What’s the skinny on GLP-1s and pregnancy?

Periconceptional GLP-1 receptor agonist exposure and obstetric outcomes: a Danish nationwide cohort study

Human Reproduction Open, Volume 2026, Issue 2, 2026

Pregnancy outcomes in the GLP-1 baby boom

GLP-1 receptor agonists have gone from an endocrinology niche to a reproductive-age phenomenon at remarkable speed. The problem? Ozempic babies are arriving faster than the evidence base.

The paper

Hviid et al. tackled one of the fastest-growing counselling dilemmas in reproductive medicine using Danish national registry data, examining 756,636 singleton pregnancies, including 529 with periconceptional liraglutide or semaglutide exposure. Exposure was defined as prescription redemption within 8 weeks before or after the last menstrual period.

The results

On crude analysis the outlook seems grim… GLP-1 exposure appeared associated with higher rates of pre-eclampsia, gestational diabetes, preterm birth and LGA infants.

However, the authors then performed propensity score matching. Propensity score matching is epidemiology’s version of comparing apples with apples instead of apples with watermelons, by approximating a ‘statistical twin’ for each exposed woman, helping separate the effect of the drug from the characteristics of the women taking it. In this study, this made the women exposed to GLP-1’s look as close as possible to unexposed women in terms of age, BMI, smoking, education, parity and diabetes status.

After propensity score matching, nearly all of these associations disappeared. The only outcome that remained significantly increased was preterm birth:

• Liraglutide: aOR 1.38 (95% CI 1.01-1.90)
• Semaglutide: aOR 1.51 (95% CI 1.06-2.14)

The most clinically important finding emerged when the authors stratified by indication.

Among women using GLP-1 receptor agonists for weight management without pre-existing diabetes, there was no evidence of increased preterm birth risk:

• Liraglutide: aOR 1.01 (95% CI 0.58-1.76)
• Semaglutide: aOR 0.71 (95% CI 0.30-1.70)

In contrast, women using GLP-1 receptor agonists for diabetes treatment demonstrated an increased risk:

• Liraglutide: aOR 1.70 (95% CI 1.17-2.48)
• Semaglutide: aOR 1.84 (95% CI 1.24-2.71)

The accompanying commentary makes the key point elegantly: this may represent a case of ‘when drugs meet disease’ rather than evidence of direct drug toxicity. Diabetes is already a well-established risk factor for preterm birth, and the study was unable to fully account for factors such as diabetes duration, glycaemic control or disease severity.

A particularly clever feature of the study was a ‘what if?’ analysis. What if the women taking semaglutide or liraglutide had never lost weight at all? Recognising that GLP-1 users may already have lost weight before conception, the authors modelled scenarios in which exposed women were 5–15% heavier. The results barely changed. In other words, the findings could not simply be explained away by successful weight loss.

This is still observational evidence. Prescription redemption does not confirm medication use, residual confounding remains possible, congenital anomalies were not assessed and exposed numbers were relatively modest. Nevertheless, semaglutide has become so common in reproductive-age women that ‘I got pregnant on Ozempic’ is rapidly becoming its own counselling category – and this study provides some of the most clinically relevant evidence currently available.

The Short Cycle take

This is one of the most clinically useful GLP-1 pregnancy studies published to date. The finding of increased preterm birth with semaglutide and liraglutide initially sounds alarming.

But the circumstances matter. Once obesity, diabetes and other measured confounders were accounted for as far as possible, the excess risk appeared confined to women with pre-existing diabetes rather than those using GLP-1 receptor agonists for weight loss alone.

That does not make GLP-1 receptor agonists ‘safe in pregnancy’, and current the recommendations to cease treatment before conception remain appropriate. However, these findings suggest that some of the feared complications may reflect the underlying metabolic disease rather than the medication itself.

It takes two to tango

More equitable preconception health: paternal life course opportunities for better pregnancy, child and family outcomes

Lancet 2026 April 11

Are we ignoring half of preconception care?

For years, preconception health has focused almost entirely on women: folate intake, weight, smoking, alcohol and mental health optimisation before pregnancy. Meanwhile, men have largely been reduced to a semen analysis and a reminder not to smoke too much before IVF.

This Lancet review asks an uncomfortable question – have we been overlooking half the equation?

The paper

Huang and colleagues in Lancet present a broad narrative review examining how paternal health – across the entire life course – may influence fertility, pregnancy outcomes, child development and even intergenerational health. Importantly, this is not just another sperm DNA fragmentation paper.

The authors integrate:

• Sperm epigenetics
• Paternal mental health
• Adverse childhood experiences
• Partner support during pregnancy
• Social determinants of health
• Parenting behaviours and structural inequity.

Key findings

The review summarises growing evidence that paternal obesity, smoking, alcohol use, stress, trauma and mental illness may influence offspring health through epigenetic mechanisms.

But the more clinically relevant message may actually be behavioural. Greater paternal involvement was associated with improved antenatal care attendance, lower maternal smoking and alcohol use, reduced perinatal anxiety and depression and increased breastfeeding rates.

The review also highlights links between paternal depression, adverse childhood experiences and poorer offspring mental health outcomes across generations.

The Short Cycle take

The authors argue that modern preconception care unintentionally places responsibility for pregnancy outcomes almost entirely onto women. They suggest this is not only biologically incomplete, but socially problematic.

Their proposed solution is ambitious: stop thinking about paternal preconception care as ‘three months of antioxidants before IVF’, and instead consider the lifelong health and wellbeing of boys and young men as part of reproductive medicine itself.

Nobody is changing clinic protocols tomorrow because of this review. That doesn’t mean it’s unimportant. It challenges us to think beyond sperm parameters and consider:

• Should men routinely receive formal preconception counselling?
• Are we missing opportunities to improve outcomes through paternal mental health?
• Have we over-medicalised maternal responsibility while under-recognising paternal influence?

Not every claim here is backed by causal evidence, and much of the epigenetic literature is associative. But the overall message is persuasive. Reproductive medicine has always involved two patients. Our preconception care perhaps should, too.

A fluid situation

The impact of endometrial fluid on single euploid frozen embryo transfers, to cancel or not?

Human Reproduction, Volume 41, Issue 3, March 2026

Should we cancel a euploid transfer because of endometrial fluid?

Endometrial fluid during a frozen embryo transfer cycle creates exactly the kind of clinical dilemma fertility specialists love to hate – cancel the transfer and add cost, delay and distress or proceed and risk compromising a precious embryo transfer.

The paper

Patel et al. examined this question in a large single-centre retrospective cohort of 4,308 first single euploid FET cycles performed between 2014 and 2022. Cycles were grouped into those with no endometrial fluid, fluid that resolved before progesterone start or trigger, and fluid that persisted at the decision point for transfer preparation. Importantly, patients with known hydrosalpinges were excluded, helping separate this from the classic ‘toxic tubal fluid’ scenario.

The numbers

The findings were clinically striking. Live birth occurred in 58.5% of cycles with no fluid, 49.1% where fluid resolved, and 38.3% where fluid persisted. After adjustment for age, BMI, gravidity, parity, infertility diagnosis, insemination method, FET protocol, medications, endometrial thickness and embryo grade, persistent fluid remained independently associated with significantly lower odds of live birth (aOR 0.50, 95% CI 0.30–0.85).

Even cycles where fluid resolved before transfer still trended towards poorer outcomes (aOR for live birth 0.71, 95% CI 0.47 – 1.05) than those without fluid, raising the possibility that endometrial fluid may sometimes reflect underlying endometrial dysfunction rather than simply acting as a mechanical barrier to implantation.

But should you actually cancel?

This is where the paper becomes particularly interesting. Among the 90 cycles cancelled specifically because of endometrial fluid, 58 later proceeded to a subsequent euploid FET. Live birth occurred in 39.7% – essentially identical to the 38.3% seen when transfer proceeded despite persistent fluid.

Persistent fluid appears to be a poor prognostic marker, but cancelling the cycle may not reverse that prognosis.

Notably, cancelled cycles had thinner endometrial linings on average (6.2 mm vs 8.5 mm), suggesting clinicians may already have been selectively cancelling particularly suboptimal cycles.

A small subgroup also underwent repeat ultrasound assessment after progesterone commencement despite persistent fluid. Of the 14 cycles in which fluid persisted on repeat scan, live birth occurred in only 28.6%, reinforcing the idea that persistent cavity fluid may reflect a broader issue with endometrial receptivity rather than a simple mechanical obstacle.

The Short Cycle take

Clinically, transient fluid that resolves before progesterone or trigger is probably not a reason for automatic cancellation. Persistent fluid, however, should prompt careful counselling. Live birth odds appear lower, but cancellation may simply defer the same underlying endometrial problem into another cycle. Reassuringly though, even with persistent fluid, more than one-third of transfers still resulted in live birth.

Blast from the past

Why do we remove hydrosalpinges before IVF?

By the late 1990s, concern was mounting that hydrosalpinges were more than just a marker of tubal disease – they appeared to actively impair IVF success.

The studies

Two influential meta-analyses published in 1998 and 1999 pooled largely observational IVF studies and consistently demonstrated lower implantation and pregnancy rates, and higher miscarriage rates, in women with hydrosalpinges compared with other tubal infertility patients.

The pivotal shift came with the Scandinavian multicentre randomised controlled trial by Annika Strandell and colleagues in 1999. The trial randomised 186 women with ultrasound-visible hydrosalpinges to salpingectomy before IVF or no surgical intervention. Delivery rates were 28.6% after salpingectomy versus 16.3% with expectant management – a roughly 75% relative increase. In women with bilateral hydrosalpinges, the benefit was even greater (40.0% vs 17.5%) – a doubling of birth rates.

The study provided the first prospective evidence that treating the hydrosalpinx itself, rather than simply accepting it as a marker of severe tubal disease, could meaningfully improve IVF outcomes.

What still holds up?

Surprisingly, quite a lot. More than two decades later, the evidence base still rests on relatively few randomised trials, many small and examining alternative interventions such as proximal tubal occlusion rather than salpingectomy alone.

Yet the overall signal has remained remarkably consistent.

The Short Cycle take

This is a good example of how reproductive medicine often evolves – strong biologic plausibility and accumulating observational evidence driving practice change, with a remarkable amount of modern practice tracing back to a surprisingly small number of randomised trials.

Worth a mention

10,000 steps to implantation?

Patients still frequently ask whether they should ‘take it easy’ after embryo transfer. In the SSTEP trial, a prospective cohort study of 82 programmed FET cycles in Fertility and Sterility, wearable Fitbit data showed no difference in step counts, activity levels, heart rate, sleep or cortisol-measured stress between those who conceived and those who did not. Interestingly, patients who conceived actually showed a small increase in activity after transfer, while those who did not tended to reduce their steps. The study was not powered to prove benefit from activity, but it is reassuring evidence that routine movement (and probably normal life) does not appear harmful after FET.

Selecting for the future

In 2022, Nature Medicine launched the modern Preimplantation Genetic Testing for Polygenic Disorders (PGT-P) era – the kind of paper that once belonged firmly in science fiction. The concept is striking; using embryo DNA to estimate future risk of conditions such as coronary artery disease, diabetes, and some cancers, then selecting embryos accordingly.

PGT-P is not currently part of Australian practice, but could be one day. A recent Fertility and Sterility commentary, ‘Don’t let hype outrun evidence’, explores the tension between innovation and caution – modest absolute risk reductions, uncertain clinical utility, ancestry bias, commercialisation and the uncomfortable proximity to ‘designer babies’.

Final fun fact – unexpected fertility advantage unlocked

A Danish study of nearly 90,000 pregnant women found that atopic dermatitis was associated with faster conception and less use of fertility treatment. The authors speculate that a pregnancy-friendly TH2 immune bias may be part of the reason. Maybe eczema belongs on the dating profile after all.

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