Fertility Disorders

Researchers have consistently shown that prenatal exposure to Di (2-ethyhexyl) phthalate harms the reproductive system in male mice and causes fertility defects. In a new study, scientists have shown that the combination of DEHP and a high-fat diet in pregnant mice can cause more damage to pups than each factor alone. Researchers have consistently shown that prenatal exposure to Di (2-ethyhexyl) phthalate harms the reproductive system in male mice and causes fertility defects. In a new study, scientists from the University of Illinois Urbana-Champaign have shown that the combination of DEHP and a high-fat diet in pregnant mice can cause more damage to pups than each factor alone. Male reproductive disorders are a growing issue due to the global decrease in sperm count and quality. Concerningly, chemicals like DEHP, which can be found in food storage containers, pharmaceuticals, and building materials, have been found to be one of the contributing factors. The toxicity of DEHP is due to its ability to mimic the hormones in our bodies, leading to long-term effects on health. "The scientific community is aware of the fact that the current generation of men produce half as much sperm compared to the previous one," said CheMyong Jay Ko (EIRH), a professor of veterinary medicine. "Although it is shocking, not much attention is paid to understanding the causes." The researchers used the Barker hypothesis as a guiding principle for their study. Proposed by the British physician and epidemiologist David Barker, the hypothesis argued that the nine months in utero are one of the most critical periods in a person's life and can shape their future health trajectories. "The Barker hypothesis primarily focuses on nutrition and we wanted to test whether the mother's diet could change the health of the next generation," Ko said. "Additionally, unlike the previous generation, we are constantly exposed to chemicals like DEHP, which can alter how our bodies function. We wanted to ask whether the exposure to both these factors can cause growing babies to have lesser functioning reproductive systems." In the past, both the Ko lab and other research groups have shown that prenatal exposure to DEHP decreases testosterone levels and causes fertility defects in male mice. Additionally, scientists have shown that maternal high-fat diet can also decrease sperm counts in male offspring. However, the effects of both together had not been studied. The researchers used four groups of pregnant mice; one was a control and the other three were either exposed to DEHP, or a high-fat diet, or a combination of the two. They then followed each litter, which contained an average of 6 male and 6 female pups. "Surprisingly, we found that a high-fat diet had a more damaging effect on the male reproductive systems compared to DEHP alone and the pups born from mothers who had been treated with both had the worst outcomes," Ko said. The researchers measured the weight of the body and different reproductive organs in pups during different stages of growth and puberty. They found that although the body weight of pups born from moms on a high-fat diet alone or in combination with DEHP was higher than the other pups, the weight of the reproductive organs was lower. They also found that these mice produced less sperm and had lower testosterone levels. By staining the tissues, the researchers found that the reproductive organs had abnormal cells, which were contributing to the gonadal dysfunction. "In our studies, we used these mice as a model. Although we need to confirm these results in humans, this study should serve as a warning to our generation that we need to be careful about our environment and diet during pregnancy," Ko said.

In some EU countries, 17-OHPC medicines have been authorised as injections for preventing pregnancy loss or premature birth. Credit: Victoria Moloman / Shutterstock.com. The European Medicines Agency’s (EMA) Pharmacovigilance Risk Assessment Committee (PRAC) has advised the suspension of marketing authorisations for therapeutics containing 17-hydroxyprogesterone caproate (17-OHPC) in the European Union (EU). The recommendation follows a review that raised concerns about an as-yet unconfirmed risk of cancer in individuals exposed to 17-OHPC in the womb. The PRAC review included a large population-based study spanning 50 years. Despite the low number of cancer cases and limitations such as insufficient information on cancer risk factors, the committee concluded that a possible cancer risk could not be ruled out. In addition to cancer risk concerns, new studies have indicated that 17-OHPC is ineffective in preventing premature birth. See Also: NICE recommends Rhythm’s Imcivree for rare genetic obesity disorder Glenmark to market BeiGene’s oncology medicines in India PRAC examined a study involving more than 1,700 pregnant women with a history of preterm delivery which found that 17-OHPC did not outperform a placebo in preventing recurrent preterm births or related medical complications in newborns. Two published meta-analyses further confirmed the lack of efficacy in preventing preterm birth. For other authorised uses of 17-OHPC, such as the treatment of gynaecological and fertility disorders, PRAC found limited evidence of effectiveness. The committee’s review process also included consultations with experts in obstetrics, gynaecology, fertility treatment, and patient representatives. In some EU countries, 17-OHPC medicines have been authorised as injections for preventing pregnancy loss or premature birth in pregnant women. They are also used for treating conditions related to progesterone deficiency. In a media statement, EMA said: “In view of the concern raised by the possible risk of cancer in people exposed to 17-OHPC in the womb, together with the data on the effectiveness of 17-OHPC in its authorised uses, PRAC considered that the benefits of 17-OHPC do not outweigh its risks in any authorised use. “The committee is therefore recommending the suspension of the marketing authorisations for these medicines. Alternative treatment options are available.”

The European Medicines Agency (EMA) on Friday recommended withdrawing approval for a drug used to prolong gestation, citing a "possible but unconfirmed" risk of cancer and new studies questioning its effectiveness in preventing premature births.The advice is reminiscent of last year's FDA decision to withdraw approval for Covis Pharma's Makena (hydroxyprogesterone caproate) — the sole preterm birth drug that had been approved in the US — after a follow-up study found that it was ineffective.The EMA said its Pharmacovigilance Risk Assessment Committee (PRAC), which monitors drug-related side effects, conducted a review of 17-hydroxyprogesterone caproate (17-OHPC), a synthetic hormone therapy administered as an injection to pregnant women at risk of preterm delivery.PRAC examined findings from a large population-based study that looked at the risk of cancer in people who had been exposed to 17-OHPC in the womb, over a period of about 50 years from the time they were born. While data indicated a potential cancer risk in these individuals compared to those unexposed to the medication, PRAC acknowledged that there was a low number of cancer cases in the study, which had other limitations, such as limited information on cancer risk factors.The committee concluded that the risk of cancer in people exposed to 17-OHPC in utero "is possible, but cannot be confirmed due to uncertainties."PRAC's review also considered new studies that showed 17-OHPC was not effective in preventing premature birth, the primary indication for which the drug was approved in some EU countries. The group considered a study involving over 1700 pregnant women with a history of preterm delivery, showing that 17-OHPC was no better than placebo at preventing recurrent premature births or related complications in newborns. It also reviewed two published meta-analyses that drew similar conclusions. The group said there are "limited data" on the drug's benefit in other authorised uses as well.Based on these findings, PRAC determined that the potential benefits of 17-OHPC "do not outweigh its risks in any authorised use," which also includes the treatment of various gynaecological and fertility disorders, including those related to progesterone deficiency.