Egg-meet-sperm moments are equal opportunities for girls and boys

Girl or boy: For expecting parents, it’s a classic question. For scientists studying human demographics, it’s a head scratcher.

Statistics seem to favor boys. On average, for every 105 boys born, only 100 girls are born. Scientists have credited the difference to more male embryos being conceived. But that’s not true, a new study suggests.

Researchers from the United States and the United Kingdom analyzed data from roughly 35 million embryos, fetuses and births and conclude that at conception, the ratio of male to female embryos is roughly 50-50. The sex ratio may skew slightly in favor of females in the first week or so after conception. But then it flips to favor males starting at 10 to 14 weeks, possibly explaining why slightly more boys than girls are born. The team reports the findings online March 30 in the Proceedings of the National Academy of Sciences.

The results contradict widespread expectations about the trajectory of the human sex ratio from conception to birth, says study coauthor Steven Orzack of Fresh Pond Research Institute in Cambridge, Mass.

For hundreds of years, scientists have observed that more boys are born each year than girls. To explain the difference, scientists suggested that more males must be conceived. More male embryos and fetuses also seemed to die in pregnancies, scientists claimed.

Orzack and colleagues found just the opposite. They collected sex data from embryos conceived with assisted reproductive technology; fetuses that were aborted or had their amniotic fluid or tissue tested; and U.S. census records of births and deaths. The data suggest that males and females are conceived in roughly equal numbers and that more female than male embryos and fetuses die in utero.

Male embryos, however, do have a higher mortality rate than female embryos at one point during pregnancy: within a week or two of conception. Perhaps more male embryos develop abnormally in this early stage, causing them to die at a higher rate, the scientists suggest. Later on, from week two to 12, female mortality begins to outpace male mortality because of abnormalities in how specific genes are activated or inactivated during embryonic development, the researchers propose.

Understanding fluctuations in sex ratios as embryos are developing opens the door for studies that could ultimately help doctors find ways to stop preventable fetal deaths and improve pregnancy outcomes, says Kristen Navara, a biologist at the University of Georgia in Athens.

The team’s data from assisted reproductive technology, which can provide sex data as early as three days after conception, and from tests to monitor high-risk pregnancies fill in an important piece of the puzzle in human sex ratio trajectory, she says. However, she notes some limitations. For example, women who have tissue or fluid collected a few weeks into a pregnancy are typically at risk of having fetuses with abnormalities and that won’t survive. Their experiences may not reflect what’s happening in all pregnancies.  

“It is possible that the male-biased sex ratios found during the first and second trimesters could reflect something inherently different in this group of women rather than a natural sex ratio pattern,” Navara says.

The majority of these babies are healthy, suggesting that information from these pregnancies is as representative as any that is currently available, Orzack argues. But he and his colleagues agree that the data have some gaps. It is nearly impossible to get data from embryos that are 0 to 3 days old, especially from women who conceive without assisted reproductive technology. Collecting embryonic cells from these women has moral, ethical and technological challenges, and many women do not know they are pregnant in the first week of a pregnancy, Orzack says. Even collecting such data from an embryo created with assisted reproductive technology is problematic: Taking a single cell from the first hours or days of development could endanger the embryo.

Navara notes that researchers could design a similar study based on fetus DNA extracted from its mother’s blood. These tests could provide sex data on fetuses as young as 9 weeks old from women who are not in high-risk pregnancies and offer more clues to how the sex ratio fluctuates from conception to birth.

“Sex is a fundamental difference in biology that starts getting created at conception,” Orzack says. The new study cannot answer all questions about this difference, but he says he hopes it creates a template for new investigations into the first nine months of development.