Two weeks before her 48th birthday, Eboni Camille Chillis lay in a hospital bed, ready to give birth to her first child. As she nervously waited for the doctors to begin a cesarean section, she put on a playlist she had made for the occasion. It consisted of songs she found calming and empowering, such as Diana Ross’s “I’m Coming Out,” and “Lovely Day,” by Bill Withers. With her phone next to her ear, she sang along. A few nurses joined in too.
Chillis had always wanted to be a mother. In her 20s and 30s she’d expected the rom-com ending. “I would fall in love, get married, have a baby,” the Atlanta-based educator and entrepreneur told me. “And it didn’t happen that way.” When the pandemic forced her to slow down and reflect, she committed to having a child on her own. She was in her mid-40s. Based on her age and test results, she was told that the odds of conceiving with her own eggs were less than one percent, which led her to seek an egg donor. For a year she scrolled through profiles of egg and sperm donors, scrutinizing their baby photos, medical history, favorite films. After finding donors who felt like the right fit, it was time to prepare her uterus for an embryo transfer. She gave herself daily progesterone injections for two weeks before the procedure and continued the shots throughout her first trimester.
Last January, Chillis’s daughter was born, making her debut as Stevie Wonder’s “Isn’t She Lovely?” played. A nurse placed the baby on the new mom’s chest, and her tiny mouth immediately began searching for Chillis’s breast. When she latched, the uncertainty of the preceding years dissolved, and Chillis thought, We’re going to be OK.
Chillis is part of a shift that’s been under way for decades: More and more, people are postponing parenthood. In the United States in 1970, the average age of a woman giving birth for the first time was 21.4. By 2021, it was 27.3. According to the Centers for Disease Control and Prevention (CDC), from 1985 through 2022 the birth rate for women ages 40 to 44 rose almost continuously, from four to 12.5 births per thousand women. For women over 45, the rate remained low in 2022, at 1.1 per thousand women, but represented an increase of 12 percent from the previous year. (CDC data do not reflect that people who give birth have a range of gender identities.) Although the numbers vary by country, many parts of the world show the same trend.
To be clear, some women have always had children later in life. In 1940 the birth rate in the U.S. for women 40 to 44 years old, and even for women over 45, was slightly higher than it was in 2022. But at the time, these births were typically the mother’s third, fourth, or fifth child.Today people are starting families later and in some cases without partners. It’s a familiar story: People, often with access to more reliable contraception, prioritize education and careers—not to mention footloose freedoms—before taking on the all-consuming responsibilities of child-rearing. Greater opportunities for women and evolving gender roles have been key factors. Meanwhile, assisted reproductive technologies such as in vitro fertilization (IVF) have enabled people to have children in circumstances where it previously would have been difficult. The result has been at least 12 million children born worldwide through IVF and a profound transformation of human reproduction. Now scientists are pursuing new lines of research that appear poised to revolutionize it even more.
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THE FIRST BABY CONCEIVED through IVF was born on July 25, 1978, in Oldham, England. The procedure involves fertilizing an egg with sperm in a petri dish, creating an embryo that can be transferred into a person’s uterus. It was initially used in cases of blocked fallopian tubes but proved capable of addressing other infertility issues. At the time referred to as “test-tube babies,” children conceived by this method inspired fascination and alarm in the media and the public. Fears ranged from the possibility of birth defects to religious concerns about intervening in the reproductive process. But it didn’t take long for the procedure to become common and widely accepted.
In some cases, a patient’s eggs were not viable, due to age or other factors. So the medical field started exploring egg donation. The first successful egg-donor birth was reported in 1984. On February 3, a headline on the front page of the Los Angeles Times blared: “Woman Bears Donor’s Baby”—phrasing that suggests some confusion about who was the mother. In March 1992, Jonie Mosby Mitchell, a former country singer, gave birth at 52 using an egg from a younger woman. At the time, she was reported to be the oldest mother in the U.S. to have a baby through IVF.
Mitchell already had four children from a previous marriage and an adopted daughter with her new husband, but wanted a baby with him too. When I spoke with her recently, she remembered reading in the newspaper about Mark Sauer, then a physician at the University of Southern California who was a pioneer of egg donation. She reached out to Sauer about having a baby at her age, and she recalled his response was, “You know, Jonie, there’s no reason in the world you can’t have one.” She became a patient of Sauer’s and delivered a son, Morgan. The birth was covered widely in the press. “Everybody was tickled,” she said.
Successful egg-donor pregnancies confirmed that age was not necessarily an impediment for the uterus, even after menopause. The challenge lay in the ovaries, which age at a markedly accelerated rate compared with other organs in the body. Ovarian reserve refers to the quantity and quality of a person’s eggs. Over time, the number of eggs sharply decreases, and those that remain accumulate DNA damage and chromosomal problems, making fertilization more difficult and miscarriage more likely.
Sauer co-authored a series of articles in high-profile medical journals about his early IVF work, culminating in a 1993 Lancet paper titled “Pregnancy After Age 50.” The ensuing media attention drew droves of new patients from around the world. Although he faced some backlash, he said it was gratifying to help people realize their dreams of parenthood. He recalled friends of his own children coming to his house and saying, “My mom said to tell you thank you for my brother.”
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THE COMPARATIVELY RAPID AGING of the ovary has long been a mystery. There are different theories as to why. “People talk about how there must be some evolutionary advantage to menopause, perhaps,” said Rebecca Robker, a professor of biomedicine at the University of Adelaide in Australia who studies female reproductive biology. “You know, like the grandmother hypothesis. Is it beneficial for societies to have these older, wise women assist in the families?” Another theory is that most humans didn’t live much past 40 before medical advances lengthened life spans. But in that case, why do other organs remain healthy for longer, and why does sperm production continue?
The aging of the ovary itself is distinct from the decline in egg quantity and quality, but the two are related, albeit in ways scientists don’t yet fully understand. And both relate to hormone production, which affects not just fertility but nearly all aspects of health, from cognitive functioning to bone density.
Egg donation as well as the increasingly popular practice of egg freezing can enable older women to use younger eggs, whether their own or someone else’s. But what if scientists could figure out a way to slow down or turn back the biological clock, so that women could prolong their fertility while also reducing the negative health effects that accompany ovarian aging?
In recent years, a growing number of researchers have begun to pose that question. One key discovery was made in 2016 by Francesca Duncan, a professor of reproductive science, and her team at Northwestern University. They noticed that the ovary becomes stiffer, or “fibrotic,” over time. “The ovary’s very dynamic,” Duncan said. There’s a lot going on, including the growth of follicles (the structures that contain and nurture immature eggs, or oocytes), the rupture of a follicle to release an egg with ovulation, and the death and reabsorption of unreleased oocytes.
All of this activity means that tissue is constantly getting repaired, which can lead to fibrosis—essentially, scarring. Duncan and other scientists, including Robker, have been investigating possible therapies that could “soften” the ovary and extend fertility. A 2022 paper in Science Advances, co-authored by Robker, reported that existing antifibrosis drugs restored ovulation in 15-month-old mice, comparable to humans around age 50.
David Pépin, a reproductive biologist at Massachusetts General Hospital, is investigating a different angle. He’s studying the little-known but important anti-Mullerian hormone (AMH), produced by follicles in the ovaries. He believes modulating AMH could, in effect, help switch fertility off and on. Pépin formulated a synthetic version of AMH that he’s tested on animals, including mice and cats. He discovered that at elevated levels, AMH prevents the activation of growing follicles. When a sufficient dose of the hormone is administered, he said, “you have very few follicles activate, and those that do are basically incapable of growing and maturing.” As a result, AMH could act as a contraceptive. (He’s developing a feline contraceptive to control feral cat populations, but it consists of a onetime injection, whereas the goal for humans is a daily pill.)
When treatment ceases, fertility may be restored and possibly even enhanced. The follicles resume growing, and because they’ve been accumulating for the duration of treatment, more follicles than usual grow concurrently. If someone with a dearth of eggs were to undergo IVF at that time, the odds of success could rise. AMH treatment could also interrupt some of that perpetual activity in the ovary, potentially diminishing the aging associated with it.
Scientists agree that no single solution will dramatically prolong fertility or ovarian health. But if research in several relevant areas bears fruit, it could add up to meaningful progress in the coming years. “We’re at a point in time when there’s a lot of eyes on this topic,” said Duncan. For example, the Global Consortium for Reproductive Longevity and Equality was founded in 2019 to support research and foster a global network of scientists and clinicians to study the subject. The organization has distributed more than $14 million to 48 researchers worldwide, including Duncan. They call their efforts “a moon shot initiative to tackle female reproductive aging.”
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EVERY MORNING, EBONI CAMILLE CHILLIS goes to the crib, hugs her baby, and thanks her for being her daughter. Although the path to parenthood was different from what she’d envisioned, Chillis has come to embrace it. “There’s a wholeness and happiness to me that I don’t know that I’ve ever experienced,” she said.
Other people who’ve had children through IVF later in life are similarly enthusiastic. “It is awesome,” said Susie Troxler, who gave birth at age 50, using a donor egg and her husband’s sperm after the couple tried to conceive on their own for almost a decade. “If it weren’t for that technology, we wouldn’t have been parents at all.”
Yet some researchers and clinicians add a note of caution about delaying parenthood, even as their own work has contributed to the shift. One of the biggest risks is that the joyful endings don’t always materialize. Sauer said that the high-profile success stories can obscure “the reality of how difficult it can be to achieve.” According to the CDC’s most recent data, the percentage of live-birth deliveries from IVF cycles by patients of all ages was 37 percent in 2020. The rate drops significantly for IVF patients over 40. (Using younger donor or frozen eggs improves one’s chances, of course, but there are still no guarantees.) IVF is a costly procedure, often not covered by health insurance. The successes may give people misleading reassurance that they can always wait.
The risks of aging apply to men as well. “Men’s sperm quality declines significantly over 40 and continues to decline,” said Pépin. Although these sperm may still fertilize an egg and result in a successful pregnancy, DNA damage can result in adverse health outcomes for a child.
There are many reasons people postpone having children, and one of them is lack of social support. Robker noted that with more family-friendly government policies—affordable childcare and paid leave—some might choose to start their families at a younger age. “I can’t do anything about the policies, so I’m working on how do we help people have the best ovary health for both their fertility and their overall health,” she said.
Beyond ovarian health, significant research is under way on more futuristic concepts. A process known as in vitro gametogenesis (IVG) involves creating gametes from stem cells—for example, deriving an egg from another kind of cell, such as a skin cell. IVG could enable same-sex couples to have children with genes from both parents; it could allow more than two people to reproduce together. There’s also the possibility of growing a fetus outside of a uterus in a synthetic womb.
Robker expects reproduction to change dramatically in the coming years. “People feel very, very passionate about having biological children,” she said. “So that is pushing the boundaries on the development of new technologies that can facilitate generating embryos.”
IVG and artificial wombs are likely still years, if not decades, away. But as these new tools evolve, vexing medical and ethical dilemmas are bound to follow. There are many risks, to be sure, yet there have already been many rewards from current reproductive technology: millions of parents who are grateful to have children when that hadn’t seemed possible. “She’s the light of our world,” Troxler said of her daughter, Lily. “She’s here when she’s supposed to be here, to do what she’s on the planet to do.”
Source: National Geographic