卵泡液中邻苯二甲酸盐代谢物对接受卵胞浆内单精子注射的印度妇女卵巢储备和卵巢功能的影响。

Firuza Rajesh Parikh M.D., Ph.D. , Shonali Uttamchandani B.Sc. , Sujatha Sawkar M.D. , Madhavi Panpalia M.S. , Nandkishor Naik B.Sc. , Prachi Sinkar M.D. , Dhananjaya Kulkarni Ph.D. , Rajesh Parikh M.D.
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To evaluate the effects of follicular phthalate metabolites on peak serum estradiol (E</span></span><sub>2</sub>) levels and the total number of oocytes and mature metaphase II (MII) stage oocytes retrieved to assess the impact of phthalate toxicity on ovarian function.</p></div><div><h3>Design</h3><p><span>A subanalysis of an ongoing prospective cohort study was conducted to examine the association between the levels of six phthalate metabolites, namely, mono-n-butyl phthalate (MBP), mono-ethyl phthalate (MEP), mono-isononyl phthalate (MiNP), mono-isodecyl phthalate (MiDP), mono(2-ethyl-5-oxohexyl) phthalate, and mono(2-ethyl-5-hydroxyhexyl) phthalate, in the FF of Indian women undergoing ICSI and their ovarian reserve markers (AFC and serum AMH levels). To investigate the association of these follicular phthalate metabolite levels with the peak E</span><sub>2</sub> levels and the total number of oocytes and number of MII stage oocytes retrieved.</p></div><div><h3>Setting</h3><p>In vitro fertilization center in a referral hospital in India.</p></div><div><h3>Patient(s)</h3><p>A total of 245 consenting Indian women who had undergone oocyte retrieval<span> between April 2017 and mid-March 2020 were included. Each woman contributed one FF sample to the study. This was screened for six phthalate metabolites. The samples were collected before the coronavirus disease 2019 pandemic.</span></p></div><div><h3>Intervention(s)</h3><p><span>Using liquid chromatography-tandem mass spectrometry, the total levels of six phthalate metabolites were quantified in the FF of 245 women. Using linear regression<span> models that were unadjusted and adjusted for maternal age and body mass index (BMI), we evaluated the association between the follicular metabolites in these women and their AFC, serum AMH levels, peak E</span></span><sub>2</sub> levels, total number of oocytes, and MII stage oocytes.</p></div><div><h3>Main Outcome Measure(s)</h3><p>To evaluate the impact of phthalate-induced ovarian toxicity on the ovarian reserve and ovarian function in Indian women undergoing ICSI by studying their accumulated levels in their FF.</p></div><div><h3>Result(s)</h3><p>For MiNP (a metabolite of di-isononyl phthalate), in linear regression models adjusted for age and BMI, we found that with increasing quartiles of follicular MiNP, there was a significant trend in the decrease in mean AFC (<em>P-</em>trend = 0.023) and a suggestive trend in the decrease in mean serum AMH levels (<em>P-</em>trend = 0.077). For MiDP (a metabolite of di-isodecyl phthalate), in the unadjusted regression model, we found that with increasing quartiles of follicular MiDP, there was a significant trend in the decrease in mean serum AMH levels (<em>P-</em>trend = 0.045). For MBP (a metabolite of dibutyl phthalate), in linear regression models adjusted for age and BMI, we found that with increasing quartiles of follicular MBP, there were significant trends in the decrease in the mean number of total oocytes retrieved (<em>P-</em>trend = 0.003), a decrease in the mean number of MII stage oocytes retrieved, (<em>P-</em>trend = 0.003) and a decrease in the mean peak E<sub>2</sub> levels (<em>P-</em>trend = 0.016). Although we found that with increasing quartiles of follicular mono(2-ethyl-5-oxohexyl) phthalate there was a decrease in the mean number of total and MII stage oocytes retrieved and higher follicular MEP levels were negatively associated with the mean AFC and serum AMH levels, neither trend was statistically significant. We also found that although follicular MEP levels did not show an adverse impact on ovarian function, follicular mono(2-ethyl-5-hydroxyhexyl) phthalate levels did not show an adverse impact on both the ovarian reserve and function.</p></div><div><h3>Conclusion</h3><p>In this study of 245 Indian women, higher accumulated FF levels of MiNP and MiDP were negatively associated with AFC and serum AMH levels, suggesting an adverse effect on the ovarian reserve. Higher accumulated FF levels of MBP were negatively associated with the total number of oocytes, MII stage oocytes, and peak E<sub>2</sub> values, suggesting a negative impact on ovarian function. 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To assess whether the accumulation of higher levels of selected phthalate metabolites in the follicular fluid (FF) of Indian women undergoing </span>intracytoplasmic sperm injection (ICSI) was associated with a decline in their </span></span></span>antral follicle<span> count (AFC) and/or serum antimüllerian hormone (AMH) levels, suggesting a negative impact on the ovarian reserve. To evaluate the effects of follicular phthalate metabolites on peak serum estradiol (E</span></span><sub>2</sub>) levels and the total number of oocytes and mature metaphase II (MII) stage oocytes retrieved to assess the impact of phthalate toxicity on ovarian function.</p></div><div><h3>Design</h3><p><span>A subanalysis of an ongoing prospective cohort study was conducted to examine the association between the levels of six phthalate metabolites, namely, mono-n-butyl phthalate (MBP), mono-ethyl phthalate (MEP), mono-isononyl phthalate (MiNP), mono-isodecyl phthalate (MiDP), mono(2-ethyl-5-oxohexyl) phthalate, and mono(2-ethyl-5-hydroxyhexyl) phthalate, in the FF of Indian women undergoing ICSI and their ovarian reserve markers (AFC and serum AMH levels). 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Using linear regression<span> models that were unadjusted and adjusted for maternal age and body mass index (BMI), we evaluated the association between the follicular metabolites in these women and their AFC, serum AMH levels, peak E</span></span><sub>2</sub> levels, total number of oocytes, and MII stage oocytes.</p></div><div><h3>Main Outcome Measure(s)</h3><p>To evaluate the impact of phthalate-induced ovarian toxicity on the ovarian reserve and ovarian function in Indian women undergoing ICSI by studying their accumulated levels in their FF.</p></div><div><h3>Result(s)</h3><p>For MiNP (a metabolite of di-isononyl phthalate), in linear regression models adjusted for age and BMI, we found that with increasing quartiles of follicular MiNP, there was a significant trend in the decrease in mean AFC (<em>P-</em>trend = 0.023) and a suggestive trend in the decrease in mean serum AMH levels (<em>P-</em>trend = 0.077). 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引用次数: 0

摘要

目的:研究邻苯二甲酸盐诱发的卵巢毒性对卵巢储备和卵巢功能的不良影响:研究邻苯二甲酸盐诱导的卵巢毒性对卵巢储备和卵巢功能的不利影响。评估接受卵胞浆内单精子显微注射(ICSI)的印度妇女的卵泡液(FF)中某些邻苯二甲酸酯代谢物水平的升高是否与前卵泡计数(AFC)和/或血清抗苗勒氏管激素(AMH)水平的下降有关,从而对卵巢储备功能产生负面影响。目的:评估卵泡中邻苯二甲酸酯代谢物对血清雌二醇(E2)峰值水平、取回的卵母细胞总数和成熟分裂期II(MII)期卵母细胞数的影响,以评估邻苯二甲酸酯毒性对卵巢功能的影响:研究发现,接受卵巢综合征卵巢囊肿综合征(ICSI)治疗的印度妇女的卵巢囊肿及其卵巢储备标志物(AFC 和血清 AMH 水平)与这些卵泡酸单正丁酯(MBP)、邻苯二甲酸单乙酯(MEP)、邻苯二甲酸单异壬酯(MiNP)、邻苯二甲酸单异癸酯(MiDP)、邻苯二甲酸单(2-乙基-5-氧代己基)酯和邻苯二甲酸单(2-乙基-5-羟基己基)酯有关联。研究这些卵泡邻苯二甲酸酯代谢物水平与E2峰值水平、取回的卵母细胞总数和MII期卵母细胞数的关系:印度一家转诊医院的体外受精中心:共纳入了 245 名在 2017 年 4 月至 2020 年 3 月中旬期间同意接受卵母细胞取样的印度女性。每名妇女为研究提供一份 FF 样本。该样本接受了六种邻苯二甲酸酯代谢物的筛查。这些样本是在2019年冠状病毒疾病大流行之前采集的:采用液相色谱-串联质谱法,对 245 名妇女的 FF 中六种邻苯二甲酸酯代谢物的总含量进行了量化。通过线性回归模型,我们评估了这些女性的卵泡代谢物与其AFC、血清AMH水平、E2峰值水平、卵母细胞总数和MII期卵母细胞之间的关系:主要结果测量指标:通过研究FF中的累积水平,评估邻苯二甲酸盐诱导的卵巢毒性对接受ICSI的印度妇女的卵巢储备和卵巢功能的影响:就 MiNP(邻苯二甲酸二异壬酯的代谢产物)而言,在根据年龄和体重指数调整后的线性回归模型中,我们发现随着卵泡 MiNP 四分位数的增加,平均 AFC 呈显著下降趋势(P-trend = 0.023),平均血清 AMH 水平呈提示性下降趋势(P-trend = 0.077)。对于 MiDP(邻苯二甲酸二异癸酯的代谢产物),在未调整的回归模型中,我们发现随着卵泡 MiDP 四分位数的增加,平均血清 AMH 水平呈显著下降趋势(P-trend = 0.045)。对于 MBP(邻苯二甲酸二丁酯的代谢产物),在根据年龄和体重指数调整后的线性回归模型中,我们发现随着卵泡 MBP 四分位数的增加,取卵总卵母细胞的平均数量呈显著下降趋势(P-trend = 0.003),取卵 MII 阶段卵母细胞的平均数量呈显著下降趋势(P-trend = 0.003),E2 峰值的平均水平呈显著下降趋势(P-trend = 0.016)。尽管我们发现,随着卵泡单(2-乙基-5-氧代己基)邻苯二甲酸酯四分位数的增加,总卵母细胞和 MII 期卵母细胞的平均取卵数减少,卵泡 MEP 水平越高与平均 AFC 和血清 AMH 水平呈负相关,但这两种趋势均无统计学意义。我们还发现,虽然卵泡 MEP 水平未显示出对卵巢功能的不利影响,但卵泡单(2-乙基-5-羟基己基)邻苯二甲酸酯水平也未显示出对卵巢储备和功能的不利影响:在这项对 245 名印度妇女进行的研究中,MiNP 和 MiDP 的累积 FF 水平较高与 AFC 和血清 AMH 水平呈负相关,表明对卵巢储备功能有不利影响。MBP的累积FF水平较高与卵母细胞总数、MII期卵母细胞和E2峰值呈负相关,表明对卵巢功能有负面影响。尽管我们发现邻苯二甲酸盐诱导的卵巢毒性对选定的邻苯二甲酸盐代谢物具有统计学意义,但不能排除多种邻苯二甲酸盐在卵巢微环境中的累积效应的作用,这需要进一步研究。
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The impact of follicular fluid phthalate metabolites on the ovarian reserve and ovarian function in Indian women undergoing intracytoplasmic sperm injection

Objective

To investigate the adverse effects of phthalate-induced ovarian toxicity on the ovarian reserve and ovarian function. To assess whether the accumulation of higher levels of selected phthalate metabolites in the follicular fluid (FF) of Indian women undergoing intracytoplasmic sperm injection (ICSI) was associated with a decline in their antral follicle count (AFC) and/or serum antimüllerian hormone (AMH) levels, suggesting a negative impact on the ovarian reserve. To evaluate the effects of follicular phthalate metabolites on peak serum estradiol (E2) levels and the total number of oocytes and mature metaphase II (MII) stage oocytes retrieved to assess the impact of phthalate toxicity on ovarian function.

Design

A subanalysis of an ongoing prospective cohort study was conducted to examine the association between the levels of six phthalate metabolites, namely, mono-n-butyl phthalate (MBP), mono-ethyl phthalate (MEP), mono-isononyl phthalate (MiNP), mono-isodecyl phthalate (MiDP), mono(2-ethyl-5-oxohexyl) phthalate, and mono(2-ethyl-5-hydroxyhexyl) phthalate, in the FF of Indian women undergoing ICSI and their ovarian reserve markers (AFC and serum AMH levels). To investigate the association of these follicular phthalate metabolite levels with the peak E2 levels and the total number of oocytes and number of MII stage oocytes retrieved.

Setting

In vitro fertilization center in a referral hospital in India.

Patient(s)

A total of 245 consenting Indian women who had undergone oocyte retrieval between April 2017 and mid-March 2020 were included. Each woman contributed one FF sample to the study. This was screened for six phthalate metabolites. The samples were collected before the coronavirus disease 2019 pandemic.

Intervention(s)

Using liquid chromatography-tandem mass spectrometry, the total levels of six phthalate metabolites were quantified in the FF of 245 women. Using linear regression models that were unadjusted and adjusted for maternal age and body mass index (BMI), we evaluated the association between the follicular metabolites in these women and their AFC, serum AMH levels, peak E2 levels, total number of oocytes, and MII stage oocytes.

Main Outcome Measure(s)

To evaluate the impact of phthalate-induced ovarian toxicity on the ovarian reserve and ovarian function in Indian women undergoing ICSI by studying their accumulated levels in their FF.

Result(s)

For MiNP (a metabolite of di-isononyl phthalate), in linear regression models adjusted for age and BMI, we found that with increasing quartiles of follicular MiNP, there was a significant trend in the decrease in mean AFC (P-trend = 0.023) and a suggestive trend in the decrease in mean serum AMH levels (P-trend = 0.077). For MiDP (a metabolite of di-isodecyl phthalate), in the unadjusted regression model, we found that with increasing quartiles of follicular MiDP, there was a significant trend in the decrease in mean serum AMH levels (P-trend = 0.045). For MBP (a metabolite of dibutyl phthalate), in linear regression models adjusted for age and BMI, we found that with increasing quartiles of follicular MBP, there were significant trends in the decrease in the mean number of total oocytes retrieved (P-trend = 0.003), a decrease in the mean number of MII stage oocytes retrieved, (P-trend = 0.003) and a decrease in the mean peak E2 levels (P-trend = 0.016). Although we found that with increasing quartiles of follicular mono(2-ethyl-5-oxohexyl) phthalate there was a decrease in the mean number of total and MII stage oocytes retrieved and higher follicular MEP levels were negatively associated with the mean AFC and serum AMH levels, neither trend was statistically significant. We also found that although follicular MEP levels did not show an adverse impact on ovarian function, follicular mono(2-ethyl-5-hydroxyhexyl) phthalate levels did not show an adverse impact on both the ovarian reserve and function.

Conclusion

In this study of 245 Indian women, higher accumulated FF levels of MiNP and MiDP were negatively associated with AFC and serum AMH levels, suggesting an adverse effect on the ovarian reserve. Higher accumulated FF levels of MBP were negatively associated with the total number of oocytes, MII stage oocytes, and peak E2 values, suggesting a negative impact on ovarian function. Although we found that phthalate-induced ovarian toxicity was statistically significant for selected phthalate metabolites, the role of the cumulative effect of multiple phthalates in the ovarian microenvironment cannot be ruled out and needs to be investigated further.

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来源期刊
F&S science
F&S science Endocrinology, Diabetes and Metabolism, Obstetrics, Gynecology and Women's Health, Urology
CiteScore
2.00
自引率
0.00%
发文量
0
审稿时长
51 days
期刊最新文献
Mitochondrial activator BGP-15 protects sperm quality against oxidative damage and improves embryo developmental competence. Receptive window might be shorter in patients with endometriosis and lesions cyclically prepare for implantation. Sphingosine 1-phosphate acts as proliferative and fibrotic cue in leiomyoma cells. Blood-based inflammatory markers in female infertility: evidence from Mendelian randomization analysis. Phthalates are detected in the follicular fluid of adolescents and oocyte donors with associated changes in the cumulus cell transcriptome.
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