Category: Obstetrics & Gynaecology

Effects of Fathers’ Prenatal Alcohol Exposure Manifests in Offspring

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Researchers have discovered that males exposed to alcohol in utero later pass on those effects to their offspring during foetal development, through reduced placental efficiency. The study appears in FASEB Journal.

Dr Michael Golding, an associate professor at Texas A&M University has spent years investigating the father’s role, with regard to drugs and alcohol, in foetal development. Studies have shown that males pass down more than just their genetics, Dr Golding said, but exactly how that process works and the its consequences are still largely unknown.

“When you look at the data from throughout human history, there’s clear evidence that there’s something beyond just genetics being inherited from the male,” Dr Golding said. “So, if that data is solid, we’ve got to start looking more at male behaviour.

“Say you had a parent who was exposed to starvation – they could pass on what you might call a ‘thriftiness,’ where their kids can derive more nutrition from less food,” he said. “That could be a positive if they grow up in a similar environment, or they could grow up in a time when starvation isn’t an issue and they might be more prone to obesity or metabolic syndromes. That kind of data is clearly present in clinical data from humans.”

Epigenetics, which is Dr Golding’s area of study of how things beyond genes, such as behaviour and environment, affect development is called. One of the big questions in the search for answers on how male prenatal behaviour can impact foetal growth has been the way these epigenetic factors manifest.

The team has shown that prenatal exposure to alcohol in males can manifest in the placenta: in mice, offspring of fathers exposed to alcohol have a number of placenta-related difficulties, including increased foetal growth restriction, enlarged placentas, and decreased placental efficiency.

“The placenta supplies nutrients to the growing foetus, so foetal growth restriction can be attributed to a less efficient placenta. This is why placental efficiency is such an important metric; it tells us how many grams of foetus are produced per gram of placenta,” said Thomas, a graduate student at Texas A&M. “With paternal alcohol exposure, placentas become overgrown as they try to compensate for their inefficiency in delivering nutrients to the foetus.”

However,while these increases happened frequently in male offspring, the frequency varied greatly based on the mother; however, the same increases were far less frequent in female offspring. Dr Golding thinks that although information is passed from the father, the mother’s genetics and the offspring’s sex are also involved.

“This is a novel observation because it says that there’s some complexity here,” Dr Golding said. “Yes, men can pass things on to their offspring beyond just genetics, but the mom’s genetics can interpret those epigenetic factors differently, and that ultimately changes the way that the placenta behaves.”

These results don’t draw a clear line in how drinking in human males prior to conception impacts foetal development, but they continue to at least point to it being a question that needs to be explored. 

Dr Golding is hoping that more questions will be asked about male prenatal behaviour so that there’s more data from which to work.

“The thing that I want to ultimately change is this stigma surrounding the development of birth defects,” Dr Golding said. “There’s information coming through in sperm that is going to impact the offspring but is not tied to the genetic code; it’s in your epigenetic code, and this is highly susceptible to environmental exposures, so the birth defects that we see might not be the mother’s fault; they might be the father’s or both, equally.”

Source: Texas A&M University

Study Confirms COVID Vaccination does not Affect Fertility in IVF

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Vaccination against COVID did not affect fertility outcomes in patients undergoing in-vitro fertilisation (IVF), according to a new study. The findings, which were published in Obstetrics & Gynecology, add to the growing body of evidence providing reassurance that COVID vaccination does not affect fertility.

Investigators compared rates of fertilisation, pregnancy, and early miscarriage in IVF patients who had received two doses of vaccines manufactured by Pfizer or Moderna with the same outcomes in unvaccinated patients.

“The study found no significant differences in response to ovarian stimulation, egg quality, embryo development, or pregnancy outcomes between the vaccinated compared to unvaccinated patients.” said first author Devora Aharon, MD.

The study involved patients whose eggs were frozen and then thawed for in vitro fertilisation and womb transfer, and patients who underwent medical treatment to stimulate the development of eggs. The two groups of patients who underwent frozen-thawed embryo transfer (214 vaccinated and 733 unvaccinated) had similar rates of pregnancy and early pregnancy loss. The two groups of patients who underwent ovarian stimulation (222 vaccinated and 983 unvaccinated) had similar rates of eggs retrieved, fertilisation, and embryos with normal numbers of chromosomes, among several other measures.

The authors of the study anticipate that the findings will ease the anxiety of people considering pregnancy. 

Patients undergoing IVF treatment are closely tracked, enabling the researchers to capture early data on the implantation of embryos in addition to pregnancy losses that might be undercounted in other studies.

Previous studies have found that COVID vaccination helped protect pregnant persons (already at greater risk from severe illness and death from COVID) from severe illness, conferred antibodies to their infants, and did not raise the risk of preterm birth or foetal growth problems.

Source: EurekAlert!

Assisted Reproductive Technology Doubled Birth Rates in Middle-aged Women

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A study found birth rates among middle-aged women in Northern European increased thanks to assisted reproductive technologies.

The study examined the total population of women aged 40–49 years between 2008–2018 in Denmark, Norway, and Sweden, birth rates increased in Denmark and Sweden, and births resulting from assisted reproductive technology doubled in all three countries. The findings were published in Acta Obstetricia et Gynecologica Scandinavica.

The study found that use of hormonal contraception increased among women aged 40–44 years in Denmark from 24% to 31%, in Sweden from 27% to 30%, and in Norway from 22% to 24%. Additionally, birth rates among women 40–44 years increased from 9.5 to 12 per 1000 women in Denmark and from 11.7 to 14.3 per 1,00 in Sweden, while they remained stable in Norway at approximately 11 per 1000 women.

In women aged 40–49 years, there was a doubling of assisted conceptions in Denmark from 0.71 to 1.71 per 1000 women; in Sweden from 0.43 to 0.81 per 1000; and in Norway from 0.25 to 0.53 per 1000. The study also found that Sweden had the highest induced abortion rate (7.7 to 8.1 per 1000 women) in women aged 40–49 years during the study period.

“This study confirms the trend of postponing childbirth observed for most of Europe and demonstrates the important role of assisted reproductive technology on birth rates in this age group,” said lead author Ingela Lindh, MD, of Sahlgrenska University Hospital. “The study provides valuable information to improve women’s knowledge about their fertility.”

Source: Wiley

Synthetic Progestogen in Utero Leads to Doubled Cancer Rate in Offspring

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In utero exposure to a synthetic progestogen used to prevent miscarriage can lead to an increased risk of developing cancer, according to a new study.

The study by researchers at The University of Texas Health Science Center at Houston (UTHealth Houston) was published in the American Journal of Obstetrics and Gynecology.

The drug, 17α-hydroxyprogesterone caproate (17-OHPC), is a synthetic progestogen frequently used by women in the 1950s and 1960s, and is still prescribed today to women to help prevent preterm birth. Progesterone helps the uterus grow during pregnancy and prevents early contractions that may lead to miscarriage.

“Children who were born to women who received the drug during pregnancy have double the rate of cancer across their lifetime compared to children born to women who did not take this drug,” said the study’s lead author, Caitlin C. Murphy, PhD, MPH, associate professor in the Department of Health Promotion and Behavioral Sciences at UTHealth School of Public Health in Houston. “We have seen cancers like colorectal cancer, pancreatic cancer, thyroid cancer, and many others increasing in people born in and after the 1960s, and no one really knows why.”

Researchers reviewed data from the Kaiser Foundation Health Plan on women who received prenatal care between June 1959 and June 1967, and the California Cancer Registry, which traced cancer in offspring through 2019.

Out of more than 18 751 live births, researchers discovered 1008 cancer diagnoses were made in offspring ages 0 to 58 years. Additionally, a total of 234 offspring were exposed to 17-OHPC during pregnancy. Offspring exposed in utero had cancer detected in adulthood at more than twice the rate of of those unexposed: 65% of cancers occurred in adults younger than 50.

“Our findings suggest taking this drug during pregnancy can disrupt early development, which may increase risk of cancer decades later,” Murphy said “With this drug, we are seeing the effects of a synthetic hormone. Things that happened to us in the womb, or exposures in utero, are important risk factors for developing cancer many decades after we’re born.”

A new randomised trial shows there is no benefit of taking 17-OHPC, and that it does not reduce the risk of preterm birth, according to Murphy.

The U.S. Food and Drug Administration proposed in October 2020 that this particular drug be withdrawn from the market.

Source: University of Texas Health Science Center at Houston

Thyroid Conditions may Affect Egg Reserves in Ovaries

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In an analysis published in Reproductive Medicine and Biology, researchers found evidence that thyroid conditions in women could negatively impact egg reserves in their ovaries.

Hypothyroidism is a disease that is prevalent in women, even in those of reproductive age. Thyroid hormones are involved in the control of the menstrual cycle. Oocytes express cell surface receptors for thyroid hormones that affect the actions of follicle-stimulating hormone and luteinising hormone through steroid biosynthesis. As such, thyroid dysfunction disturbs menstrual regularity and ovulation. However, the effects of low thyroid hormone levels (hypothyroidism) and thyroid autoimmune diseases on the functioning of a woman’s ovaries are not fully understood. This analysis aimed to investigate whether hypothyroidism and/or thyroid autoimmunity  affect the ovarian reserve, evaluated using levels of anti-Mullerian hormone (AMH).

The researchers found nine relevant trials, and their findings indicated that hypothyroidism and thyroid autoimmunity can negatively impact a woman’s ovarian reserve, or the total number of healthy immature eggs in the ovaries.

“Our age-stratified analysis demonstrated that thyroid autoimmunity and hypothyroidism possibly have different impacts on the ovarian reserve. It provides an important clue in determining how these conditions affect the development of ovarian follicles,” said senior author Akira Iwase, MD, PhD, of the Gunma University Graduate School of Medicine, in Japan.

Source: Wiley

After a Pregnancy, Natural Killer Cells Suppress Tumours

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After a pregnancy, breast cells call in Natural Killer T (NKT) cells as reinforcements to prevent tumours from arising, according to a study published in Cell Reports. This finding from the lab of Associate Professor Camila dos Santos at Cold Spring Harbor Laboratory (CSHL) illuminates a new way in which pregnancy reduces the risk of breast cancer.

Two lines of defence exist in the immune system: the innate response, which involves immune cells that attack any foreign molecule they encounter, and the adaptive response, which consists of immune cells that respond specifically to calls for help. NKT cells are a unique subset of cells that are present throughout the body which can participate in both responses. 

CSHL graduate student Amritha Varshini Hanasoge Somasundara said that after a pregnancy: “There is an increase in this specific [NKT] cell type, and only in the mammary gland. We don’t see the expansion everywhere else in the body, even though NKT cells are present everywhere else in the body.”

The team sought to uncover the reason behind the larger number of NKT cells were doing in the breast tissue. Hanasoge discovered that in mice, breast epithelial cells, which line lactation ducts, produce a specific protein called CD1d after pregnancy. If the cells did not present CD1d, no increase in NKT cells was seen in the tissue; the epithelial cells became cancerous and grew into tumours. Hanasoge and dos Santos think that CD1d molecules are calling in NKT cells to monitor the epithelial cells in the breast tissue after pregnancy. If they become cancerous, the NKT cells can quickly kill them to prevent tumour growth.

The team’s findings establish a novel link between pregnancy and the immune system in preventing breast cancer. They want to know how these findings can be translated into humans and what other factors may influence an abundance of NKT cells in breast tissue, such as aging and menopause, which are both associated with increased breast cancer risk.

Discussing the results, Associate Professor dos Santos said: “One of the hypotheses that we are working on now is: do pregnancies later on in life bring in the same expansion of the same subtypes of immune cells as pregnancies that took place early in life?”

Source: Cold Spring Harbor Laboratory

Smoking During Pregnancy Can Impact a Subsequent Pregnancy

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University of Southampton researchers have found that the link between smoking at the start of pregnancy and having a smaller baby may extend to future pregnancies.

The research team studied data between 2003 and 2018 for nearly 17 000 mothers who received antenatal care for their first two pregnancies. 

The findings, published in PLOS One, showed that, compared to non-smokers, women who smoked at the start of their first pregnancy were more likely to have a baby born smaller than expected in their second pregnancy. This held true even where they quit by the start of their second pregnancy.

The link between smoking during a pregnancy and that baby’s birth weight is well established. However, until now there has been limited evidence on the impact of maternal smoking on following pregnancies.

This study found that for women who smoked but did not smoke at the start of either pregnancy, there was no extra risk of a small for gestational age (SGA) baby in the second pregnancy compared to non-smokers. A mother who smoked ten or more cigarettes a day at the start of both of her first two pregnancies had the highest odds of SGA birth.

Study leader Dr Nisreen Alwan, Associate Professor at the University of Southampton, said: “It is important to encourage women to quit smoking before pregnancy and to not resume smoking after the baby is born. Resources that support mothers to quit and maintain smoking cessation are needed.”

First author Elizabeth Taylor said: “Women who smoke between pregnancies can reduce the risk of having a SGA baby by stopping smoking before the start of their next pregnancy. The period between pregnancies is when most mothers have close contact with health and care professionals and may require support to stop smoking.”

It is hoped that these findings and future research will encourage healthcare professionals and commissioners to provide better support to women before and between pregnancies, helping them to quit smoking, leading to better health for both mothers and children.

Source: University of Southampton

Placental Cells Could Help Growth-restricted Babies

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Healthy placenta from mothers of healthy newborns could potentially reduce brain injury in growth-restricted babies, University of Queensland researchers suggest. UQ’s Dr Julie Wixey said the study found stem cells sourced from a healthy placenta may reduce damaging inflammation in these babies after only three days.

“There is currently no treatment to protect the brains of a growth-restricted baby,” Dr Wixey said. “Up to 50% of them have long term issues ranging from mild learning and behavioural disorders all the way through to cerebral palsy. We know there’s inflammation in the brain and it doesn’t cease once these babies are born.  

“Our study has shown we could reduce inflammation and ongoing brain injury by treating these newborns on the day they’re born using a combination of two types of stem cells – endothelial colony forming cells and mesenchymal stromal cells – isolated from a healthy human placenta.”

About 32 million growth-restricted babies are born around the world each year. Many of them did not receive enough nutrients and oxygen from the placenta.

“Our research has found after just three days, the combination stem cell therapy not only reduced inflammation but also, importantly, appeared to repair damaged blood vessels in the brain in animal models,” Dr Wixey said. “We’re really excited by the outcomes of this study and we hope it’ll improve these babies’ lives long term.”

Dr Jatin Patel, who co-invented the stem cell harvesting technology, said: “This has been a fantastic collaborative study and demonstrates the exciting potential of stem cell therapy in the near future in treating unwell babies.

“We are now working towards scaling up our patented stem cell technology, that will result in greater quantities of cells to drive and expand the preclinical animal studies with the aim of progressing towards a human trial.”

The study was published in npj Regenerative Medicine. The researchers will now investigate the longer-term outcomes of the combination stem cell treatment.

Source: University of Queensland

Cannabis Use in Pregnancy Predisposes Children to Stress and Anxiety

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Women who use cannabis during pregnancy, such as for stress and anxiety relief, may inadvertently predispose their children to stress susceptibility and anxiety, according to a study published in PNAS.

As cannabis continues to be legalised worldwide, many people mistakenly believe that cannabis use is without significant health risks. In line with this softening public opinion, cannabis has emerged as one of the most consumed recreational drugs of abuse during pregnancy, however the impact of maternal cannabis use on foetal and childhood development is unclear.

“We know that cannabinoid signaling plays a role in modulating stress, which is why some people use cannabis to reduce anxiety and relax,” said first author Professor Yoko Nomura at CUNY Graduate Center and Queens College. “But our study shows that in utero exposure to cannabis has the opposite effect on children, causing them to have increased levels of anxiety, aggression, and hyperactivity compared to other children who were not exposed to cannabis during pregnancy.”

Researchers examined placental gene expression and early childhood behaviour and physiology in a long-term study of 322 mother-child pairs who were drawn from an ongoing New York City-based study of stress in pregnancy started in 2009. When the children were approximately six years old, hormone levels were measured via their hair samples, electrocardiogram recordings were used to measure heart function during a stress-inducing condition, and behavioural and emotional functioning was assessed based on surveys administered to the parents.

The children of mothers who used cannabis during pregnancy showed higher anxiety, aggression, hyperactivity, and levels of the stress hormone cortisol, compared to children of non-cannabis users. Maternal cannabis use was also associated with a reduction in the high-frequency component of heart rate variability, which normally reflects increased stress sensitivity. In addition, RNA sequencing of placental tissue collected at birth in a subset of participants revealed that there was an association between maternal cannabis use and lower expression of immune-activating genes, including pro-inflammatory cytokines. The cannabis-related suppression of several placental immune-gene networks predicted higher anxiety in the children.

“Pregnant women are being bombarded with misinformation that cannabis is of no risk, while the reality is that cannabis is more potent today than it was even a few years ago. Our findings indicate that using it during pregnancy can have long-term impact on children,” said senior author Yasmin Hurd, PhD. “The study results underscore the need for nonbiased education and outreach to the public and particular vulnerable populations of pregnant women regarding the potential impact of cannabis use. Disseminating this data and accurate information is essential to improving the health of women and their children.”

Source: The Mount Sinai Hospital

Tranexamic Acid Cuts Blood Loss in Myomectomies

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The use of tranexamic acid (TXA) reduced blood loss during myomectomies in women with large uterine fibroids, a retrospective cohort study has found.

Patients who underwent a myomectomy to remove uterine fibroids with a total weight greater than 173 g had lower estimated blood loss after receiving TXA compared with those who did not (205.6 mL vs 405.4 mL), reported Rachel Cullifer, MD, at the virtual American Association of Gynecologic Laparoscopists (AAGL) annual meeting. Furthermore, patients whose largest fibroid was greater than 73 mm had lower levels of blood loss with TXA (229.2 mL vs 408.3 mL).

“TXA is a highly safe hemostatic agent that gynecologic surgeons can utilize during myomectomies,” Cullifer said. “There is a role for TXA in myomectomies performed with a minimally invasive approach,” she added, noting that the treatment should be strongly considered for patients suspected of having a large fibroid burden.

When looking at all myomectomies not stratified by fibroid characteristics, there was not no significant difference in estimated blood loss between patients who received TXA and those who did not (184 mL vs 266 mL). Fibroids are the primary indication for hysterectomy in the US, Dr Cullifer noted, but myomectomy provides a safe alternative for those who want to preserve their fertility.

“Despite advances in laparoscopic techniques, blood loss and blood transfusions still remain higher in myomectomies when compared with hysterectomy,” Dr Cullifer pointed out, adding that elevated plasmin levels during surgery can result in prolonged bleeding. TXA lowers plasmin function and productivity, reducing blood loss, she stated.

Dr Cullifer and colleagues focused on fibroid characteristics to find out which patients might benefit most from TXA.

The researchers analysed patients who had a myomectomy from 2015 to 2020, compared myomectomy cases treated with TXA versus those that were not, and measured estimated blood loss, blood transfusion administration, and operative time. Of the 71 patients who had a myomectomy, 26 received TXA and 45 did not. The average estimated blood loss was 236 mL, and almost all patients underwent minimally invasive procedures, with 53% undergoing laparoscopic surgery and 40% undergoing robot-assisted procedures.

Save for age, all demographic characteristics were similar between the two groups. Patients who received TXA were an average of two and a half years younger than those who did not. Fibroid characteristics were also similar between the two groups. Additionally, adverse events were similar between the two groups. There was one case of thromboembolism in the cohort who did not receive TXA.

Source: MedPage Today