Louise Brown’s Birthday and the Evolution of IVF

By Dr. Joseph A. Hill, a fertility specialist in Progyny’s Provider Network and CEO of Fertility Centers of New England

Dr. Joseph A. Hill

On July 25, Louise Joy Brown, the first baby born utilizing in vitro fertilization (IVF), turns 40. Louise’s parents, John and Lesley Brown, were referred to Patrick Steptoe, a British Obstetrician and Gynecologist who was an early pioneer of laparoscopic surgery for infertility. Steptoe had partnered in 1966 with Robert Edwards, an English biologist and physiologist with a special interest in human embryology. In 1969 Edwards was the first to achieve human fertilization in vitro. He won the Nobel Prize in Medicine in 2010 for his pioneering efforts in human embryology, which enabled the clinical development of IVF.

The innovations and seemingly miraculous accomplishments of Steptoe and Edwards were built on the work of many men and women going back to the 1890s through the 1930s, 40s, and 50s. Others in Australia, Europe, and the United States were working on IVF contemporaneously with the Steptoe and Edwards Team. Howard and Georgeanna Seagar Jones achieved the first baby born in the United States in 1981 using ovulation induction with hMG, which is a medication with hormones to stimulate your ovaries. This procedure allowed the recruitment of more than one egg, unlike the natural cycles being monitored by Steptoe and Edwards.

Science Photo Library — ZEPHYR/ Brand X Pictures/Getty Images

In the early 1980s there were very few IVF Centers in the world; today there are thousands with over 450 in the U.S. alone. Pregnancy success rates resulting in a baby have gone from single digits in the early days to well over fifty percent today. Furthermore, multiple pregnancy rates have decreased from double digit numbers to less than five percent without significantly compromising the live birth rate.

These phenomenal success rates are due to the many innovations that have snowballed since Louise Brown’s birth. Tremendous accomplishments, both clinically and in the laboratory, have occurred. Ovarian stimulation protocols have evolved with refinement of ovulation induction agents and protocols allowing recruitment of better quality eggs. Hospital based surgeries have been replaced with minimally invasive outpatient procedures like ultrasound guided oocyte retrieval and embryo transfer.

Epididymal (which relates to the tube near the upper testicle that transports sperm) and testicular sperm extraction methods have been discovered which allow many men with azoospermia, which is the absence of viable sperm, the ability to father children. The serendipitous discovery of intracytoplasmic sperm injection introduced the field to the term, ‘ICSI’ which has revolutionized fertilization methods by allowing the direct injection of sperm into eggs. The development of embryo culture media and embryo culture systems have evolved allowing embryo development to five and six days after fertilization in vitro facilitating the selection of the best quality embryo for transfer. Extended culture has further enabled embryo biopsies for DNA amplification which set the stage for preimplantation genetic testing (PGT) for aneuploidy (PGT-A), chromosome structural rearrangements (PGT-SR), and single gene mutations (PGT-M) offering the prevention of many debilitating and lethal diseases. Inheritance of mitochondrial diseases may be eliminated by third party reproduction where donor egg cytoplasm is fused with the nucleus of an otherwise affected egg prior to fertilization in vitro.

Cryopreservation techniques of gametes, embryos and reproductive tissues themselves now enable the potential of preserving fertility which is especially important for those needing chemotherapy or radiation therapy to treat cancer and other illnesses requiring reproductive toxic therapies. Scientists in Denmark have begun building an artificial ovary in mice that may one day be applicable to restoring fertility in women following cancer therapy.

Donor eggs and the use of gestational carriers have enabled thousands of otherwise childless people the opportunity to build healthy families.

Better definition of the implantation window is another exciting area of current investigation. Further understanding endometrial receptivity will enable the optimal time for embryo transfer potentially leading to even higher chances for a successful pregnancy.

And the future, what does the future hold? Determining how, why and when things happen. How does a day five blastocyst make a person? This is the fundamental question in biology. The answer undoubtedly lies within our chromosomes, in our genes and in the coded proteins that make us, you and I, us. Today, the precise mechanisms remain allusive, however, one thing is sure, the men and women who discover these answers will be standing on the shoulders of giants, not only those of Steptoe and Edwards but on those of the many men and women who have gone both before and since their marvelous achievement of giving John and Lesley Brown their daughter, Louise.