Significant changes in follicular fluid phthalate metabolite levels reflect the lifestyle changes brought about by the strict COVID-19 lockdown in India

Ovarian Biology
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VOLUME 3, ISSUE 3, P237-245, AUGUST 01, 2022

Authors:

Firuza Rajesh Parikh, M.D., Ph.D., Shonali Uttamchandani, B.Sc., Nandkishor Naik, B.Sc., Madhavi Panpalia, M.S., Mangesh Sanap, M.Sc., Dhananjaya Kulkarni, Ph.D., Prachi Sinkar, M.D., Pratiksha Khandare, M.Sc., Prashant Makwana, M.Sc., Smita Gawas, B.Sc., Anahita Pandole, M.D., D.N.B., Rajesh Parikh, M.D., Dip.N.B.E.

Abstract:

Objective

To assess if the unprecedented changes in lifestyle because of the lockdown initiated by the COVID-19 pandemic, which altered human behavior, and influenced purchase and consumption patterns, may have had an impact on the exposure to phthalates in Indian women undergoing in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI). To evaluate if the effects of the strict and lengthy lockdown in India, which promoted the new norms of stay-at-home and work-from-home, closure of beauty parlors, and restriction on public gatherings, may have contributed to a decrease in the exposure to phthalates like dibutyl phthalate and diethyl phthalate. These chemicals are found in many personal care products (PCPs) which include cosmetics and fragrances. To investigate if the extensive use of flexible single-use plastic in personal protective equipment like face masks/gloves and in plastic packaging used for online purchases, food takeaways, and home deliveries of essentials and groceries during the COVID-19 pandemic, in an attempt to provide a contact-free delivery system may have inadvertently led to an increase in exposure to phthalates like di(2-ethylhexyl) phthalate, di-isononyl phthalate, and di-isodecyl phthalate which are plasticizers used in manufacturing flexible plastic.


Design

A comparative study of the levels of six phthalate metabolites detected in follicular fluid (FF) of Indian women undergoing IVF/ICSI 1 year before and immediately after the lockdown initiated by the COVID-19 pandemic.


Setting

In vitro fertilization center in a large referral hospital in India.


Patient(s)

A total of 176 Indian women seeking treatment for infertility and undergoing oocyte retrieval were included after obtaining consent. Each woman contributed one FF sample to the study. Group A (n = 96) women (mean age, 34.0 [±3.9] years, and mean BMI, 25.4 [±4.8]) had their FF samples collected and screened between January 2019 and mid-March 2020, 1 year before the lockdown. Group B (n = 80) women (mean age, 33.9 [±4.1] years, and mean BMI, 25.0 [±4.4]) had their FF collected and screened post the lockdown between October 2020 and June 2021. Both groups were matched by age and BMI.


Intervention(s)

The cryopreserved FF samples of 176 women were processed using enzymatic deconjugation as well as the solid-phase extraction technique, and analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) to detect the total levels of six phthalate metabolites.


Main Outcome Measure(s)

To evaluate the impact of the COVID-19 lockdown on the change in the phthalate metabolite levels in the FF of Indian women undergoing IVF/ICSI pre and post the lockdown.


Result(s)

The median levels of mono-n-butyl phthalate (1.64 ng/ml in group A vs. 0.93 ng/ml in group B; P<.001) and mono-ethyl phthalate (5.25 ng/ml in group A vs. 3.24 ng/ml in group B; P<.001) metabolites of dibutyl phthalate and diethyl phthalate found in PCPs including cosmetics and fragrances were significantly higher in the FF of 96 women (group A) compared with the levels seen in the FF of 80 women (group B). However, the median levels of mono-isononyl phthalate (0.11ng/ml in group A vs. 0.13 ng/ml in group B; P<.001), mono-isodecyl phthalate (0.11 ng/ml in group A vs. 0.14 ng/ml in group B; P<.001), and mono(2-ethyl-5-oxohexyl) phthalate (0.13 ng/ml in group A vs. 0.14 ng/ml in group B; P=.023) metabolites of di-isononyl phthalate, di-isodecyl phthalate, and di(2-ethylhexyl) phthalate used as plasticizers were significantly higher in the FF of women in group B compared with women in group A.


Conclusion(s)

The significant drop in mono-n-butyl phthalate and mono-ethyl phthalate levels, accumulated in the FF of 80 Indian women in group B reflects a decrease or absence of usage patterns of PCPs, including cosmetics and fragrances, thereby suggesting that these women may have deprioritized their use during the COVID-19 pandemic giving preference to personal hygiene and safety. Whereas the unprecedented increase in the use of flexible single-use plastic that became our first line of defense against the coronavirus during the COVID-19 pandemic might be responsible for the accumulation of significantly higher levels of mono-isononyl phthalate, mono-isodecyl phthalate, and mono(2-ethyl-5-oxohexyl) phthalate in FF of the same group.

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Go to the profile of Pandiyan  Natarajan
4 months ago

Did the phthalate metabolites affect fertilization, cleavage, implantation or live birth rates?

Congratulations to the Dr Firuza Rajesh Parikh and her co workers for that interesting paper clearly demonstrating the pervasive nature of the phthalates reaching the follicular fluid. It would be interesting to know if this affected the fertilization, cleavage, implantation or live birth rates. 

Plastics are ubiquitous and affect every walk of our life. Do they also affect the gametes, Embryo  and Reproduction?  If they do, why are we using plastics in our Andrology and Embryology laboratory. If they don’t affect the gametes or the embryo, how does the presence of phthalates in follicular fluid matter? 

Professor Dr Pandiyan Natarajan.

Chief Consultant in Andrology and Reproductive Sciences,

Apollo 24/7, NOVA IVF FERTILITY,

Chettinad Super Speciality Hospital (Retired)

Professor Emeritus, The Tamil Nadu Dr MGR Medical University.

Go to the profile of Firuza
3 months ago

Thank you for your interest in our study. 

Did the phthalate metabolites affect fertilization, cleavage, implantation or live birth rates?

While this particular study demonstrated how the unprecedented change in lifestyle because of the COVID-19 initiated lockdown had an impact on exposure to phthalates in Indian women undergoing IVF, we believe that the true impact of phthalates on embryological parameters and reproductive outcome would be best assessed in a larger study preferably only on women who were screened before the COVID-19 pandemic (normal life scenario) where the drastic change in lifestyle had not temporarily influenced exposure to phthalates.

Because in this study, the 80 women in Group B (screened after the lockdown) did not show a decline in the levels of all the 6 phthalate metabolites in their follicular fluid (FF) but instead showed a simultaneous significant decline in the levels of MBP and MEP along with a significant increase in the levels of MiNP, MiDP and MEOHP owing to the unprecedented but temporary change in lifestyle, it was likely that the impact on embryological parameters and reproductive outcome between the two groups would not be significantly different. Besides, we felt that investigating this in the current study might actually be misleading.

We are currently looking at our larger pre pandemic study to understand the effects of phthalates detected in the FF on embryological parameters and reproductive outcome.

Plastics are ubiquitous and affect every walk of our life. Do they also affect the gametes, Embryo and Reproduction?  If they do, why are we using plastics in our Andrology and Embryology laboratory. If they don’t affect the gametes or the embryo, how does the presence of phthalates in follicular fluid matter? 

Your concern is absolutely justified. Phthalates are now being labeled as the 21st century’s plague for reproductive health which emphasizes the concern.

Phthalates are found in flexible plastic so medical tubing, blood bags, catheters are more likely to have phthalates. Because petri dishes/ tubes used in laboratories are made of a more hard plastic they are less likely to have phthalates although the chances of containing Bisphenol A (BPA) another endocrine disrupting chemical is high. Therefore there are more studies that have screened disposables used in an embryology and andrology laboratory for BPA and often studies have reported an absence of BPA. However, since it is not possible to completely rule out the presence of phthalates or BPA in plastics used in laboratories, in an ideal situation we would be better off going back to using glassware. For this study, glass vacutainers were used to store the FF samples thereby reducing the possibility of contamination with parent phthalates at the time of collection and storage.

 Firuza R. Parikh, M.D., Ph.D.,

Jaslok-FertilTree International Fertility Centre,

Department of Assisted Reproduction & Genetics,

15,  Dr. G. Deshmukh Marg,

Mumbai 400026