Fertility
Study reveals how assisted reproduction affects placenta and child’s growth
Approximately one in six couples trying to have a child experiences infertility. Each year, over five percent of children in Finland are born with the help of Assisted Reproductive Technology (ART), and to date, over ten million children worldwide have been conceived using these techniques.
Although ART-conceived children are generally healthy, a slightly increased risk of growth disturbances as well as cardiovascular, metabolic, and neurodevelopmental disorders has been observed. The underlying causes of the risks, and whether they result from the ART procedures or parental subfertility, are unknown.
To understand the molecular mechanisms behind ART-associated risks, researchers have examined newborns and placentas from 80 ART and 77 spontaneous pregnancies. When the placentas were compared, they considered different ART methods as well as the children´s sex for the first time.
The placenta has proven to be an extremely fascinating organ which connects the mother and the foetus, mediates environmental effects on the foetus and influences foetal development.
“The placenta offers a unique window into the very early developmental stages, which are otherwise difficult to study in human”, says associate professor Nina Kaminen-Ahola, the leader of the study in the University of Helsinki.
Frozen embryo transfer resembles natural pregnancy
Genome-wide placental gene function and DNA methylation, the most well-known epigenetic mark involved in gene regulation, were examined. Also, potential connections between the observed changes and the placental weight as well as newborns’ weight and height were studied.
One of the most interesting findings concerned the two commonly used ART methods, fresh and frozen embryo transfer. In the fresh embryo transfer, the IVF-fertilised embryo is transferred directly from the culture dish into the uterus, while in the frozen embryo transfer the embryo is frozen for a varying period before the transfer.
Several studies have discovered that placentas and children from fresh embryo transfer are smaller on average compared to those from frozen embryo transfer. This was also the case in the current study. Particularly, it was seen that the observed changes related to metabolism and growth were specific only to placentas from fresh embryo transfers.
“Almost all placentas from frozen embryo transfers had been transferred into the uterus during the mother’s natural cycle, rather than during an artificial hormone surge as in the case with fresh embryo transfers. Consequently, the onset of pregnancy in these cases resemble more spontaneous pregnancies,” explains Pauliina Auvinen, the doctoral researcher on the project.
Altered gene is linked to obesity and diabetes
In addition, the researchers identified altered function of a gene called DLK1. The expression of this gene was reduced in both ART placentas and in placentas from pregnancies of subfertile couples who had applied for fertilization treatment but who got pregnant spontaneously.
The DLK1 gene regulates metabolism and has been associated previously with obesity and type 2 diabetes. Additionally, it can have a role in maternal physiological adaptations to pregnancy.
According to a previous mouse study, Dlk1 is essential for proper maternal fasting response during pregnancy, enabling the switch to using fat for energy resource and thereby securing foetal growth. Silencing of Dlk1 was also associated with the offspring’s lower birth weight.
Kaminen-Ahola says that the silencing of DLK1 gene has also been linked to low birth weight in humans.
“The role of this gene in subfertility and the increasing metabolic disorders such as obesity and type 2 diabetes,” needs to be further clarified.
More research needed
Despite the significant new results, more samples need to be collected to better understand the effects of the different fertility treatment methods, subfertility, and sex on the children´s development and health. In addition, understanding the long-term impact of ART requires long-term monitoring of the children.
“Based on the results, it will be possible to improve ART treatments and understand the causes of sub- and infertility. We are continuously collecting more samples, and we warmly thank all the families for participating in the epiART study,” said Kaminen-Ahola.
Onto Health has acquired Levy Health, a fertility software company providing precision diagnostics and patient intake for reproductive medicine.
The acquisition, fuelled by Onto Health’s US$20m Series A fundraise in April, supports its plan to build scalable, tech-enabled infrastructure for reproductive medicine.
Onto founder Roohi Jeelani, MD, called it the first of several moves in the company’s expansion strategy in a LinkedIn post, adding that there was “more coming soon”.
She said: “This isn’t just an acquisition, it’s proof of how we’re building Onto: physician-led, tech-enabled, and built to scale without losing the personal touch fertility patients deserve.”
Headquartered in Chicago, Onto Health combines evidence-based fertility care with artificial intelligence-driven diagnostics, clinical automation and longevity science.
AI-driven diagnostics use software to analyse patient information and support clinical decision-making, rather than replace clinicians.
Levy Health, founded in Berlin with US offices in San Francisco, helps medical providers identify endocrine disorders more quickly and helps clinics streamline fertility workups.
Endocrine disorders affect the body’s hormone system, which can influence ovulation, menstrual cycles and fertility.
Co-founder Caroline Mitterdorfer said joining Onto would expand Levy Health’s fertility care tools to more clinics and patients, helping physicians focus on patient care.
Onto opened its first clinic in Chicago in February, with plans for three more in the greater Chicago area.
The company said in April that it would use its new funding, led by Artis and Humania, to support additional operations in the US and expand into the Gulf Cooperation Council.
The Gulf Cooperation Council includes six Arab states bordering the Persian Gulf.
Softening ageing ovaries could help women remain fertile for longer, early animal research suggests.
Fertility declines with age for several reasons, including poorer egg quality, fewer ovarian follicles and the gradual stiffening of ovarian tissue.
Existing fertility treatments, including hormone therapy and in vitro fertilisation, mainly address hormonal imbalances or help eggs mature or become fertilised.
Scientists are now examining whether changing the physical structure of the ovaries could provide another route for future fertility treatments.
Stuart A. Cook, of the Cardiovascular and Metabolic Disorders Programme at Duke-National University of Singapore Medical School, published an accompanying commentary on the research.
Researchers led by Shixuan Wang at Huazhong University of Science and Technology in Wuhan, China, collected healthy ovarian tissue from younger, middle-aged and older women.
They also examined samples from patients with polycystic ovary syndrome, known as PCOS, premature ovarian insufficiency, or POI, and endometriosis.
PCOS is a hormonal condition that can disrupt ovulation. POI occurs when the ovaries stop working normally before the age of 40, while endometriosis causes tissue similar to the womb lining to grow elsewhere in the body.
Tests of protein levels and gene activity found higher levels of the inflammatory protein interleukin-11, or IL-11, in ageing and diseased ovaries.
In laboratory experiments, the researchers exposed ovarian fibroblasts to IL-11. Fibroblasts are cells that produce connective tissue.
The protein caused the cells to produce excess collagen, a structural material that can build up during scarring and make tissue stiffer.
The researchers then genetically modified mice so they could not respond to IL-11. The animals developed less ovarian stiffening and maintained better ovarian function as they aged.
Similar results were seen in mouse models of PCOS and POI caused by chemotherapy.
In the final part of the experiment, older mice and rats were injected with a nanoparticle treatment containing small interfering RNA, or siRNA, designed to switch off IL-11.
The treatment made the animals’ ovaries less stiff and improved fertility.
Pregnancy rates among older mice rose from 25 per cent to 50 per cent, while average litter sizes also increased.
More rats treated with the therapy became pregnant and produced larger litters.
The approach remains highly speculative and will require considerably more research before its safety or effectiveness in women can be established.
However, the researchers said blocking the inflammatory pathway could eventually form the basis of new fertility treatments.
They said: “We propose that anti-IL-11 therapy represents a promising translational strategy for delaying ovarian ageing.”
W Group has opened applications for W Accelerate with Merck KGaA and M Ventures, inviting reproductive and maternal health startups, scaleups and spinouts to pitch for direct access to global pharma partnership and strategic investment.
Selected companies will pitch on 5th October, competing for the chance to accelerate their growth through commercial partnerships, investment, or both.
This is the third time Merck KGaA, a global leader in reproductive health, has partnered with W Group on the programme, which exists to close the innovation and investment gap in women’s health by connecting the sector’s most promising startups directly with the corporates and investors positioned to scale them.
What Merck KGaA and M Ventures are looking for
This year’s call is focused on breakthrough solutions in female infertility, fertility preservation, adenomyosis, endometriosis, polyendocrine metabolic ovarian syndrome (PMOS), ovarian insufficiency, preeclampsia and pregnancy comorbidities.
New for this round, applicants choose between three pathways depending on what they need from the programme:
- The Partnership Lane, for companies seeking commercial collaborations and strategic relationships
- The Investment Lane, for founders looking to connect with investors and secure funding to scale
- The Dual Lane, for innovators pursuing both partnership and investment opportunities
How the Accelerate event works
Selected companies get a 1:1 pitch practice session ahead of time, then a private 30-minute session with Merck KGaA and M Ventures leadership on the day itself, small-group sessions with regulatory and investment strategy experts, an “Ask Merck Anything” roundtable, and a VIP networking reception.
Key dates
- Open call launches: 8th July
- Open call closes: 2nd September
- Notification of successful companies: 11th September
- Pitch day: 5th October
Applications are open now at wplatform.typeform.com/to/KGzviBQM.
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