Fertility News

Fertility takes up to eight months to return after stopping contraception

Fertility takes up to eight months to return after stopping contraception

Women may have to wait up for up to eight months for their fertility to return to normal after stopping some forms of contraceptives, new research suggests.

Oral contraceptives were, and still are, the most used method of contraception, but long-lasting reversible contraceptives, such as intrauterine devices (IUD) or injectable contraceptives are becoming more popular.

Previous studies had investigated the correlation between long-term oral contraceptive use and future chances of conceiving, finding no negative association, but there had been little research into other methods of contraception, and much of the research available is conflicting.

Run in collaboration between Boston University School of Public Health researchers and Aarhus University in Denmark, the study recruited 17,954 Danish and American women who had been trying to conceive for a minimum of six menstrual cycles over a twelve-year span. Of these women, 38 percent had recently used oral contraceptives, 31 percent used barrier methods and 13 percent used long-acting reversible contraceptives.

The study, published in the BMJ, used questionnaires to obtain data. Initial observations were collected on historical contraceptive use, and personal and lifestyle information. Follow-up questionnaires were then completed every two months for up to one year, or until the woman fell pregnant. Approximately 56 percent of women conceived within six menstrual cycles of stopping contraceptive use, and 77 percent within twelve menstrual cycles.

They found that the delay to fertility following cessation of contraceptives varied based on which contraceptive had been used.

Hormonal contraceptives were most likely to be associated with a delay in returning fertility, with the injectable hormone contraceptives taking the longest at five to eight cycles on average. Oral contraceptives took around three cycles, and IUDs and implant contraceptives took approximately two cycles. Interestingly, the delay to fertility was not impacted by how long the woman had been using her respective contraceptive, despite previous studies implicating a correlation.

Follow-up studies will be needed to corroborate these findings. Within the questionnaire, the researchers found that women taking the injectable hormones are more likely to have a higher body mass index, more likely to smoke and more likely to report a history of infertility; these could all be considered confounding factors as to why these women took longer to become pregnant. Furthermore, they relied on the woman’s estimation rather than a medical record for date of the last injection.

Nevertheless, the authors concluded: ‘Our results, although imprecise, indicate little or no lasting effect of long-term use of these methods on fecundability. […] These findings might inform clinical recommendations on contraceptive decision making’.

Read more: https://www.bmj.com/content/371/bmj.m3966

Source: https://www.bionews.org.uk/page_153206

New drug to treat female reproductive problems and improve fertility

New drug to treat female reproductive problems and improve fertility

A new drug that may be able to improve fertility for women with ovulatory problems has been showcased by researchers at Imperial College London.

The drug, called MVT-602, acts via the natural ‘kisspeptin‘ hormone system in the body. It modifies the activity of kisspeptin, making it more potent, stable and water-soluble.

Kisspeptin is an important reproductive hormone involved in the release of two other hormones from the pituitary gland – luteinizing hormone (LH) and follicle stimulating hormone (FSH) – that regulate maturation and release of egg cells.

‘This is the first study to show that a single dose of MVT-602 can induce a longer duration of hormonal stimulation in women than naturally occurring kisspeptin,’ said study author Dr Ali Abbara, National Institute for Health Research (NIHR) clinician scientist at Imperial College London. ‘Therefore, it reveals exciting potential to treat a range of reproductive health conditions using MVT-602 and offer women improved treatment options.’

Researchers carried out a trial at Hammersmith Hospital, part of Imperial College Healthcare NHS Trust, on 24 women aged 18-35 from 2017-2019. They were injected with the drug and their levels of LH and FSH were measured over several days.

Twelve of the women had no ovulatory problems; six had hypothalamic amenorrhea (HA), characterised by a lack of ovulation; and six had polycystic ovarian syndrome (PCOS), an endocrine disorder which presents with enlarged ovaries and irregular periods.

In addition, all of the healthy volunteers were given an injection of the naturally occurring kisspeptin (KP54) and saline placebo for comparison. The researchers then compared the women’s reproductive hormone levels after receiving MVT-602 to naturally occurring kisspeptin (KP54). They also compared the reproductive hormone levels after MVT-602 between healthy women, women with HA and those with PCOS.

The drug was able to stimulate a similar LH peak to kisspeptin alone in all groups, but showed a longer duration of action – with the peak remaining high for an extended time. A particularly strong response was observed in women with HA.

Previous work has shown that the naturally occurring form of kisspeptin-54 (KP54) is able to stimulate ovarian function for IVF treatment, without increasing the risk of ovarian hyperstimulation syndrome (OHSS).

However, the effect of kisspeptin is short-lasting and frequent administration reduces its effectiveness, limiting its applicability.

MVT-602 induced more potent signalling of the kisspeptin system over a longer period of time than KP54, according to researchers.

‘Our previous work showed that kisspeptin can be used to stimulate ovulation in women undergoing IVF treatment, but there are some limitations on using the naturally occurring kisspeptin hormone as its effectiveness wares off after a few hours,’ said lead author Professor Waljit Dhillo, research professor in endocrinology and metabolism at Imperial College London. ‘This study suggests that MVT-602 can stimulate kisspeptin over a longer period of time with no side effects, which means we could potentially use it to treat a wider range of reproductive disorders.

The researchers suggest that MVT-602 may be used to effectively treat a range of reproductive conditions that affect fertility such as polycystic ovary syndrome and hypothalamic amenorrhea.

Though promising, the findings are very early and experimental, far away from being used in clinical practice to help subfertile women with ovulatory problems.

Read more: https://www.jci.org/articles/view/139681

Source: https://www.bionews.org.uk/page_153326

System trained to detect highest quality IVF embryos outperformed trained embryologists

System trained to detect highest quality IVF embryos outperformed trained embryologists

In-vitro fertilization (IVF) can offer a life-changing solution to infertile couples. But the average success rate for IVF is about 30 percent.

Investigators from Brigham and Women’s Hospital and Massachusetts General Hospital are developing an artificial intelligence system with the goal of improving IVF success by helping embryologists objectively select embryos most likely to result in a healthy birth.

Using thousands of embryo image examples and deep-learning artificial intelligence (AI), the team developed a system that was able to differentiate and identify embryos with the highest potential for success significantly better than 15 experienced embryologists from five different fertility centers across the United States.

Results of their study are published in eLife.

“We believe that these systems will benefit clinical embryologists and patients,” said corresponding author Hadi Shafiee, PhD, of the Division of Engineering in Medicine at the Brigham. “A major challenge in the field is deciding on the embryos that need to be transferred during IVF. Our system has tremendous potential to improve clinical decision making and access to care.”

Currently, the tools available to embryologists are limited and expensive, and most embryologists must rely on their observational skills and expertise. Shafiee and colleagues are developing an assistive tool that can evaluate images captured using microscopes traditionally available at fertility centers.

“There is so much at stake for our patients with each IVF cycle. Embryologists make dozens of critical decisions that impact the success of a patient cycle. With assistance from our AI system, embryologists will be able to select the embryo that will result in a successful pregnancy better than ever before,” said co-lead author Charles Bormann, PhD, MGH IVF Laboratory director.

The team trained the AI system using images of embryos captured at 113 hours post-insemination. Among 742 embryos, the AI system was 90 percent accurate in choosing the most high-quality embryos.

The investigators further assessed the AI system’s ability to distinguish among high-quality embryos with the normal number of human chromosomes and compared the system’s performance to that of trained embryologists.

The system performed with an accuracy of approximately 75 percent while the embryologists performed with an average accuracy of 67 percent.

The authors note that in its current stage, this system is intended to act only as an assistive tool for embryologists to make judgments during embryo selection.

“Our approach has shown the potential of AI systems to be used in aiding embryologists to select the embryo with the highest implantation potential, especially amongst high-quality embryos,” said Manoj Kumar Kanakasabapathy, one of the co-lead authors.

Read more: https://elifesciences.org/articles/55301

Vitamin D levels in pregnancy linked with child IQ

Vitamin D levels in pregnancy linked with child IQ

Higher levels of vitamin D during pregnancy were linked to increased IQ in children.

Vitamin D is a critical nutrient and has many important functions in the body. A mother’s vitamin D supply is passed to her baby in utero and helps regulate processes including brain development.

A study published in The Journal of Nutrition showed that mothers’ vitamin D levels during pregnancy were associated with their children’s IQ, suggesting that higher vitamin D levels in pregnancy may lead to greater childhood IQ scores. The study also identified significantly lower levels of vitamin D levels among Black pregnant women.

Melissa Melough, the lead author of the study and research scientist in the Department of Child Health, Behavior, and Development at Seattle Children’s Research Institute, says vitamin D deficiency is common among the general population as well as pregnant women, but notes that Black women are at greater risk. Melough says she hopes the study will help health care providers address disparities among women of color and those who are at higher risk for vitamin D deficiency.

Melanin pigment protects the skin against sun damage, but by blocking UV rays, melanin also reduces vitamin D production in the skin. Because of this, we weren’t surprised to see high rates of vitamin D deficiency among Black pregnant women in our study. Even though many pregnant women take a prenatal vitamin, this may not correct an existing vitamin D deficiency,” Melough said.

I hope our work brings greater awareness to this problem, shows the long-lasting implications of prenatal vitamin D for the child and their neurocognitive development, and highlights that there are certain groups providers should be paying closer attention to. Wide-spread testing of vitamin D levels is not generally recommended, but I think health care providers should be looking out for those who are at higher risk, including Black women.”

Addressing disparities

According to Melough, as many as 80% of Black pregnant women in the U.S. may be deficient in vitamin D. Of the women who participated in the study, approximately 46% of the mothers were deficient in vitamin D during their pregnancy, and vitamin D levels were lower among Black women compared to White women.

Melough and her co-authors used data from a cohort in Tennessee called the Conditions Affecting Neurocognitive Development and Learning in Early Childhood (CANDLE) study. CANDLE researchers recruited pregnant women to join the study starting in 2006 and collected information over time about their children’s health and development.

After controlling for several other factors related to IQ, higher vitamin D levels in pregnancy were associated with higher IQ in children ages 4 to 6 years old. Although observational studies like this one cannot prove causation, Melough believes her findings have important implications and warrant further research.

Vitamin D deficiency

Vitamin D deficiency is quite prevalent,” Melough said. “The good news is there is a relatively easy solution. It can be difficult to get adequate vitamin D through diet, and not everyone can make up for this gap through sun exposure, so a good solution is to take a supplement.”

The recommended daily intake of vitamin D is 600 international units (IU). On average, Americans consume less than 200 IU in their diet, and so if people aren’t making up that gap through sun exposure or supplementation, Melough says people will probably become deficient. Foods that contain higher levels of vitamin D include fatty fish, eggs and fortified sources like cow’s milk and breakfast cereals. However, Melough notes that vitamin D is one of the most difficult nutrients to get in adequate amounts from our diets.

Additional research is needed to determine the optimal levels of vitamin D in pregnancy, but Melough hopes this study will help to develop nutritional recommendations for pregnant women.

Read more: https://academic.oup.com/jn/advance-article-abstract/doi/10.1093/jn/nxaa309/5951845?redirectedFrom=fulltext

Sperm biomarker associated with couples’ pregnancy probability

Sperm biomarker associated with couples’ pregnancy probability

Researchers at the University of Massachusetts Amherst have identified a single-measure biomarker in sperm mitochondrial DNA that may predict male reproductive health and pregnancy success.

The discovery applies not just to couples seeking care for infertility but also for the general population. This biomarker could become a more accurate predictor of male infertility than semen parameters, on which health care organizations and clinicians have long relied.

“Clinically, the diagnosis of male infertility really hasn’t changed in decades,” says UMass Amherst environmental epigeneticist Richard Pilsner, corresponding author of the study published in the journal Human Reproduction. “In the last 10 to 20 years, there have been major advances in the understanding of the molecular and cellular functions of sperm, but the clinical diagnosis hasn’t changed or caught up.”

“This project is a really nice example of interdisciplinary work and team science,” Brian Whitcomb, associate professor of epidemiology in the School of Public Health and Health Sciences says. “This research required measurement of biomarkers in the laboratory combined with statistical modeling. Answering scientific questions like this one benefits from a broad range of expertise.”

Mitochondrial DNA is maternally inherited, and sperm mitochondrial DNA copy number (mtDNAcn) typically decreases eight-to-10 fold during spermatogenesis to ensure that it is low upon fertilization.

In previous research increased mtDNAcn and mitochondrial DNA deletions (mtDNAdel) were associated with decreased semen quality and lower odds of fertilization in men seeking fertility treatment.

“The logical next step was to determine if the associations between sperm mitochondrial biomarkers and fertilization among couples seeking infertility treatment could be extended to couples from the general population” according to researchers.

The researchers accessed sperm samples from the Longitudinal Investigation of Fertility and the Environment (LIFE) study, which recruited 501 couples from Michigan and Texas from 2005 to 2009 to examine the relationships between lifestyle, including environmental chemicals, and human fertility.

They assessed sperm mtDNAcn and mtDNAdel from 384 semen samples and analyzed their association with the probability of pregnancy within one year. They found that men with higher sperm mtDNAcn had as much as 50% lower odds of cycle-specific pregnancy and 18% lower probability of pregnancy within 12 months.

“Remarkably, we saw a strong inverse association between sperm mitochondrial biomarkers and couples’ time-to-pregnancy,” the researchers said. Mitochondrial DNA in sperm seems to reflect some underlying physiological phenomenon that affects sperm function.”

More research is needed to further examine the impact of changes in mtDNAcn and mtDNAdel, which may result from defective mitochondria or damaged mtDNA.

A next step is to examine the factors mediating the changes in sperm mitochondrial DNA. They could include environmental toxins or other causes of inflammation and oxidative stress, the scientists hypothesize.

“Understanding what is causing the retention of mitochondrial copy number during spermatogenesis will help us come up with better platforms to intervene and to promote better reproductive success,” according to the researchers.

Read more: https://academic.oup.com/humrep/advance-article-abstract/doi/10.1093/humrep/deaa191/5918336?redirectedFrom=fulltext

Source: https://www.sciencedaily.com/releases/2020/10/201006091224.htm

Delivering proteins to testes could someday treat male infertility

Delivering proteins to testes could someday treat male infertility

Researchers have found a way to deliver a protein important for sperm cell production directly to mouse testicles, where it restored normal sperm development and allowed previously infertile mice to father pups.

Male infertility often happens because of a lack of sperm in the semen, which can result from damage to the blood-testis barrier (BTB). This barrier protects reproductive cells from harmful toxicants and drugs, and a protein called PIN1 is important for its function.

Knockout of Pin1, an important regulator of cell proliferation and differentiation, produces male infertility phenotypes such as testicular immaturity and azoospermia with spermatogonia depletion and blood–testis barrier (BTB) dysfunction.

Mice genetically engineered to lack PIN1 are infertile, with small testes, depleted sperm stem cells and a low sperm count. Although scientists have considered gene therapies to treat male infertility, these procedures are risky because they could cause unwanted genetic changes in reproductive cells that might be passed onto offspring.

Hyun-Mo Ryoo and colleagues wanted to develop a system to deliver proteins (such as PIN1) instead of genes to the testes, but first they had to find a way to get proteins through the complex tubes of the testicles and into cells.

The researchers developed a delivery system called Fibroplex, which consisted of spherical nanoparticles made of silk fibroin and a coating of lipids. They loaded PIN1 into Fibroplex, and showed that the particles appeared safe and didn’t show signs of toxicity or testicular damage in mice. When the team injected the PIN1-loaded Fibroplex into the testes of young mice with PIN1 deletions, the treatment restored nearly normal PIN1 levels and sperm stem cell numbers and repaired the BTB.

Treated mice had normal testicular weight and size and about 50% of the sperm count of wild-type mice. Until about 5 months after treatment, when the protein degraded, the PIN1-Fibroplex-treated mice fathered a similar number of pups as wild-type mice, whereas untreated mice with PIN1 deletions remained infertile.

This is the first demonstration of direct delivery of proteins into the testis to treat male infertility, the researchers say.

Read more: https://pubs.acs.org/doi/10.1021/acsnano.0c04936

Source: www.sciencedaily.com/releases/2020/10/201021130145.htm

COVID-19 leads to more women freezing their eggs

COVID-19 leads to more women freezing their eggs

Fertility clinics have seen a sharp rise in the number of women inquiring about egg freezing – up to 50 percent more inquiries at some clinics.

They have reported that for many of these women, the lockdown has triggered a period of reflection over their parental future, particularly given that opportunities to meet a partner have been greatly reduced.

Kate Davidson from Cheltenham, who is 35 and single, told the Sunday Times: ‘A big part of me wanted to do it because I wanted to share my eggs… But I also like the fact that I’ve got some put away for me now. I was quite reflective about work, life – all those things. I think that’s what prompted me to make the move.’

‘The whole way in which we socialise and date has changed… if I don’t meet the man of my dreams until I’m 39, then at least I know I’ve got the eggs of a 33-year-old’ said a woman named only as Katherine, in the same article. ‘I just haven’t met that person, and with the coronavirus, I felt that it was becoming harder. That was the trigger.’

Compared with last summer, both Create Fertility and The London Women’s Clinic have seen consultations for egg freezing rise by 25 percent, while the King’s Fertility and Harley Street Fertility Clinics reported rises of 15 and 20 percent respectively.

‘Social’ egg freezing refers to patients who choose to preserve their fertility for lifestyle rather than medical reasons and is only available privately.

A recent report by the Human Fertilisation and Embryology Authority showed that the number of women opting to freeze their eggs or embryos in the UK rose 523 percent between 2013 and 2018.

Professor Joyce Harper, professor of reproductive science at University College London, said: ‘The majority of women who freeze their eggs… are single. When they’ve been asked, most of them want to have children now, they just haven’t met Mr Right or haven’t got a partner who is happy to have children.’

Currently, UK law prevents eggs frozen for non-medical reasons to remain in storage for more than ten years. A recent report from the Nuffield Council on Bioethics joined other voices in the field in calling for this limit to be removed.

Sarah Norcross, director of the Progress Educational Trust, said ‘With more women than ever choosing to freeze their eggs, it is time for the law to be changed’.

Source: https://www.bionews.org.uk/page_152631

Pregnancy complications linked to heightened risk of heart disease and stroke in later life

Pregnancy complications linked to heightened risk of heart disease and stroke in later life

Pregnancy complications such as miscarriage, pre-eclampsia, diabetes in pregnancy (gestational diabetes) and pre-term birth are linked to a heightened risk of heart disease in later life, suggests an overarching (umbrella) analysis of data.

Several other factors related to fertility and pregnancy also seem to be associated with subsequent cardiovascular disease, say the researchers, including starting periods early, use of combined oral contraceptives, polycystic ovary syndrome, and early menopause.

However, a longer length of breastfeeding was associated with a reduced risk of cardiovascular disease.

Previous research has suggested that risk factors specific to women may be linked to cardiovascular disease and stroke, but clarity on the quality of the evidence is lacking and on how the findings can be translated into public health and clinical practice.

So a team of UK researchers searched relevant research databases for published systematic reviews and meta-analyses that investigated links between reproductive factors in women of reproductive age and their subsequent risk of cardiovascular disease.

A total of 32 reviews were included, evaluating multiple risk factors over an average follow-up period of 7-10 years.

The researchers found that several factors, including starting periods early (early menarche), use of combined oral contraceptives, polycystic ovary syndrome, miscarriage, stillbirth, pre-eclampsia, diabetes during pregnancy, pre-term birth, low birth weight, and early menopause were associated with an up to twofold risk of cardiovascular outcomes.

Pre-eclampsia was associated with a fourfold risk of heart failure.

Possible explanations for these associations include family medical history, genetics, weight, high blood pressure and cholesterol levels, and chemical imbalances from use of hormonal contraceptives.

However, no association was found between cardiovascular disease outcomes and current use of progesterone only contraceptives, use of non-oral hormonal contraceptive agents, or fertility treatment.

What’s more, breastfeeding was associated with a lower risk of cardiovascular disease.

The researchers point to some limitations, such as missing data and the fact that reviews were largely based on observational evidence, so they cannot rule out the possibility that other unmeasured (confounding) factors may have had an effect.

Nevertheless, they say the evidence reported in this umbrella review suggests that, from menarche to menopause, the reproductive profile of women is associated with their future risk of cardiovascular disease.

It also provides clarity on the quality of the evidence, identifies gaps in evidence and practice, and provides recommendations that could be incorporated into guidelines, such as incorporating reproductive risk factors as part of the risk assessment for cardiovascular disease, they conclude.

Read more: https://www.bmj.com/content/371/bmj.m3502

Placenta is the first organ to form in a fertilised egg

Placenta is the first organ to form in a fertilised egg

Placenta development is initiated first in human pregnancies, even before the embryo starts to form, according to new research.

A team of scientists at the Francis Crick Institute, London, has found that one of the first steps after egg fertilisation in mammals is the initiation of placenta creation, the organ responsible for providing oxygen and nutrients to the growing baby.

‘This study highlights the critical importance of the placenta for healthy human development,’ said Dr Kathy Niakan, senior author of the study and group leader at the Crick. ‘If the molecular mechanism we discovered for this first cell decision in humans is not appropriately established, this will have significant negative consequences for the development of the embryo and its ability to successfully implant in the womb.’

Once an egg is fertilised the cell rapidly divides and a key process called cell specialisation occurs, where each cell is assigned a specific task.

The team sought to examine the very first cell specialisations by studying donated human embryos that were surplus to in vitro fertilisation (IVF) treatment.

In embryos at the 16-32 cell stage, the team observed a subset of cells which changed shape and polarised, this triggered molecular events that drives placenta specialisation. In particular, atypical protein kinase C (aPKC) was highly expressed at one end of the cell, when aPKC was inhibited the cells no longer became placenta precursors.

This first cell specification is ‘widespread in mammals’ said researchers after they found the same result in cow and mouse embryos, which have divergent mechanisms at later stages of development.

This research, published in Nature, revealed that placenta development starts much earlier than previously thought, before the embryo has implanted into the wall of the uterus, suggesting placenta cells may have important functions in healthy embryo implantation and development.

During IVF treatment, a reliable predictor of successful implantation of an embryo is the presence of placental precursor cells under the microscope. Therefore, this work paves the way towards a better understanding of how to help those struggling to conceive.

‘Understanding the process of early human development in the womb could provide us with insights that may lead to improvements in IVF success rates in the future’ adds Dr Niakan, ‘It could also allow us to understand early placental dysfunctions that can pose a risk to human health later in pregnancy.’

Read more: https://www.nature.com/articles/s41586-020-2759-x

Source: https://www.bionews.org.uk/page_152173

COVID-19 could cause male infertility

COVID-19 could cause male infertility

Males who suffer from moderate or severe cases of COVID-19 could experience reduced fertility, according to a new study conducted by Dr. Dan Aderka of Sheba Medical Center.

Aderka reported that not only was the virus found within the sperm of some 13% of screened male COVID-19 patients, but that there was a 50% decrease in the sperm volume, concentration and motility in patients with moderate disease even 30 days post diagnosis.

Post-mortem tests of 12 COVID-19 patients demonstrated moderate to severe changes in the testicular cells supporting sperm development and those producing testosterone, the hormone that induces sperm division and multiplication.

Aderka, whose article was published in the medical journal Fertility and Sterility, told The Jerusalem Post that the cause for this phenomenon seems to be the presence of the ACE2 receptor on the surface the cell of the Sertoli and Leydig cells of the testis, the same receptors on the cells of lungs, kidneys and hearts.

The Sertoli cells support sperm maturation. The Leydig cells produce testosterone.

He said the coronavirus binds to the ACE2 receptors and destroys the cells, which causes infertility.

As normal sperm maturation takes 70 to 75 days, it is possible that if we are doing a sperm examination two and a half months after recovery, we may see even more reduced fertility,” Aderka said. “It could be even more detrimental.”

He added that it is also still unclear if the effects on the quality and quantity of the sperm are reversible or persistent. He said doctors will need to examine these same patients six months and a year after recovery to see if the damage “stands the test of time.” This is something his team is planning to do.

Aderka said that there is another hypothesis that can now be explored, also as a result of his research: “Interestingly, an enzyme called TMPRSS2 assists the virus in binding to the ACE receptor, facilitating its internalization into the cells.”

TMPRSS2 is activated by testosterone.

This phenomenon may explain the higher COVID-19 morbidity and mortality of men compared to women,” he told the Post, adding that it also may explain the lower morbidity and mortality of children, whose testosterone levels are low.

Source: https://www.jpost.com/health-science/covid-19-could-cause-infertility-new-israeli-study-644767

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