Elizabeth Jordan Carr, the first infant born after in vitro fertilization in the United States, turned 40 on Dec. 28, 2021. During those 4 decades, the technology and the culture surrounding fertility have radically changed.

“She was really instrumental in putting the spotlight on fertility treatments for those who were unable to conceive and to have the media understand that there are couples who need assistance,” Jane L. Frederick, MD, FACOG, medical director at HRC Fertility in Laguna Hills and Newport Beach, California, told Healio.

“When Elizabeth Jordan Carr was born, we were only fertilizing an egg and a sperm in a test tube for 48 hours, and then that was it. We really didn’t have any technology about how to grow an embryo beyond that,” Frederick said.

The technology’s evolution

In the 1950s and 1960s, scientists began fertilizing mouse and rabbit embryos in the laboratory and transferring them into the womb. These animals then carried their offspring to term and experienced live births.

But there were challenges in achieving the same results in human beings. Instrumentation such as more powerful microscopes were necessary to analyze cell tissue. Also, researchers had to develop the media where the cells would grow and multiply.

Jane L. Frederick

“There was a lot of trial and error during that time in trying to figure out what the cells really needed,” said Frederick. “Glucose, carbon dioxide, oxygen — everything has to be equilibrated to simulate what would occur in the human body.”

Cultures now can sustain embryos for up to 5 days, allowing them to grow to a hundred cells. Doctors can then biopsy one cell out of that hundred for a clear idea of each embryo’s chances for success.

“We can genetically test for all 24 chromosomes, which helps me figure out which embryo is healthy enough for transfer and which one is not,” Frederick said. “I can better select the right embryo for implantation instead of randomly selecting one and hoping for the best.”

When patients have family histories or previous births with genetic disorders such as cystic fibrosis, Tay-Sachs disease or hemophilia, doctors can select embryos unaffected by those genes.

“If the disease has a gene related to it, we build a probe for that specific gene, and I can give them a healthy child on their next pregnancy,” Frederick said. “This has greatly helped a lot of couples who suffer from genetic disorders.”

This preimplantation genetic testing also eliminates the need for multiple implantations and resulting twin, triplet and quadruplet births, which are more prone to preterm births and related risks for developmental disorders.

“The uterus doesn’t handle multiple births very well,” Frederick said. “We really try to limit the number of multiple births that we are producing through IVF, and the way we do that now is to transfer a single healthy embryo.”

While this is going on in the lab, the uterus needs to be prepared to receive the embryo as well. In the 1950s, studies described how the uterus responds to different levels of estrogen and progesterone during the menstrual cycle.

“That follows through to what I do today, which is sequentially preparing the uterus with estrogen of different levels and then adding progesterone to help implantation,” said Frederick. “That technology was very critical. There’s a lot of synchronization between the embryo and the uterus. It has to be right, or it doesn’t work.”

There have been developments with low sperm counts, too. Previously, clinicians would place the sperm next to the egg in the test tube and hope it would fertilize. Intracytoplasmic sperm injection, however, takes a single sperm and injects it directly into the egg.

“It’s not 100%. We need to understand the genetics of the sperm and why it doesn’t always produce a fertilized egg. We don’t have a lot of information about male infertility,” Frederick said.

“We have limited ability to study the DNA in the sperm head. There’s still some selection there. Our technology is getting closer to that, but it’s not there yet,” she added.

Evolving motivations for treatment

The demographics of the patients seeking treatment have changed over the decades as well.

“I used to just treat heterosexual couples who were infertile back in 1990 when I started,” said Frederick, noting that one in eight couples have fertility problems and that there are many reasons why women seek fertility treatment now.

“We noticed that women are waiting until their late 30s to try to have their first baby, and many of them are waiting until their 40s,” she said. “A lot has gone into how we can help preserve the fertility of the younger patient.”

Many women choose to freeze their eggs — a technology that has only been around for about 15 years, Frederick said. Some of these women do so because they do not have a partner for a family yet and hope to in the future. Also, women who are cancer patients may freeze their eggs before chemotherapy and radiation therapy may cause sterility.

“We are much better able today to screen for cancer. We have a lot more cancer survivors than we did 30 years ago, and because of that I’m seeing more referrals for patients who want to freeze their eggs. And then they’ll come back when they’re survivors,” Frederick said.

Frederick also sees many same-sex couples.

“I’ll see two men using a donor and a surrogate to have a family. I see reciprocal IVF patients, with two women, where one has an egg harvested and the other carries the embryo so they both can participate in pregnancy,” she continued. “The LGBTQ community is aware that they do have options to build a family.”

Economic and social barriers

Technology has enabled Frederick and her colleagues to treat a broader range of parents than was possible when treatment began 4 decades ago. Yet hurdles remain.

“Hopefully, the cost of procedures will go down so everybody can have access to the treatment,” said Frederick. “That’s really the issue I see right now. It’s cost-prohibitive for a lot of patients.”

Insurance companies have increased coverage for this treatment since it first began, and Frederick said that approximately 30% of her patients have coverage for infertility.

“It was 0% when I first started,” she said. “However, the definition of what they cover varies.”

Some coverage may stop with the initial consultation, while other coverage will fund the full treatment cycle. Frederick said that she and her colleagues have lobbied state legislatures to make infertility treatment a fully covered benefit.

“Many insurance companies don’t consider it a disease. It’s just a condition that you have. But we really want insurance companies to acknowledge that everybody should have access to treatment,” she said.

Employers such as Facebook, Apple and Disney offer infertility coverage, with Facebook, Apple and Google offering egg freezing for new hires, Frederick said.

“They see that as an opportunity to hire more women in their 30s. I think that’s incredible. We need to get more employers to understand that it really isn’t a choice and that our biological clock is real,” she said.

While insurance and companies have been more receptive to providing fertility treatment, society has become more accepting as well.

“It used to be very hush hush. You didn’t tell your neighbors or family how the baby was born or how you went to infertility treatment,” Frederick said. “Nowadays, children are aware that they were born through IVF. Mom and dad are okay with discussing it.”

Research has shown that when parents are honest with their children about how they were conceived, those children and families have a more positive outlook on infertility treatment, Frederick said.

“When we have our big baby reunion every year, these couples come back to visit us, and it’s so great to see them. And the first thing they say to me is, ‘Wow, all these people went through infertility like I did,’” she said.

“It’s very common, and people definitely feel more comfortable,” she continued. “I hope that brings hope for couples to say, ‘Well, so and so had treatment. Let’s go talk to the doctor and see what’s available.’ That will open up doors for patients who really need to understand why they’re not getting pregnant and how we can help them.”