A Brief History of the Developments that Enhance Fertilisation in Vitro

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A Brief History of In-vitro Fertilisation

The study of human reproduction has always been filled with ethical and scientific issues that at first impeded the research into treatments for infertility. However, during the 1960s and 1970s, our understanding of the process that occurs during human oocyte fertilization increased to the point where in vitro fertilization (IVF) with human oocytes became feasible.

A Brief History of the Developments that Enhance Fertilisation in Vitro

This knowledge ultimately was the catalyst for the widely-praised very first live birth of the term “test tube baby,” Louise Brown, in England in the year 1978. In this IVF sentinel birth, the mother experienced an unnatural menstrual cycle.

Doctors removed a single pre-ovulatory Oocyte from her ovary and fertilized it in vitro followed by the transfer of the eight-cell embryo to her uterus.

Three years after, the first IVF baby was born in the U.S., and the 15th globally was born. In this instance instead of relying on the single oocyte which could be naturally produced and the mother was treated for a few days with menopausal gonadotropin to stimulate follicles within the ovary, which produced the oocytes.

Following this procedure, known as controlled stimulation of the ovary (COS) doctors removed the oocytes that were pre-ovulatory which were fertilized in vitro, and transferred the day 3 or 5 embryos into the mother’s uterus.

In 1985 an initial IVF baby born in Missouri came to the couple who had undergone IVF through Washington University and delivered at the present Barnes-Jewish Hospital. Since then the process of IVF continues to develop at a remarkable speed.

At the present, IVF accounts for millions of births around the world and 1 to 3 percent of births that occur each calendar year across Europe, the U.S., and Europe. The rising need for fertility treatment is driving research and development of technology to improve IVF treatments and their success.

In the majority of IVF cases, couples who are infertile are treated to have an unrelated genetically. But, couples are taking part in IVF to ensure that their embryos can be tested genetically to prevent the transmission of single-gene mutations linked to mortality. Furthermore, the using donor sperm and Oocytes are becoming more prevalent as well as women who aren’t able to conceive can now use gestational carriers.

Controlled Ovarian Stimulation

The first studies of IVF conducted on women going through natural menstrual cycles produced an average of 0.7 Oocytes per retrieval, with a 6.6% cycle rate of pregnancy. In the 1980s, researchers from the Jones Institute in Norfolk, Virginia began injecting females with gonadotropins to stimulate ovarian follicles that had multiple ovarian cells to produce Oocytes.

These oocytes then became fertilized in vitro and the most healthy embryos were implanted into the uterus of the woman. This introduction to controlled ovarian stimulation (COS) enhanced the average yield of oocytes to 2.1-2.6 and the average rate of pregnancy up to 23.5 percent during 1982, and 30 percent during the year 1983.

In the beginning, Human chorionic gonadotropin (hCG) was utilized to trigger ovulation as it’s physiologically similar to luteinizing hormone. It grows rapidly during a natural cycle to induce ovulation. At the beginning of IVF procedures, the primary issue was premature ovulation which would render retrieving oocytes difficult despite meticulous AND labor-intensive COS. But, two advances in IVF procedure, such as the use of gonadotropin-releasing hormone (GnRH) antagonists in the 1980s as well as GnRH antagonists as of 2001 allowed it to be possible to avoid premature ovulation as well as effectively control the retrieval of oocytes.

There are many different regimens of medication available that all adhere to the same principle injectable medicines increase the production of endogenous hormones, allowing multiple ovarian follicles that produce numerous oocytes during the time of retrieval.

Ovarian Hyperstimulation Syndrome

Two issues occurred due to the administration of supraphysiologic doses of gonadotropins. To increase the chance that a woman will become pregnant with a single fetus that will live to the fullest doctors started fertilizing multiple oocytes and placing multiple embryos. This can result in women carrying twins, or higher-order multiple fetuses, which puts the fetuses at risk of having a small birth weight and premature birth.

The second and most severe iatrogenic consequence of the stimulation of the ovary is called ovarian hyperstimulation syndrome (OHSS). OHSS is a condition that occurs when the ovaries get excessively stimulated and later either stimulated by injecting hCG to trigger Ovulation, or through the endogenous growth in hCG when a woman becomes pregnant. OHSS is defined by hemoconcentration resulting from leaky vessels as well as third spacing of fluid which can cause ascites as well as electrolyte dysfunctions. The signs can range from mild abdominal discomfort to renal failure, and even death due to the thromboembolic process or damage to the end organ.

Despite the extensive study on the cause, the exact mechanism behind COS remains unclear, but it is reported to be experiencing an increase in incidence due to an increase of follicles developing and high levels of estradiol that is created by the female ovarian follicles.

To address this issue in 1979, doctors began taking a close look at COS by measuring the levels of serum estradiol and transvaginally testing ovarian follicles to identify risks. The identification of patients at risk allowed doctors to take preventative steps including adjusting medications accordingly and monitoring the symptoms more often.

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