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22nd of November 2017

Science



20 Years Of Progress And Millions Of Babies: Milestones For Infertility

Advances made in the treatment of infertility over the past 20 years are impressive, ranging from radical new techniques to edit embryonic genes to incremental changes that improve IVF outcomes and are less invasive for patients. Treatment now extends to encouraging healthy lifestyles to improve fertility before trying to become pregnant. And societal attitudes have changed, too, with non-traditional families actively seeking advanced reproductive techniques (ART) to have babies. As the organization I founded celebrates our 20th anniversary, it seemed timely to review the field’s major milestones.

IVF – first live birth (July 25, 1978)

The major fertility advance begins within in vitro fertilization (IVF) and the successful birth of the so-called “test tube baby” Louise Brown. More than 60 failures beforehand serve as reminder that translating research to widely accepted medical practice takes time.

During IVF, a fertility doctor takes the eggs from the ovaries using a small needle and fertilizes them with sperm in a specialized lab. After fertilization, the eggs develop into embryos, and usually five days later the specialist re-implants the embryos back into the uterus.

More than eight million babies have been born worldwide using IVF in the last 39 years and innovations continue: egg retrievals performed vaginally instead of by laparoscopy, eggs injected with sperm for fertilization, embryos tested for genetic diseases, transferred on day five instead of day one or frozen for years, and 24-hour “live-cam” coverage to monitor cell division and predict the healthiest embryos to improve pregnancy rates and lower multiple pregnancies.

Embryo Freezing (early 1980s)

Freezing or cryopreservation helps make future ART cycles simpler, less expensive and less invasive than the first IVF cycle because ovarian stimulation and/or egg retrieval are not required. Once frozen, embryos can be stored for prolonged periods. While live births have been reported using embryos frozen for almost 20 years, only about half the embryos survived the freezing and thawing process and the live birth rate used to be lower with cryopreserved embryo transfer than fresh.

Egg donation (mid-1980s)

This major advance created a new option for women having problems becoming pregnant due to the quality of her eggs, often due to age. Eggs from younger women more often have normal chromosome numbers and increases pregnancy and live birth rates. A reputable agency can help match patients with egg donors who come from diverse backgrounds and choose whether the donor is known, anonymous or semi-anonymous.

ICSI (1991)

Approximately 70 percent of U.S. ART cycles now use intracytoplasmic sperm injection (ICSI) – where a single sperm is directly injected into each mature egg – to reduce the risk of no fertilization when there may be poor semen quality or a history of failure in a prior IVF cycle. Genetic counseling is advisable beforehand if inherited abnormalities are identified that may be passed from father to son. Overall, ICSI pregnancy and delivery rates are similar to conventional IVF insemination.

Preimplantation genetic diagnosis (PGD) (early 1990s)

PGD was first reported successfully in human IVF in 1989 to identify a sex-linked disorder and to choose an unaffected embryo. Since then the number of diseases that can be identified has grown dramatically. Today, tens of thousands of couples with the potential for having a child affected with a severe genetic disease have been able to avoid such an outcome through PGD.

Multiple Pregnancy (mid-1990s)

For years, IVF usually involved transfer of multiple embryos to increase the chance of a live birth. For some women, the result was multiple pregnancies and/or multiple live births – approximately 30 percent of IVF births are twins. Whether twins, triplets or more, multiples result in higher rates of miscarriages, premature delivery, serious, life endangering health problems (including to the mother), and permanent developmental issues. Embryo grading allowed better prediction of which embryo might be healthiest and best to implant, leading to elective single embryo transfer (eSET), now considered an IVF “best practice” for most, but not all, patients.

Preimplantation genetic screening (PGS) (late 1990s)

PGS is an embryology and genetics laboratories procedure performed before embryo transfer so doctors may pick one without an abnormal number of chromosomes. This increases the chances of selecting a healthy embryo that will develop into a healthy baby – important as birth defects occur in nearly 1 in 20 pregnancies. All couples are at risk for having abnormal embryos, with risk increasing significantly as a woman ages. An abnormal embryo almost always fails to implant, or may lead to miscarriage, fetal death later, stillbirth or a baby with abnormalities. The advantages and disadvantages of PGS remain controversial; read about the pros and cons here. PGS and PGD are now being renamed PGT for preimplantation genetic testing.

From 2010 – 2012, advances in preservation of eggs and embryos benefited women with cancer, single women delaying motherhood and family building.

Highlights include:

Vitrification (2008)

Two methods are used to cryopreserve embryos and sperm: conventional (slow) freezing and “vitrification” or flash freezing. Although some reports claim vitrification may have higher IVF success rates after thawing/warming, this is not true at all fertility centers. Each center will determine which method is best to use based on their experience and the developmental stage at which the embryos are frozen.

Egg freezing for cancer patients

Egg freezing was first used to help women facing medical issues like cancer where chemotherapy or radiation could permanently impact fertility, over 25 years ago. However, with the better result obtained with vitrification, now, more cancer survivors start or add to families through egg freezing, embryo freezing (not an option with immediate treatment needs), or experimental ovarian tissue freezing. Patients who are diagnosed with cancer should work closely with their oncologist and consult a fertility specialist as soon as possible to get information and make choices about egg preservation before treatment.

Egg preservation for single women (2012)

With the 2012 announcement by the American Society for Reproductive Medicine (ASRM) that egg freezing was no longer experimental, clinics began marketing these services to women concerned with declining fertility. Despite the rapid growth in egg freezing, age still matters and doctors generally don’t recommend the process for women over 38. Overall, the success rate of live births from frozen eggs has remained consistently fairly low – about 20 to 24 percent. Younger women have much higher success rates. For more, see The Hot Topic of Egg Freezing and What You Should Know.

Non-traditional Families (increasing since the 1990s)

Acceptance of infertility treatment for non-traditional families including single women and men and lesbian and gay couples has evolved over time. ART is now readily available to help family-building through a variety of options including reciprocal IVF or co-maternity for lesbian couples where one partner provides the eggs and the other partner carries the pregnancy, allowing both women to be physically involved in the pregnancy.

Gene Editing (2016)

Approved first for use in UK labs, a new technique (CRSPR) to edit embryonic genes may eventually lead to more effective infertility treatment and fewer miscarriages. It may eventually also help those with a family history of disease with a known genetic link such as muscular dystrophy through gene editing to make the embryos disease-free. Knowledge gained with the new technique may also prove helpful in treating different types of infertility. Some US labs began using the new technique in research studies this summer.

For the field of infertility, the medical and societal progress of the last 20 years has been nothing short of phenomenal – not to mention rewarding. Just think what lies ahead!

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