrin and metalloproteinase with thrombospondin- like motifs

BMI:

Body mass index

IVF-ET:

In vitro fertilization and embryo transfer

NOS:

Newcastle–Ottawa Scale

PCOS:

Polycystic ovary syndrome

PRISMA:

Preferred reporting items for systematic reviews and meta-analysis

References

  1. Cai X, Qiu S, Li L, et al. Circulating irisin in patients with polycystic ovary syndrome: a meta-analysis. Reprod Biomed Online. 2018;36:172–80.

    Article  CAS  Google Scholar 

  2. McCartney CR, Marshall JC. Polycystic ovary syndrome. N Engl J Med. 2016;375:54–64.

    Article  Google Scholar 

  3. Lauritsen MP, Bentzen JG, Pinborg A, et al. The prevalence of polycystic ovary syndrome in a normal population according to the Rotterdam criteria versus revised criteria including anti-Mullerian hormone. Hum Reprod. 2014;29:791–801.

    Article  CAS  Google Scholar 

  4. Martini AE, Healy MW. Polycystic Ovarian Syndrome: Impact on Adult and Fetal Health. Clin Obstet Gynecol. 2021;64:26–32.

    Article  Google Scholar 

  5. Su NJ, Huang CY, Liu J, et al. Association between baseline LH/FSH and live-birth rate after fresh-embryo transfer in polycystic ovary syndrome women. Sci Rep. 2021;11:20490.

    Article  CAS  Google Scholar 

  6. Diamanti-Kandarakis E, Piperi C, Argyrakopoulou G, et al. Polycystic ovary syndrome: the influence of environmental and genetic factors. Hormones (Athens). 2006;5:17–34.

    Article  Google Scholar 

  7. Huang J, Chen P, Xiang Y, et al. Gut microbiota dysbiosis-derived macrophage pyroptosis causes polycystic ovary syndrome via steroidogenesis disturbance and apoptosis of granulosa cells. Int Immunopharmacol. 2022;107: 108717.

    Article  CAS  Google Scholar 

  8. Huang-Doran I, Kinzer AB, Jimenez-Linan M, et al. Ovarian Hyperandrogenism and Response to Gonadotropin-releasing Hormone Analogues in Primary Severe Insulin Resistance. J Clin Endocrinol Metab. 2021;106:2367–83.

    Article  Google Scholar 

  9. Gleicher N, Darmon SK, Molinari E, et al. Importance of IGF-I levels in IVF: potential relevance for growth hormone (GH) supplementation. J Assist Reprod Genet. 2022;39:409–16.

    Article  Google Scholar 

  10. Zhang Y, Ouyang X, You S, et al. Effect of human amniotic epithelial cells on ovarian function, fertility and ovarian reserve in primary ovarian insufficiency rats and analysis of underlying mechanisms by mRNA sequencing. Am J Transl Res. 2020;12:3234–54.

    CAS  Google Scholar 

  11. Rosenfield RL, Ehrmann DA. The Pathogenesis of Polycystic Ovary Syndrome (PCOS): The hypothesis of PCOS as functional ovarian hyperandrogenism revisited. Endocr Rev. 2016;37:467–520.

    Article  CAS  Google Scholar 

  12. Palomba S, de Wilde MA, Falbo A, et al. Pregnancy complications in women with polycystic ovary syndrome. Hum Reprod Update. 2015;21:575–92.

    Article  Google Scholar 

  13. Palomba S, Daolio J, La Sala GB. Oocyte competence in women with polycystic ovary syndrome. Trends Endocrinol Metab. 2017;28:186–98.

    Article  CAS  Google Scholar 

  14. Palomba S, Piltonen TT, Giudice LC. Endometrial function in women with polycystic ovary syndrome: a comprehensive review. Hum Reprod Update. 2021;27:584–618.

    Article  CAS  Google Scholar 

  15. Rosewell KL, Al-Alem L, Zakerkish F, McCord L, Akin JW, Chaffin CL, Brännström M, Curry TE Jr. Induction of proteinases in the human preovulatory follicle of the menstrual cycle by human chorionic gonadotropin. Fertil Steril. 2015;103:826–33.

    Article  CAS  Google Scholar 

  16. Robker RL, Russell DL, Espey LL, et al. Progesterone-regulated genes in the ovulation process: ADAMTS-1 and cathepsin L proteases. Proc Natl Acad Sci U S A. 2000;97:4689–94.

    Article  CAS  Google Scholar 

  17. Doyle KM, Russell DL, Sriraman V, et al. Coordinate transcription of the ADAMTS-1 gene by luteinizing hormone and progesterone receptor. Mol Endocrinol. 2004;18:2463–78.

    Article  CAS  Google Scholar 

  18. Madan P, Bridges PJ, Komar CM, et al. Expression of messenger RNA for ADAMTS subtypes changes in the periovulatory follicle after the gonadotropin surge and during luteal development and regression in cattle. Biol Reprod. 2003;69:1506–14.

    Article  CAS  Google Scholar 

  19. Boerboom D, Russell DL, Richards JS, et al. Regulation of transcripts encoding ADAMTS-1 (a disintegrin and metalloproteinase with thrombospondin-like motifs-1) and progesterone receptor by human chorionic gonadotropin in equine preovulatory follicles. J Mol Endocrinol. 2003;31:473–85.

    Article  CAS  Google Scholar 

  20. Shimada M, Nishibori M, Yamashita Y, et al. Down-regulated expression of A disintegrin and metalloproteinase with thrombospondin-like repeats-1 by progesterone receptor antagonist is associated with impaired expansion of porcine cumulus-oocyte complexes. Endocrinology. 2004;145:4603–14.

    Article  CAS  Google Scholar 

  21. Peluffo MC, Murphy MJ, Baughman ST, et al. Systematic analysis of protease gene expression in the rhesus macaque ovulatory follicle: metalloproteinase involvement in follicle rupture. Endocrinology. 2011;152:3963–74.

    Article  CAS  Google Scholar 

  22. Freimann S, Ben-Ami I, Dantes A, et al. Differential expression of genes coding for EGF-like factors and ADAMTS1 following gonadotropin stimulation in normal and transformed human granulosa cells. Biochem Biophys Res Commun. 2005;333:935–43.

    Article  CAS  Google Scholar 

  23. Richards JS, Hernandez-Gonzalez I, Gonzalez-Robayna I, et al. Regulated expression of ADAMTS family members in follicles and cumulus oocyte complexes: evidence for specific and redundant patterns during ovulation. Biol Reprod. 2005;72:1241–55.

    Article  CAS  Google Scholar 

  24. Page MJ, McKenzie JE, Bossuyt PM, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372: n71.

    Article  Google Scholar 

  25. Wells G, Shea B, O’Connell D. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. Ottawa (ON): Ottawa Hospital Research Institute 2009. Available: http://www.ohri.ca/programs/clinical_epidemiology/oxford.htm.

  26. DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7:177–88.

    Article  CAS  Google Scholar 

  27. Ades AE, Lu G, Higgins JP. The interpretation of random-effects metaanalysis in decision models. Med Decis Making. 2005;25:646–54.

    Article  CAS  Google Scholar 

  28. Deeks JJ, Higgins JPT, Altman DG. Analyzing data and undertaking meta-analyses. In: Higgins J, Green S, editors. Cochrane Handbook for Systematic Reviews of Interventions 5.0.1. Oxford, UK: The Cochrane Collaboration; 2008.

    Google Scholar 

  29. Higgins JPT, Thompson SG, Deeks JJ, et al. Measuring inconsistency in meta-analyses. BMJ. 2003;327:557–60.

    Article  Google Scholar 

  30. Tobias A. Assessing the influence of a single study in meta-analysis. Stata Tech Bull. 1999;47:15–7.

    Google Scholar 

  31. Xiao S, Li Y, Li T, et al. Evidence for decreased expression of ADAMTS-1 associated with impaired oocyte quality in PCOS patients. J Clin Endocrinol Metab. 2014;99:E1015–21.

    Article  CAS  Google Scholar 

  32. Tola EN, Karatopuk DU, Koroglu N, et al. Follicular ADAMTS-1 and aggrecan levels in polycystic ovary syndrome. J Assist Reprod Genet. 2017;34:811–6.

    Article  Google Scholar 

  33. GohariTaban S, Amiri I, Soleimani Asl S, et al. Abnormal expressions of ADAMTS-1, ADAMTS-9 and progesterone receptors are associated with lower oocyte maturation in women with polycystic ovary syndrome. Arch Gynecol Obstet. 2019;299:277–86.

    Article  CAS  Google Scholar 

  34. Gohari Taban S, Amiri I, Saidijam M, et al. ADAMTS proteoglycanases downregulation with impaired oocyte quality in PCOS. Arch Endocrinol Metab. 2021;2359:3997000000321.

    Google Scholar 

  35. Yang G, Yao G, Xu Z, et al. Expression Level of ADAMTS1 in Granulosa Cells of PCOS Patients Is Related to Granulosa Cell Function, Oocyte Quality, and Embryo Development. Front Cell Dev Biol. 2021;9: 647522.

    Article  Google Scholar 

  36. Brown HM, Dunning KR, Robker RL, et al. Requirement for ADAMTS-1 in extracellular matrix remodeling during ovarian folliculogenesis and lymphangiogenesis. Dev Biol. 2006;300:699–709.

    Article  CAS  Google Scholar 

  37. Wu Y, Wu J, Lee DY, et al. Versican protects cells from oxidative stress-induced apoptosis. Matrix Biol. 2005;24:3–13.

    Article  CAS  Google Scholar 

  38. Wathlet S, Adriaenssens T, Segers I, et al. Cumulus cell gene expression predicts better cleavage-stage embryo or blastocyst development and pregnancy for ICSI patients. Hum Reprod. 2011;26:1035–51.

    Article  CAS  Google Scholar 

  39. Adriaenssens T, Wathlet S, Segers I, et al. Cumulus cell gene expression is associated with oocyte developmental quality and influenced by patient and treatment characteristics. Hum Reprod. 2010;25:1259–70.

    Article  CAS  Google Scholar 

  40. Demircan K, Topcu V, Takigawa T, et al. ADAMTS4 and ADAMTS5 knockout mice are protected from versican but not aggrecan or brevican proteolysis during spinal cord injury. Biomed Res Int. 2014;2014: 693746.

    Article  Google Scholar 

  41. Wathlet S, Adriaenssens T, Segers I, et al. New candidate genes to predict pregnancy outcome in single embryo transfer cycles when using cumulus cell gene expression. Fertil Steril. 2012;98:432–9.

    Article  CAS  Google Scholar 

  42. Gebhardt KM, Feil DK, Dunning KR, et al. Human cumulus cell gene expression as a biomarker of pregnancy outcome after single embryo transfer. Fertil Steril. 2011;96:47–52.

    Article  CAS  Google Scholar 

  43. Tang H, Liu Y, Li J, et al. Gene knockout of nuclear progesterone receptor provides insights into the regulation of ovulation by LH signaling in zebrafish. Sci Rep. 2016;6:28545.

    Article  Google Scholar 

  44. Guzman L, Adriaenssens T, Ortega-Hrepich C, et al. Human antral follicles <6 mm: a comparison between in vivo maturation and in vitro maturation in non-hCG primed cycles using cumulus cell gene expression. Mol Hum Reprod. 2013;19:7–16.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

There was no acknowledgement.

Funding

No specific financial or non-financial support was received for the review.

Author information

Authors and Affiliations

  1. School of Public Health, China Medical University, Shenyang, China

    Yanbin Shi & Hongbo Liu

  2. Reproductive and Genetic Medicine Center, Dalian Women and Children’s Medical Center, Dalian, China

    Yanbin Shi, Yang Shi, Guiyuan He, Guang Wang & Xiaoguang Shao

Authors
  1. Yanbin Shi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yang Shi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Guiyuan He
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Guang Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hongbo Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Xiaoguang Shao
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

SYB: study design, data collection and analysis, writing and revision of the manuscript; SY: data collection and analysis; HGY: data collection and analysis; WG: data collection and analysis; LHB: revision of the manuscript; SXG: revision of the manuscript. The author(s) read and approved the final manuscript.

Corresponding authors

Correspondence to Hongbo Liu or Xiaoguang Shao.

Ethics declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

All authors declare no competing interest.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Shi, Y., Shi, Y., He, G. et al. Association of ADAMTS proteoglycanases downregulation with IVF-ET outcomes in patients with polycystic ovary syndrome: a systematic review and meta-analysis. Reprod Biol Endocrinol 20, 169 (2022). https://doi.org/10.1186/s12958-022-01035-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/s12958-022-01035-9

Reproductive Biology and Endocrinology

ISSN: 1477-7827

Contact us