“More Boys from Frozen Embryo Transfers?”… What Tens of Thousands of IVF Cycles Reveal About the Offspring Sex Ratio
- Male Ratio of 51.9% in Frozen Blastocyst Transfers… Surging to 58.7% in an Analysis of 28,000+ Chinese Cycles
- It Wasn’t the ‘Freezing and Thawing’… 5- to 6-Day Culture and Blastocyst Selection Likely Skew the Sex Ratio
- ICSI Skews Toward Females Instead… “Not at a Level to Predict the Sex of Individual Embryos”
“Frozen embryo transfers produce more sons.”
This is a long-standing anecdotal claim shared among patients undergoing In Vitro Fertilization (IVF). As personal accounts of having boys after frozen-thawed embryo transfers (FET) accumulated, it gradually evolved into a widely accepted “rule of thumb” in fertility clinic waiting rooms and online communities.
This claim cannot be dismissed as pure myth. Epidemiological analyses tracking tens of thousands of assisted reproductive technology (ART) cycles have repeatedly confirmed a higher-than-average proportion of male births under specific protocol conditions.
However, scientific evidence points in a different direction than commonly assumed: the factor shifting the sex ratio is not the process of “cryopreservation” itself, but rather extended culture to Day 5–6 and the morphological selection of advanced blastocysts.
SART and Large-Scale Data: Blastocysts Shift the Sex Ratio Toward Males
A large-scale analysis utilizing registry data from the Society for Assisted Reproductive Technology (SART) in the United States demonstrated that among frozen embryo transfers:
- Blastocyst Transfers (Day 5–6): Resulted in 51.9% male births.
- Cleavage-Stage Transfers (Day 2–3): Resulted in 50.5% male births.
While the absolute difference was 1.4 percentage points, the association between blastocyst transfer and higher male birth rates persisted even after adjusting for maternal age, body mass index (BMI), and male-factor infertility.
A large cohort study from China revealed an even wider gap:
- Analyzing 28,376 frozen embryo transfer cycles resulting in 9,217 live births, the proportion of male offspring was 58.7% following blastocyst transfers compared to 51.6% following cleavage-stage transfers.
Even within the exact same category of frozen transfers, the sex ratio diverged substantially depending on embryonic developmental stage at the time of transfer.
The Mechanism: Extended Culture and Blastocyst Selection Bias
Embryos do not divide at identical speeds post-fertilization. Some develop rapidly, some progress slowly, and others arrest during in vitro culture. In clinical practice, embryologists prioritize Day 5 or Day 6 blastocysts displaying the highest developmental pace and morphological grades.
This laboratory selection process is hypothesized to subtly alter the secondary sex ratio:
- An analysis of over 6,300 single frozen blastocyst transfers found that higher blastocyst quality correlated with higher male birth rates.
- In particular, blastocysts with higher-grade trophectoderm (TE) morphology and faster blastocoel expansion rates yielded a significantly higher proportion of male offspring.
If male (XY) embryos divide slightly faster or achieve higher morphological scores under certain culture conditions, embryologists selecting the “best-looking, most expanded blastocyst” are statistically more likely to select a male embryo.
However, this does not mean every high-grade blastocyst is male, nor do male embryos universally outpace female embryos. Several studies have found no significant link between cleavage speed and sex. The documented effect represents a modest statistical tilt across large population cohorts, not an absolute biological rule for individual embryos.
ICSI Skews the Ratio Toward Females
Another major variable influencing the offspring sex ratio is the fertilization method.
Unlike conventional IVF, where sperm naturally fertilize an oocyte, Intracytoplasmic Sperm Injection (ICSI) involves an embryologist manually injecting a single selected sperm into an egg. Across multiple large registries, ICSI has consistently been associated with a lower proportion of male births (skewing toward females):
- In the analysis of 28,376 Chinese FET cycles:
- Conventional IVF: Resulted in 53.7% male births.
- ICSI: Dropped to 50.1% male births.
- A multicenter study across 18 Chinese fertility centers analyzing over 120,000 live births demonstrated identical trends: multivariable adjustments confirmed that blastocyst transfer independently favored male births, whereas ICSI independently shifted the ratio toward female births.
If the freezing process were the sole driver of male sex skewing, this divergent effect based on fertilization method could not occur. The sex ratio in ART reflects a complex interplay of fertilization modality, culture duration, embryo kinetics, and morphological selection criteria.
Fresh vs. Frozen Comparisons: Inconsistent Evidence
Direct comparisons between fresh and frozen embryo transfers further disprove the “freezing makes boys” hypothesis:
- Studies directly comparing fresh vs. frozen transfers show inconsistent findings; several trials demonstrate that fresh transfers yielded equal or even higher male ratios than frozen transfers.
- In an analysis of donor oocyte cycles, the male birth rate was 54.5% in fresh transfers vs. 50.9% in frozen transfers.
- Other trials have shown no statistically significant difference in sex ratio between fresh and vitrified cohorts.
If cryopreservation and thawing biologically selected for male embryos, this pattern would be consistently reproducible across all comparative studies.
Consequently, current clinical evidence is best summarized as: “Rather than frozen transfers generating more boys, extended culture to the blastocyst stage in ART introduces a modest population-level skew toward male births.”
Clinical Takeaways for Patients
With contemporary IVF protocols standardly adopting extended culture to Day 5–6 blastocysts followed by freeze-all cycles, patients frequently observe more male births among peers. However, extended culture and morphology grading are the primary drivers behind this trend, not cryopreservation.
Furthermore, population statistics ranging between 51% and 59% male births cannot be used to predict the sex of an individual embryo. These figures are derived from observational epidemiological datasets encompassing diverse clinics, culture media, and patient demographics.
For any individual patient undergoing a Day-5 frozen transfer, the biological probability for that specific embryo remains effectively close to 50/50. While the popular belief contains a grain of scientific truth, the determining factor was never the liquid nitrogen—it was how long the embryo was cultured and how it was selected in the laboratory.
※ This article was synthesized based on registry analyses from the Society for Assisted Reproductive Technology (SART) and peer-reviewed research on assisted reproductive technology and secondary sex ratios published in Human Reproduction, Scientific Reports, and Reproductive BioMedicine Online (RBMO). It does not replace individual medical diagnosis or clinical care, and specific clinical decisions must be made in consultation with a qualified specialist physician.
※ The images associated with this article were generated using generative AI (ChatGPT, OpenAI) as visual references and do not depict real individuals.