Category: Obstetrics & Gynaecology

A Keto Diet may Improve Fertility in Women with PCOS

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The ketogenic (keto) diet may lower testosterone levels in women with polycystic ovary syndrome (PCOS), according to a new paper published in the Journal of the Endocrine Society. The diet also appeared to lower follicle-stimulating hormone (FSH) levels, which may thereby improve the chances of ovulating. These improvements in hormonal balance could help alleviate fertility problems.

PCOS is the most common hormone disorder in women, affecting 7–10% of women of childbearing age. It can cause infertility and raises the risk of developing diabetes, obesity and other metabolic health problems.

Women with PCOS have at least two of these signs:

  • Elevated levels of testosterone and other androgen hormones associated with male reproduction,
  • Irregular periods, and
  • Large ovaries with many small follicles.

The keto diet is a high fat, low carbohydrate diet that has shown promising effects in women with PCOS. Studies have shown that it may help women lose weight and maintain weight loss, improve their fertility, optimise their cholesterol levels and normalise their menstrual cycles.

“We found an association between the ketogenic diet and an improvement in reproductive hormone levels, which influence fertility, in women with PCOS,” said study author Karniza Khalid, MBBS, MMedSc, of the Ministry of Health Malaysia in Kuala Lumpur, Malaysia. “These findings have important clinical implications, especially for endocrinologists, gynaecologists and dieticians who, in addition to medical treatment, should carefully plan and customise individual diet recommendations for women with PCOS.”

The researchers conducted a meta-analysis of clinical trials in women with PCOS on the keto diet and examined the diet’s effects on their reproductive hormones (FSH, testosterone and progesterone) and weight change.

They found women with PCOS who were on the keto diet for at least 45 days saw significant weight loss and an improvement in their reproductive hormone levels. Their FSH ratio was lower, which means they may have a better chance of ovulating. The women also had lower testosterone levels, which could help with excess hair growth and other symptoms of excess male sex hormones.

Source: The Endocrine Society

Before Birth, Substance Use by Father can Also Increase Risk of Intellectual Disability for Child

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Children of a parent with alcohol or drug use disorder have a greater risk of intellectual disability, even if the problem only lies with the father, researchers from Karolinska Institutet report. According to the study, which is published in the journal eClinicalMedicine, preventive measures should be directed at both parents.

A woman’s consumption of alcohol during pregnancy has been well established as increasing the risk of the child developing. Research from Karolinska Institutet now shows that all forms of substance abuse, both in the mother and the father, and not only during pregnancy, can constitute a risk factor.

Previous efforts aimed at mothers

“Preventative measures, such as educating healthcare professionals and public health recommendations, have focused for decades on mothers with alcohol-related problems,” says Lotfi Khemiri, researcher at Karolinska Institutet. “Our findings highlight the importance of also directing such measures towards fathers with different types of substance use disorder.”

The study drew on data from Swedish registries with almost two million babies born between 1978 and 2002 and their parents. The researchers found that 1.2% of babies born to parents without such a disorder were diagnosed with an intellectual disability, compared with 3% of the babies who had one parent with a diagnosis related to a substance use disorder (alcohol or drug abuse).

Higher risk before birth

The elevated risk was greater if the parent had received a diagnosis before or during pregnancy rather than after birth. A substance use disorder diagnosis registered before birth was associated with more than twice the risk of intellectual disability in the baby, regardless of which parent had the diagnosis. The correlation was weaker but still statistically significant after adjustment of socioeconomic factors and psychiatric comorbidity in the parents.

“Since it was an observational study, we can draw no conclusions about the underlying mechanism, but we suspect that both genetic and environmental factors, including harmful effects of substance abuse on foetal development, may play a part,” says Dr Khemiri. “We hope that the results will contribute to the preventative efforts, as well as to the improved diagnosis of children with an intellectual disability and to timely intervention directed both to the child as well as parents in need of substance use disorder treatment.”

Alcohol a major risk factor

Intellectual disability was observed to be much more likely in alcohol-related problems during pregnancy, where the risk was five and three times higher depending on whether it was the mother or father who had the alcohol use disorder diagnosis.

Source: Karolinska Institutet

Lactobacillus Combo Stops Bacteria that Cause Toxic Shock Syndrome

Methicillin resistant Staphylococcus aureus (MRSA) – Credit: CDC

A virulent strain of Staphylococcus aureus produces proteins that trigger toxic shock syndrome (TSS), a disease characterised by the quick onset of fever, a telltale rash, and, without treatment, multi organ failure. In the vagina, TSS is associated with a life-threatening reaction from the immune system. Research published in the journal Microbiology Spectrum shows that probiotics may help prevent the disease before the cytokine cascade ever begins.

Probiotics may help prevent the disease before the cytokine cascade ever begins. This study reports that strains of two bacteria, Lactobacillus acidophilus and Lacticaseibacillus rhamnosus, successfully inhibited the production of the superantigens that cause TSS, in lab experiments. L. acidophilus, in addition, inhibited the growth of the S. aureus strains that produce the problematic proteins.

A combination of the two could both prevent growth and inhibit the immune response. “It’s kind of a double whammy against S. aureus,” said microbiologist Patrick Schlievert, Ph.D., at the University of Iowa Carver College of Medicine, in Iowa City. “If any toxin is made, the probiotics still prevent inflammation.”

He noted that adding these probiotics to tampons or other menstrual products could reduce the risk of TSS associated with menstruation. Such a preventive measure has the potential to benefit millions of vulnerable people, Schlievert said. “We know that 20% of people over age 12 cannot make antibodies and never will make antibodies against toxic shock syndrome,” he said.

Schlievert has been studying TSS and its prevention for decades. In the early 1980s, he was the first researcher to identify the toxin that triggers an overreaction of the immune system, and to show how high-absorbency tampons facilitated production of that toxin if S. aureus was present.

The new work, he said, was motivated by observations made during an earlier study. A few years ago, he and his colleagues recruited 205 women to test whether a novel molecular mixture, when added to tampons, would inhibit pathogenic bacteria. That molecule proved effective against E. coli and other pathogens, but the researchers noticed an unexpected consequence.

“Some of the women in the treatment group had this tremendous growth of Lactobacilli,” Schlievert said.

Source: American Society for Microbiology

Cadmium Detected in Urine of Women with Endometriosis

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Women with a history of endometriosis had higher concentrations of cadmium in their urine compared to those without that diagnosis, according to a study with a large representative study that suggests the toxic metal, which is also an endocrine disruptor, could be linked to the development of endometriosis. The researchers, from Michigan State University, published these findings in the journal Human Reproduction.

Affecting one in 10 reproductive-age women, endometriosis is when tissue that looks like the lining of the uterus, appears outside of it. Those with endometriosis can experience chronic, painful and debilitating symptoms, which can interfere with all aspects of life, including daily activity, work productivity, school performance and personal relationships.

“Despite the adverse impact of endometriosis on quality of life, it remains an understudied condition,” said Kristen Upson, assistant professor in the Department of Epidemiology and Biostatistics at the MSU College of Human Medicine and senior author of the study.

“By looking at environmental risk factors such as metal cadmium, we are moving the needle closer to understanding risk factors for this condition,” added the study’s first author, Mandy Hall, a data analyst in the MSU Department of Epidemiology and Biostatistics.

Cadmium is a toxic metal and a “metalloestrogen,” meaning it can act like oestrogen. In the US, people are commonly exposed to cadmium by breathing in cigarette smoke and eating contaminated food like spinach and lettuce.

While this is not the first study exploring a potential link between cadmium and endometriosis, the researchers said it’s the largest study to look at cadmium measured in urine, which reflects long-term exposure between 10 and 30 years.

For their study, researchers used data from NHANES, a national US population study between 1999 and 2006. Out of the survey’s more than 41 000 participants, the researchers limited their study population to those 20 to 54 years of age with information on endometriosis diagnosis.

The researchers then analysed the data, dividing the cadmium levels into four classes, or quartiles, with the first quartile being the lowest exposure and the fourth being the largest exposure.

They found that participants in the second and third quartiles were twice as likely to have been diagnosed with endometriosis than those in the first quartile. The data also suggests a 60% increased prevalence of endometriosis based on urinary cadmium concentrations in the fourth quartile.

“The findings are interesting given that cadmium can act like the hormone estrogen, and this hormone is central to the development of endometriosis,” Hall said.

The researchers say further studies are needed to confirm their findings. Upson said this work is part of her larger research looking at everyday factors that may increase toxic metal exposure in women as well as the impact of toxic metals on gynaecologic health. Hall plans to incorporate environmental factors in their ongoing research on endometriosis and other gynaecologic conditions.

Source: Michigan State University

Green Tea Extract may Reduce Uterine Fibroids

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In a pre-clinical, proof-of-concept study from Johns Hopkins Medicine, researchers found that epigallocatechin gallate (EGCG), a green tea compound with powerful antioxidant properties, could be promising for both treating and preventing uterine fibroids. Results of the study, appearing in Scientific Reports, add to growing evidence that EGCG may reduce fibroid cell growth, though the study is still at an early stage. The study was specifically designed to identify the biochemical mechanisms responsible for EGCG action in fibroid cells.

The investigators emphasise that their study involves in vitro human fibroid cells treated with EGCG extract to explore the possibility of oral EGCG supplementation as a therapy, rather than just drinking cups of green tea as a preventative measure for uterine fibroids.

“The purpose of this study was to examine how EGCG works to treat and prevent uterine fibroids,” says James Segars Jr., MD, professor of gynaecology and obstetrics. “There is no standard protocol for uterine fibroid disease management or prevention, no tools to prevent their growth, so finding a safe nonsurgical therapy is important.”

Uterine fibroids are the most common benign tumours of the uterus. Made up of smooth muscle cells and a large matrix of connective tissue, the fibroids range in size from nearly microscopic to bulky masses that can enlarge and distort the uterus.

An estimated 77% of women will develop fibroids in their lifetime, most of them by age 50. Black and Hispanic women develop them at 1.5 to two times the rate of white women.

While many people with uterine fibroids are symptom-free, about 25% experience significant symptoms including heavy uterine bleeding, pelvic pain and infertility. In addition to complete removal of the uterus, surgical treatment may include various means of removing fibroid tumours from the uterine wall.

For the new study, researchers used laboratory cultures of uterine fibroids collected from living patients. Because uterine fibroid cells have a large extracellular matrix compared to normal cells, researchers designed their experiments to see if treatment of cells with EGCG affects protein expression associated with this matrix. Specifically, they studied fibronectin, a matrix protein; cyclin D1, a protein involved with cell division; and connective tissue growth factor (CTGF) protein.

Cells were dosed with 100mmol/L of EGCG in growth media for 24 hours, and then a Western blot was performed. In this study, researchers looked for levels of cyclin D1 and CTGF proteins in EGCG-treated fibroid cells compared to untreated cell.

They found that EGCG reduced protein levels of fibronectin by 46% to 52%, compared with an untreated controls. They also found that EGCG disrupted pathways involved in fibroid tumour cell growth, movement, signalling and metabolism, and they saw up to an 86% decrease in CTGF proteins compared with the control group.

“The results from this study show that EGCG targets many signalling pathways involved in fibroid growth, particularly the extracellular matrix,” says study lead author Md Soriful Islam, PhD, MSc. “EGCG supplements could be an easily accessible and natural way to relieve symptoms and slow fibroid growth.”

These results lend support to the FRIEND study, an ongoing clinical trial of EGCG in women with fibroids who are seeking pregnancy. While results from this study show promise, researchers caution that more studies need to be done, and consumers should not try to self-dose with green tea supplements. Future research on EGCG will include clinical trials with large and diverse patient groups to determine optimal doses as well as possible side effects of EGCG supplementation.

Source: John Hopkins Medicine

Multidisciplinary Approach Reduced Hypothermia in NICU Babies During and After Surgery

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After implementation of a multidisciplinary quality improvement project, the percentage of infants from the neonatal intensive care unit (NICU) experiencing hypothermia upon operating room (OR) arrival and at any point during the operation decreased from 48.7% to 6.4% and 67.5% to 37.4%, respectively. Conducted at Ann & Robert H. Lurie Children’s Hospital of Chicago, the successful project and was featured in the journal Pediatric Quality and Safety.

About one-third of infants admitted to children’s hospitals’ NICUs require surgery and are at increased risk for intraoperative hypothermia due to environmental heat loss, anaesthesia, and inconsistent temperature monitoring. Hypothermic infants are at risk for infection, excessive bleeding, increased oxygen consumption, the need for cardiorespiratory support, and mortality.

Upon return to the NICU, the percentage of infants experiencing postoperative hypothermia decreased from 5.8% to 2.1% while postoperative hyperthermia increased from 0.8% to 2.6%.

“Intraoperative hypothermia is more prevalent than postoperative hypothermia, yet the problem appears to be recognized less. Several improvement projects have addressed postoperative hypothermia, however, few have focused on reducing intraoperative hypothermia,” said senior author Gustave Falciglia, MD, MSCI, MSHQPS, neonatologist at Lurie Children’s. “The strengths of our project were the large cohort of infants and the use of continuous, secure and automated data to ensure normal temperature for infants before, during and after an operation. Using our current approach, however, further decreasing intraoperative and postoperative hypothermia may not be possible without further increasing postoperative hyperthermia.”

Dr Falciglia and colleagues from Lurie Children’s Center for Quality and Safety, anaesthesiology, NICU and OR nursing, surgery, neonatology and Data Analytics and Reporting succeeded in reducing rates of intraoperative hypothermia by standardising temperature monitoring, the transport process to the OR and intraoperative warming.

“In this project, we used improvement science methodology to understand the barriers to maintaining normal temperature in NICU infants before, during and after surgery, and then to design and implement solutions,” said lead author Abbey Studer from the Center for Quality and Safety at Lurie Children’s. “We found variation in processes that contributed to intraoperative hypothermia, so we focused on standardizing temperature monitoring and thermal support during the infant’s transport and operation. Automated monitoring using a preoperatively placed continuous temperature probe enhanced providers’ situational awareness of infant temperature and guided clinical adjustments.”

For this improvement project, the hospital’s Center for Quality and Safety coordinated care and resources between multiple departments. It achieved consensus and buy-in from providers despite competing factors such as perspiring surgeons and busy anaesthesia providers transporting all infants to the OR. It identified key participants who were vested in revising processes and facilitated adoption with their colleagues, following up on missed opportunities and gaps in the processes identified through observation and surveys. The centre provided data analysts who worked iteratively with providers to generate valid, actionable, and real-time data.

“Although medicine prizes specialisation, our success relied upon individuals with various talents sharing their skills and knowledge,” said Dr Falciglia. “Working together we can continue to improve the care of infants in the NICU who need surgery.”

Source: Ann & Robert H. Lurie Children’s Hospital of Chicago

Researchers Discover a Lipid Biomarker that can Identify Preeclampsia Risk

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University of Virginia School of Medicine researchers have discovered a lipid biomarker to identify pregnant women at risk of preeclampsia, complications from which are the second-leading cause of maternal death around the world. Their findings are published in the Journal of Lipid Research.

The UVA scientists, led by Charles E. Chalfant, PhD, say that their finding opens the door to simple blood tests to screen patients. Further, the approach worked regardless of whether the women were on aspirin therapy, which is commonly prescribed to women thought to be at risk.

“Clinicians have been seeking simple tests to predict risk of preeclampsia before symptoms appear. Although alterations in some blood lipid levels have been known to occur in preeclampsia, they have not been endorsed as useful biomarkers. Our study presents the first comprehensive analysis of lipid species, yielding a distinctive profile associated with the development of preeclampsia,” said Chalfant. “The lipid ‘signature’ we described could significantly improve the ability to identify patients needing preventative treatment, like aspirin, or more careful monitoring for early signs of disease so that treatment could be initiated in a timely fashion.”

Preeclampsia affects up to 7% of all pregnancies. Symptoms typically appear after 20 weeks and include high blood pressure, kidney problems and abnormalties in blood clotting. The condition is associated with dangerous complications such as kidney and liver dysfunction and seizures, as well as a lifelong increased risk of heart disease for the mothers. An estimated 70 000 women around the world die from preeclampsia and its complications each year.

Doctors commonly recommend low-dose aspirin for at-risk women, but it works for only about half of patients, and it needs to be started within the first 16 weeks of pregnancy – well before symptoms appear. That makes it all the more important to identify women at risk early on, and to better understand preeclampsia in general.

Chalfant and his team wanted to find ‘biomarkers’ in the blood of pregnant women that could reveal their risk of developing preeclampsia. They examined blood plasma samples collected from 57 women in their first 24 weeks of pregnancy, then looked at whether the women went on to develop preeclampsia. The researchers found significant differences in ‘bioactive’ lipids in the blood of women who developed preeclampsia and those who did not.

This, the researchers say, should allow doctors to stratify women’s risk of developing preeclampsia by measuring lipid changes in their blood. The changes represent an important ‘lipid fingerprint’, the scientists say, that could be a useful tool for identifying, preventing and better treating preeclampsia.

“The application of our comprehensive lipid profiling method to routine obstetrical care could significantly reduce maternal and neonatal morbidity and mortality,” Chalfant said. “It represents an example of how personalised medicine could address a significant public health challenge.”

Source: University of Virginia Health System

B Cells Are Elevated in PCOS – But Are not The Cause

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While previous research have shown that while more B cells are present in women in polycystic ovary syndrome (PCOS), a new study by researchers at Karolinska Institutet has ruled out B cells as the cause of this common syndrome. The study is published in eLife.

Affecting 10–15% of women of fertile age, PCOS is linked to irregular ovulation and menstruation, pregnancy complications, and insulin resistance, all of which are worsened by being overweight. PCOS increases with rising body mass index, and in women with severe obesity, it is around 25%. While the root cause of the condition is unknown, a driver is a surplus of androgens.  

A recent study has shown that women with PCOS have a higher number of B cells in their blood and proposed that these contribute to the development of PCOS through the production of autoimmune antibodies.

“We’ve now examined how B cells affect the development of PCOS with the goal to find new ways of treating the conditions,” says the study’s last author Elisabet Stener-Victorin, research group leader for reproductive endocrinology and metabolism at the Department of Physiology and Pharmacology at Karolinska Institutet.

First, blood from women with PCOS was examined and showed abnormal variations in the frequency of different populations of B cells compared to healthy women. Among these were the so called double negative B cells, a heterogeneous cluster, where some have been described as poised to develop autoimmune functions.

To study whether B cells may cause PCOS, the researchers transferred antibodies from women with PCOS to mice to see if they developed the syndrome. While this proved not to be the case, they did put on weight.

Mice unaffected by B cells

The next step was to transfer B cells from PCOS-like mice (induced by continuous exposure to androgens) to mice lacking B cells to test the hypothesis that B cells drive the development of the disease. However, the recipient mice were unaffected by this transfer.

To see if B cells play an essential role in the development of PCOS, mice lacking B cells were exposed to androgens. These mice were not protected as expected, but developed the same characteristics as normal mice acquire when exposed to androgens.

Finally, androgen exposed PCOS-like mice displayed altered B cell frequencies, as women with PCOS, and simultaneous treatment with a drug that blocks androgen receptors, prevents these alterations of B cells in both blood and tissues, such as ovaries and endometrium.

The researchers conclude that androgens are necessary for the condition to form, but not B cells, the role of which remains unclear.

“B cells are clearly affected in the syndrome, which could contribute to a higher susceptibility to some comorbidities, but they don’t cause PCOS,” says Sara Torstensson, PhD student at Institutet and shared first author.

“We are now studying how other immune cells are affected and how this influences reproductive and metabolic function in PCOS,” says Angelo Ascani, guest PhD student at Graz University, Austria and also first author.

Source: Karolinska Institutet

Foetal Exposure to THC could Lead to Long-lasting Health Impacts

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Consuming THC (Delta-9-tetrahydrocannabinol) while pregnant could potentially affect development of the foetus and lead to life-long health impacts for offspring, according to a new study published in the journal Clinical Epigenetics.

THC is the main psychoactive ingredient in cannabis, which is growing in popularity and availability. The prevalence of cannabis use in pregnancy is also rapidly increasing, especially during the first trimester, when the foetus is most vulnerable to environmental exposures, to mitigate common symptoms like morning sickness. However, the potential effects of prenatal cannabis use on foetal development remain inconclusive, in part due to a lack of safety data. This study aimed to identify the potential long-term health impacts of THC use during pregnancy.

In a non-human primate model, Oregon Health & Science University researchers found that exposing a pregnant subject to THC altered placental and foetal epigenetics. Researchers also found that that these changes to gene regulation and expression are consistent with those seen with many common neurobehavioural conditions, including autism spectrum disorder.

“Cannabis is one of the most commonly used drugs and is widely available across the country, so there is a common perception that its completely safe to use,” said the study’s lead author Lyndsey Shorey-Kendrick, PhD, a computational biologist in the Division of Neurosciences at OHSU’s Oregon National Primate Research Center, or ONPRC. “The reality is that cannabis still carries many health risks for certain populations, including those who are pregnant. If we’re able to better understand the impacts, we can more effectively communicate the risks to patients and support safer habits during the vulnerable prenatal period.”

In a model using nonhuman primates, researchers administered THC in a daily edible and compared its effects to a group receiving a placebo. Specifically, researchers evaluated the epigenetic changes in several key areas that indicate healthy prenatal development: the placenta and foetal lung, brain and heart.

When looking at these areas, analyses showed that THC exposure altered the epigenome, meaning a process in which the information encoded in a gene is turned into a function or observable trait. Genes are all specifically coded to contribute to different functions of the body and brain, so any impact on epigenetic processes due to drug exposure is concerning, especially during a critical developmental window such as pregnancy.

Researchers found that significant changes involved genes associated with common neurobehavioral disorders, including autism spectrum disorder and attention deficit hyperactivity disorder. These conditions are linked to adverse health outcomes in childhood and adolescence, including poorer memory and verbal reasoning skills, and increased hyperactivity, impulsivity and inattention.

The research team hopes findings from this study will add to the limited existing literature on THC use during pregnancy, and help guide patient counselling and public health polices focused on cannabis in the future.

“It’s not common practice for providers to discuss cannabis use with patients who are pregnant or trying to conceive,” said the study’s corresponding author, Jamie Lo, MD, MCR, associate professor of obstetrics and gynaecology (maternal-foetal medicine) at OHSU. “I hope our work can help open up a broader dialogue about the risks of cannabis use in the preconception and prenatal period, so we can improve children’s health in the long run.”

Source: Oregon Health & Science University

One in Five Women Conceive Naturally after IVF Treatment

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Around 20% of women who needed fertility treatment, such as IVF, to conceive their first child are likely to get pregnant naturally in the future, finds a new study published in Human Reproduction. University College London researchers analysed data from 11 studies of over 5000 women around the world between 1980 and 2021, to evaluate how common it is to get pregnant naturally after delivering a baby conceived by fertility treatment.

They found that at least one in five women conceived naturally after having had a baby using fertility treatment such as IVF mostly within three years. This figure remained unchanged, even when taking into account the different types and outcome of fertility treatment – alongside length of follow up.

Infertility is defined by the failure to achieve a pregnancy after 12 months or more of regular unprotected sexual intercourse, and it is estimated to affect one in seven heterosexual couples.

However, not all women seeking and undergoing fertility treatment are absolutely or permanently infertile. And half of couples who struggle to conceive naturally in the first year of trying will go on to do so in the second year.

Not so rare an occurrence

Although it is typically considered ‘rare’ for a woman to get pregnant naturally, if she has previously had fertility treatment, the researchers want to highlight how it is not in fact an unusual event.

The team consider the findings to be particularly important, as many women may not realise that they could conceive naturally following fertility treatment. This could lead to them becoming pregnant again quickly or when they aren’t ready – which could be problematic for both the health of the mother and child.

Lead author, Dr Annette Thwaites (UCL EGA Institute for Women’s Health) said: “Our findings suggest that natural pregnancy after having a baby by IVF is far from rare. This is in contrast with widely held views – by women and health professionals – and those commonly expressed in the media, that it is a highly unlikely event.”

Much has changed since the early days of IVF and it is now used for a wide range of causes of infertility, including cases where no cause is ever found.

In addition, some women may not have experienced infertility at all but used treatment for other reasons. This could include single women using donor sperm, women in same sex relationships, surrogates or those seeking to screen for serious genetic conditions.

So, it is important for those who have had successful IVF to know how likely they are to conceive naturally afterwards.

IVF was first used in 1978 and now, more than 10 million babies worldwide have been born using the treatment – equating to between 1% and 6% of all babies born per year in the developed world by 2020.

In order to track the data more accurately and analyse which factors make natural pregnancy after having a baby by fertility treatment more likely, the researchers are calling for linked national data sets.

They hope that this information could then be used to counsel people considering their options after successful fertility treatment.

Dr Thwaites said: “Knowing what is possible would empower women to plan their families and make informed choices regarding further fertility treatment and/or contraception.”

Study limitations

Some limitations were the included studies being mostly of moderate quality with wide variation in geography, cause of subfertility, type and outcome of fertility treatment and length of follow up making direct comparisons difficult.

Source: University College London