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Older women face lower chance of fertility treatment working, even with donor eggs, study finds

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IVF success declines with age even when women use young donor eggs, with a marked fall from around 49, research suggests.

The findings challenge the idea that donor eggs can fully “reset” the reproductive clock, although researchers said they should not discourage older couples from trying.

Dr Beatrice Crestani, from an assisted reproduction medical institute in Italy, said reproductive ageing had traditionally been seen mainly as an issue involving the ovaries.

She said replacing older eggs with younger donor eggs was often believed to “reset” the reproductive clock.

Dr Crestani added: “Our findings suggest the picture is more complex.”

The study followed 1,774 women undergoing in vitro fertilisation, or IVF, using donated eggs. IVF involves fertilising an egg in a laboratory before transferring an embryo to the womb.

Women in their mid to late 30s had a 54 per cent chance of becoming pregnant after treatment, compared with around 43 per cent among those aged 49 or older.

Live birth rates fell from 46 per cent to 32 per cent, while miscarriage rates rose from 24 per cent to 38 per cent.

Women aged 49 and older had twice the risk of miscarriage compared with those aged 35 to 40.

Researchers believe changes to the endometrium with age may help explain the difference. The endometrium is the lining of the womb where a fertilised egg or embryo implants and grows.

Although the thickness of the womb lining was similar across the age groups, its condition declined with age.

Researchers said future work might find ways to predict, prevent or improve uterine ageing.

Dr Crestani said: “These findings should not discourage women from pursuing donor-egg treatment, because success rates remain meaningful even at advanced ages.

“However, patients should be counselled that donor eggs cannot completely eliminate the effects of reproductive ageing, particularly beyond 49 years.”

Among women who transferred all their available embryos, the live birth rate was around 80 per cent for those aged 35 to 40 and 62.5 per cent for those aged 49 or older.

Experts stressed that the health of the womb and ovaries differs between women.

There is no legal upper age limit for IVF in the UK, unlike some European countries. Greece has an upper limit of 54.

Women in the UK can donate or share their eggs up to the age of 36.

Regulators ask private UK clinics to assess the welfare of any resulting child and whether the recipient can safely carry a pregnancy.

NHS guidelines recommend offering three IVF cycles to women up to the age of 40 and one cycle to women up to the age of 42.

Patients using donor eggs usually have to fund that part of the treatment themselves.

People conceived using sperm, eggs or embryos from donors registered after 1 April 2005 can request identifying information about their biological donor parent once they turn 18.

The findings are being presented at the European Society of Human Reproduction and Embryology.

Professor Borut Kovacic, chair-elect of the society, said researchers were trying to better understand the “cross-talk” between an implanting embryo and the womb lining. This refers to the biological signals exchanged during implantation.

He said the age threshold associated with the beginning of a loss of uterine function was unlikely to be absolute.

Professor Kovacic added: “It provides important information for patients and offers a valuable foundation for future research aimed at identifying novel biomarkers of uterine ageing.”

Dr Ippokratis Sarris, chair-elect of the British Fertility Society, called for more research.

He said pregnancies could carry greater risks for older women and recommended thorough health checks and counselling for couples beginning fertility treatment.

Fertility

Chelsea FC Women to launch first-of-its-kind player fertility fund

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Chelsea FC Women is to launch a fertility fund giving players access to assessments, treatments, counselling and workshops.

The initiative is part of a new partnership with London fertility clinic Fertility Plus, which has been named the club’s official fertility partner.

Chelsea said the fund will be available to every player in its women’s team, with support tailored to individual needs.

Giulia Mazzia, commercial director for Chelsea FC Women, said: “At Chelsea FC Women we are never done pushing for progress for our players and our community.

“This first-of-its-kind partnership with Fertility Plus will open up the conversation about fertility, help to raise awareness for our incredible fanbase and beyond, and give practical support to our players off the field as well as on it.”

Support through Fertility Plus will include fertility assessments and treatments, as well as counselling and workshops.

The partnership will also provide evidence-based information about reproductive health and address misconceptions around fertility.

Chelsea cited previous research on fertility knowledge which found that 41 per cent of respondents actively trying to conceive did not know when their fertile window was.

The club and Fertility Plus plan to provide educational content, resources comparing fertility myths with medical evidence and insights from Chelsea FC Women ambassadors.

Dr Amit Shah and Dr Anil Gudi, co-founders of Fertility Plus, said: “Elite sport asks a lot of women during the very years when fertility matters most, yet it’s a conversation the game has rarely had.

“Partnering with Chelsea FC Women allows us to help change that by giving players, staff and supporters access to trusted fertility expertise and compassionate, consultant-led care.

“We’re proud to work alongside a club that’s setting a new standard for supporting women’s health, both on and off the pitch.

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Higher doses of common fertility drug may increase pregnancy risks

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Higher cumulative doses of common fertility drug clomiphene citrate may increase pregnancy loss risks, according to new research.

Around one in six people experience infertility, with irregular or absent ovulation among the most common causes.

Clomiphene citrate has long been a mainstay of fertility treatment, but Adelaide University research has raised concerns about higher cumulative doses.

The new study found that high doses of clomiphene citrate accumulated over multiple fertility treatment cycles could increase the risk of pregnancy loss.

Lead author associate professor Sheree Boulet said the findings showed a clear dose-response relationship, meaning the risks increased as cumulative exposure rose.

She said: “Women who received higher cumulative doses of clomiphene citrate experienced progressively greater risks of adverse pregnancy outcomes.

“We examined more than 21,000 embryo transfer cycles across four cumulative dose categories and found that increasing the dose did not significantly improve the chance of a live birth.

“Our findings suggest there may be a point where increasing the dose offers little additional benefit while exposing women to greater risk, highlighting the importance of carefully balancing effectiveness with safety when making treatment decisions.”

Supported by the NHMRC and conducted in partnership with Boston University and the Centers for Disease Control and Prevention, researchers analysed 21,004 IVF embryo transfer cycles in the US.

Women receiving cumulative doses of 500mg to 749mg of clomiphene citrate had a 12 per cent higher risk of miscarriage, while those receiving 750mg to 999mg had a 38 per cent higher risk.

Women receiving cumulative doses of 750mg or more were also more than twice as likely to have twins or other multiple births.

Rates of spontaneous abortion, another term for miscarriage, increased as the dose rose.

Researchers also recorded more than a threefold increase in stillbirth at the highest dose, although the finding was not statistically significant because that dose was rare. Larger studies are needed to confirm the association.

The finding is consistent with an earlier Adelaide University study that showed a doubling of neonatal death in pregnancies involving clomiphene citrate. Neonatal death means the death of a baby shortly after birth.

Higher cumulative doses did not improve the chance of a live birth, but did increase twinning, which raises the risk of adverse outcomes for both mother and child.

Clomiphene citrate is one of the world’s most widely prescribed fertility drugs. It has been prescribed to millions of women worldwide since 1967 and remains a recommended first-line treatment for ovulation induction.

The drug is recognised as an essential medicine by the World Health Organization. It works by stimulating the ovaries to release eggs, increasing the chance of pregnancy.

Women who do not respond to lower doses, or who require multiple treatment cycles, may receive progressively higher cumulative doses over time.

The findings build on a series of studies from Adelaide University’s Robinson Research Institute linking clomiphene citrate with increased risks of pregnancy loss, stillbirth, perinatal death and some birth defects.

Experimental studies in mice supported these findings, showing that higher doses reduced successful pregnancies and were associated with pregnancy loss, impaired fetal growth and developmental abnormalities.

Professor Michael Davies, senior researcher and co-author of all the studies, said the latest work builds on more than two decades of Adelaide-led research into the safety of fertility treatments.

He said: “Clomiphene citrate has been used by many women since 1967, but it has never been comprehensively evaluated in large prospective clinical trials.

“Our studies indicate that women respond differently to clomiphene citrate and that increasing cumulative doses may increase the risk of adverse pregnancy outcomes without improving the likelihood of a live birth.

“The findings confirm and extend our previous studies in both human and mouse models which highlight the need to better understand the dose-response relationship and whether more personalised dosing strategies could improve safety.

“Until we can better understand these differences, it remains important that clinicians rigorously follow manufacturer’s safety recommendations and avoid unnecessarily increasing cumulative doses.

“The same questions are now being asked of newer ovulation-inducing medications, so any move away from clomiphene citrate should also be guided by robust evidence rather than assumptions about safety.”

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No clear evidence common embryo transfer techniques improve IVF success, review finds

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Common IVF preparation techniques used before embryo transfer have no proven effect on pregnancy rates, according to a review.

Researchers said evidence for the widely used practices remains uncertain because available studies are limited and generally of low quality.

Embryo transfer is the final and most vulnerable stage of IVF, when an embryo is placed into the womb. Only around one in three transfers results in pregnancy.

Practice varies between clinics, with some routinely using preparation techniques such as adjusting bladder fullness while others do not consider them necessary.

Dr Ryosuke Akino, practising obstetrician-gynaecologist from Kato Ladies Clinic, said: “To an extent, this is a case of tradition driving practice rather than the evidence.

“Current practices in this area often reflect local protocols, clinician preference, and historical convention rather than strong, high-quality evidence.”

The Cochrane review analysed 11 studies involving 2,524 women undergoing embryo transfer.

Researchers looked at three preparation techniques used by fertility clinics: having women arrive with a full bladder to straighten the angle between the uterus and cervix, removing cervical mucus and using a technique called afterloading.

Afterloading is a technique used to guide the embryo through the cervix.

The review found no reliable evidence that any of the three approaches improved pregnancy rates compared with standard care.

Researchers rated the evidence as low or very low certainty because the trials were small and had methodological weaknesses. They found no grounds to recommend any of the techniques over standard care.

There was also limited information about possible side effects.

The review team, which included methodologists and practising obstetrician-gynaecologists, said full bladder preparation and cervical mucus removal were generally considered safe, with no clear evidence of harm or major complications.

Dr James Brown, obstetrician-gynaecologist from Women’s Health and Research Institute Australia, said: “While these techniques are generally considered safe, it’s still important to test their effectiveness.”

Akino and Brown added: “A full bladder can be uncomfortable, although it may ease catheter insertion in certain uterine positions and reduce procedural difficulty.

“Mucus removal is usually quick, but if done roughly and causes bleeding, it may affect the woman’s experience.

“Overall, the risks are minor and relate mostly to discomfort and procedural factors rather than clinical harm.”

The authors said embryo transfer has changed relatively little despite major advances elsewhere in IVF.

Research has instead focused more heavily on embryo quality and genetic factors, which have a greater bearing on treatment success than transfer technique.

Embryo transfer also depends heavily on the person carrying out the procedure and can be difficult to standardise, making large, rigorous clinical trials harder to design.

Researchers said women may also be reluctant to risk valuable embryos by taking part in randomised studies comparing different transfer techniques.

Dr Noyuri Yamaji from Showa Medical University in Japan said: “Sixteen years of research still haven’t answered a basic IVF technique question.

“This is a critical step in the IVF process and these small changes and techniques have the possibility to make a massive difference, but we won’t know more until more robust, better-quality trials are conducted.”

All the studies assessed were carried out in high-income countries, meaning the findings may not necessarily apply to other healthcare settings and populations.

The authors said further research could be particularly valuable in resource-limited settings, where these procedures are inexpensive and simple to change and basic procedural standardisation could matter more than advanced technical modifications.

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