What is the short and long-term impact of ART on the physical and psychological health of patients, newborns, and children? This was the fundamental question this two-day campus attempted to answer with an extensive evaluation of evidence relating to every step of the ART journey and beyond.
The workshop in Naples was organised by SIGs Implantation and Early Pregnancy and Safety and Quality in ART, and over 26 countries were represented among the attendees. A total of six sessions took place showcasing the latest research on clinical protocols in IVF; third-party reproduction; ART interventions; embryo culture; confounding factors such as nutrition and an infertility diagnosis; and genetics, psychology and ethics.
The overriding message was a positive one: improved practices such as single embryo transfer (SET) have helped to decrease risks. However, better quality and ongoing research is needed to offer patients both safety and the hope of a successful outcome.
A keynote lecture by Anja Pinborg, from the University of Copenhagen, focused on the health of children conceived by ART. Her presentation explored whether the increased risks are associated with the fertility treatment itself or with maternal or paternal factors related to subfertility such as endometriosis, PCOS, genetics and age.
The likelihood of preterm birth and cerebral palsy has diminished significantly over time which means children born after ART can now expect similar health to that of the general population. However, the evidence suggests a higher chance of puberty disorders, and semen quality in boys conceived after ICSI is lower compared to those conceived naturally. No link has been established between ART and increased type 2 diabetes but there is an association between ART and increased obesity. As such, cardiometabolic health should be investigated further in longitudinal studies said Professor Pinborg.
The pros and cons of frozen embryo transfer (FET) vs fresh was a recurring debate throughout this campus. Data presented by Professor Pinborg suggests risk of hypertensive disorders such as preeclampsia is elevated three-fold in FET, and is highest following artificial FET cycles which preclude the development of a corpus luteum. The more pregnancies that can be made with the corpus luteum, the better, she said, because of the gland’s crucial role in preparing the body for pregnancy and childbirth. This shift towards natural cycle IVF and lower risk ART was another theme repeated during the workshop. Professor Pinborg also discussed data on cancer incidence and ART which she said was reassuring in general. However, FET is associated with increased odds of childhood cancer particularly leukaemia although the message for cancer incidence for ART in general is reassuring, she said.
In summing up, Professor Pinborg said there is ‘a huge obligation’ to follow the health of the more than 10 million children who have been born to date with the assistance of fertility procedures and treatments. To protect them, Professor Pinborg said SET should be standard care, natural or modified natural cycle FET should be used whenever possible, and freeze-all should only be used by indication such as to minimise the risk of ovarian hyperstimulation syndrome (1).
The contribution of maternal and paternal issues was explored in more depth by Professor Pinborg in a separate session on confounding factors. When maternal factors are controlled for, the evidence suggests the influence of ART procedures diminishes. The challenge facing research, said Professor Pinborg, was how to disentangle their role from that of ART when establishing risk. To control for comorbidity such as diabetes and congenital heart disease is crucial otherwise infertility will bias ART pregnancy follow-up. Her conclusion was that studies need to be designed correctly including sibling analyses which otherwise can be biased by carryover effects.
The session on the impact of third-party reproduction looked at gestational, perinatal and postnatal outcomes in donor oocyte and sperm cycles, and in surrogacy. Demand for third-party reproduction is constant, a trend which is set to grow especially with the advent of ICSI. As such, there is a strong need to study safety issues both in the short and long-term from a health perspective, and to determine any psychological impact of such approaches.
Egg donation was the first third-party technique discussed. Alberto Vaiarelli said egg donor programmes need to consider the link between higher risk and women not only of advanced maternal but also of uterine age. A higher incidence of pregnancy-induced hypertension is related to immunologic changes being more pronounced in egg donor pregnancies. On this basis, more extensive research into women’s immunological response could help optimise protocols and improve success rates said Dr Vaiarelli from Genera Roma. Egg donor (and sperm) selection can be personalised based on the recipient’s or embryo’s immune profile using KIR/HLA genotyping or matching but there is no data to demonstrate benefit.
As for donor sperm treatments, there is little evidence available on the effects according to a presentation by Nicola Marconi from the University of Aberdeen. Sperm donation has been linked with increased miscarriage and ectopic pregnancy risk but data are of very low quality and often contradictory. Dr Marconi said hypertensive disorders in pregnancy are the only health issue reported consistently and are likely associated with increased risk of ART. Uncertainty exists around other outcomes such as birth weight and data on obstetric outcomes is sparse hence continuous monitoring of patients is needed.
With surrogacy, the woman who carries the unborn child takes all the risks and the arrangement is banned in many European countries. A recent ESHRE ethics committee report concluded that, while non-commercial surrogacy is acceptable, commercial arrangements are likely to result in exploitation (2). A systematic review presented and co-authored by Professor Christina Bergh, from the University of Gothenburg, suggests there are no substantial adverse medical psychological problems for women who are gestational carriers or for the children they give birth to (3). However, much of the data had methodological limitations and few follow-up studies exist.
PGT was among topics discussed in the session on ART interventions. An invasive procedure, PGT is not standardised in labs although trophectoderm biopsy is currently the most used approach with reassuring data on short-term outcomes as presented by Alessandra Alteri, co-ordinator of SIG Safety and Quality in ART. No significant increased risk for most obstetric, neonatal or childhood outcomes is documented, especially when compared to IVF/ICSI. However, data are limited on the long-term effects of biopsies on the health of children. Overall, Dr Alteri said evidence is weak or heterogeneous – she said results must be interpreted cautiously due to confounding factors such as infertility or embryo freezing. Although it appears there is no significantly increased risk if PGT is done under optimal conditions, more randomised controlled trials are needed to further confirm the safety of biopsies.
In an interview with Focus on Reproduction during the campus, Dr Alteri said the key information to take away included that clinics should maximise the chances of IVF without compromising children’s health and safety. The aim of ART, she said, should not solely focus on quantity (of eggs retrieved) but also on competence and quality. This will help protect current and future generations.
References:
1 Pinborg A, Blockeel C, Coticchio G, Garcia-Velasco J, Santulli P, and Campbell A. Speaking up for the safety of the children following frozen embryo transfer. Hum Reprod Open 2024; Vol 2024 (4); https://doi.org/10.1093/hropen/hoae058
2 Writing Group on behalf of the ESHRE Ethics Committee, Francoise Shenfield, Basil Tarlatzis, Guiliana Baccino, Theofano Bounartzi, Lucy Frith, Guido Pennings, Veerle Provoost, Nathalie Vermeulen, Heidi Mertes, Ethical considerations on surrogacy. Hum Reprod March 2025; Vol 40 (3); 420–425; https://doi.org/10.1093/humrep/deaf006
3 Söderström-Anttila V, Wennerholm U-B, Loft A, Pinborg A, Aittomäki K, Bente Romundstad L, Bergh C. Surrogacy: outcomes for surrogate mothers, children and the resulting families—a systematic review. Hum Reprod Update; Vol 22 (2) 2016; 260 –276; https://doi.org/10.1093/humupd/dmv046
You have to be logged in and an ESHRE member in order to comment.