For many years, preimplantation genetic diagnosis (PGD) was the only term used for all genetic testing of the embryos. With the explosion of new technology in field of genetic testing, clinicians have introduced preimplantation genetic screening (PGS), which is used for screening genetic abnormalities in patients without known genetic disorders. The public commonly uses PGD and PGS interchangeably but they are not the same.

Preimplantation genetic diagnosis (PGD)

PGD is typically done in couples who are known carriers of genetic disorders or have a family history of genetic disorders. This test is done to look for a specific genetic abnormality or abnormalities that the embryo may carry. There are over 4,000 single-gene disorders but only about 200 disorders and some forms of inherited cancers (i.e. retinoblastoma and BRCA2) can be diagnosed using PGD-PCR

Here are some indications for PGD in single-gene disorders according to European Society of Human Reproduction and Embryology (ESHRE) data:

•   B-thalassemia
•   Cystic fibrosis
•   Huntington’s disease
•   Fragile X X-linked
•   Myotonic dystrophy
•   Spinal muscular atrophy
•   Neurofibromatosis type I
•   Duchenne’s muscular dystrophy
•   Marfan syndrome
•   Hemophilia A
•   Tuberous sclerosis

Preimplantation genetic screening (PGS)

Unlike PGD that test for specific genetic conditions, PGS looks at the overall chromosomes. PGS has been recently used to improve pregnancy success by screening embryos for abnormal number of chromosomes.

Humans have 46 chromosomes, in which 23 are inherited from our mothers and 23 are inherited from our fathers. But frequently, embryos do not have the correct number of chromosomes (aneuploidy) due to a variety of known and unknown reasons.

Embryos with aneuploidy will either stop developing in the early stages, cause spontaneous abortion if the embryo implants onto the uterus or in rare cases, a child will be born with abnormal chromosomes. According to a study by Munné et al., at least 40% to 60% of human embryos are abnormal, and this number increases to 80% in women 40 years or older.

By using PGS to screen for the correct number of chromosomes and to ensure only the normal embryos are transferred, the clinicians can try to increase the pregnancy success rates. Unlike PGD, PGS can be used for all patients, especially women with advanced maternal age or couples with reoccuring, unexplained abortions. PGS can also be also used to determine the sex of the embryo by looking for the X and Y chromosomes (XX for female and XY for male).

Picture shows blood chromosome analysis. (Left) A normal female with 46 chromosomes. (Right) A male with Down syndrome, three 21 chromosomes. Available at: http://geneticsandfertility.com/pgs-and-pgd-ivf/ (Accessed April 22nd, 2017)

Reference

Offt K, Kohut K, Clagett B, Wadsworth EA, Lafaro KJ, Cummings S, et al. Cancer genetic testing and assisted reproduction. J Clin Oncol. 2006;24:4775–82.

Moutou C, Goossens V, Coonen E, De Rycke M, Kokkali G, Renwick P, et al. ESHRE PGD Consortium data collection XII: cycles from January to December 2009 with pregnancy follow-up to October 2010. Hum Reprod. 2014;29:880–903.

Munné S. Preimplantation genetic diagnosis for aneuploidy and translocations using array comparative genomic hybridization. Curr Genomics. 2012;13:463–70.

The number of eggs needed to be retreived for IVF will largely depend on the quality of the eggs retrieved but the average number of eggs retrieved per cycle is between 10 to 14 eggs. The number of good quality eggs retrieved from the ovaries will influence the number of embryos suitable for successful transfer/implantation and subsequently achieving a successful birth.

How many eggs should be retrieved to have the best chance of a successful live birth?

In a 2011 UK study, researchers analyzed more than 400,000 IVF cycles done in the UK from 1991 to 2008 and found the rate of live births increased as the number of eggs increased to 15, plateaued between 15 and 20 eggs and steadily declined beyond 20 eggs. These results were reflective of a younger patient population (more than half were ages between 18 to 34 years) and the IVF cycles were done with fresh eggs retrieved from the patient.

The same study also created a chart using the data analyzed to predict live birth rates based on the age group and the number of eggs retrieved as shown below.

Image: Sunkara SK, et al.

As one can see, the predicted live birth rate peaked around 15 to 20 eggs in all the four age groups. The chart shows the predicted live birth rate decreasing as the age of the women increases, even when the number of eggs retrieved increased. Retrieving 15 eggs at the age of 40 years and over had similar predicted live birth rate as retrieving 2 eggs at the ages of 18 to 34 years. This shows the general decline in the fertility and the increasing difficulty of becoming pregnant as women ages.

In a 2013 Chinese study, researchers analyzed 2,455 women who undergone their first IVF treatment cycle from 2007 to 2011 and found the cohort that collected between 6 and 15 eggs had the best rates of live births. Like the 2011 UK study, this study is reflective of a younger patient population (study only analyzed women aged between 18 and 34 years) and the IVF cycles were done with fresh eggs retrieved from the patient.

So does this mean every woman undergoing IVF should be stimulated toward the retrieval of about 15 eggs?

A woman’s age is a strong predictor in the number of eggs retrieved after ovarian hyperstimulation. This is due to the natural decline in the woman’s ovarian reserve as the woman ages. For example, women over 40 years with maximal ovarian stimulation would have great difficulty producing 15 eggs, whereas a young woman with polycystic ovarian syndrome (PCOS) will often exceed this number, even with the mildest stimulation.

Giving higher doses of reproductive hormones during ovarian hyperstimulation to boost the number of eggs retrievable increases the risk for ovarian hyperstimulation syndrome (OHSS), increases the risk for possibility harming the endometrium, and may negatively affect the egg quality. As seen in the chart above, a 40-year-old woman with 15 eggs only has a predicted live birth rate of about 15%. The risk of adverse effects from maximizing the hormone doses in a 40-year-old woman to try to retrieve 15 eggs often outweighs the benefit of increased egg retrieval.

The goal of the fertility doctor is not solely focused on the number of eggs retrieved, but trying to retrieve “enough eggs” to have a successful birth. A clinician and the patient will need to balance the risks and benefits of aggressively stimulating the ovaries to maximize egg production to improve the success rate of a live birth. For a woman with normal ovarian function and less than 35 years of age, retrieving 15 eggs looks to be the magic number for the best chance of having a baby through IVF. For women who are older or have a complicated case, the number needed to retrieve will be individualized to their specific case.

Reference

Vaughan DA, Leung A, Resetkova N, et al. How many oocytes are optimal to achieve multiple live births with one stimulation cycle? The one-and-done approach. Fertil Steril. 2017; 107: 397-404.

Sunkara SK, Rittenberg V, Raine-Fenning N, Bhattacharya S, Zamora J, Coomaeasamy A. Association between the number of eggs and live birth in IVF treatment an analysis of 400,135 treatment cycles. Hum Reprod. 2011; 26: 1768–1774.

Ji J, Liu Y, Tong XH, Luo L, Ma J, Chen Z. The optimum number of oocytes in IVF treatment: an analysis of 2455 cycles in China. Hum Reprod. 2013; 28: 2728-2734.

In vitro fertilization (IVF) is a medical and surgical procedure that involves fertilizing the egg outside the woman’s body and transferring the resulting embryo back into the woman’s body. The procedure is a multi step process requiring medications to stimulate egg production in the ovaries, minor surgical procedures to retrieve the eggs and implant the embryo, and clinical monitoring by the fertility doctor throughout the process.

IVF is done over a period of two to four weeks. The duration of the IVF is called a cycle. For many women, one cycle of IVF may not be enough to successfully have a baby. The success rates of IVF vary depending on multiple factors (i.e. age and medical history) but the average number of IVF cycles needed before a successful birth is about three.

The Basic IVF Cycle

The basic IVF cycle is composed of ovarian stimulation, retrieval of the matured eggs (aka oocytes), fertilization of the eggs, and the transfer of the embryo into the uterus.

Women naturally produce one mature egg during their monthly menstrual cycle. However for IVF, the procedure requires multiple mature eggs to increase the chances of successful fertilization and developing into healthy embryos. Ovarian stimulation is used to stimulate the ovaries to increase the number of mature eggs produced. This is done by administering reproductive hormones to the patient. These hormones are typically given as daily subcutaneous injections at home. During this time, the doctor monitors the development of the oocytes via ultrasound to determine when the eggs are mature for retrieval.

Once the eggs are matured, the retrieval procedure begins. The retrieval of mature eggs involves a minor surgical procedure with anesthesia where the fertility doctor will use a medical device to retrieve the mature eggs from the ovaries.

After the eggs are extracted, they are immediately transferred to the lab, processed, and fertilized with the partner’s sperm by the embryologist. About three to five days after fertilization, the embryologist determines which embryos are the best suited for transfer into the woman’s uterus.

The last step in IVF is to transfer the embryo into the woman’s uterus for implantation. This involves a short, minor surgical procedure where usually one or two of the best quality embryos are inserted into the uterus. After the transfer, the embryos implant itself to the uterus and the pregnancy is underway.

The Cost

As one can imagine in a complex procedure like IVF, the cost of undergoing a cycle can be expensive. Many times, insurance only partially covers or does not cover the procedure at all. The cost of IVF will vary depending on many factors (i.e. the clinic, geographic location of the clinic, diagnostic tests) but the average total cost including medications in the US is between $20,000 and $25,000 per IVF cycle. As most women will undergo multiple cycles of IVF, the cost can quickly climb.

IVF can be an expensive and challenging procedure to go through but for many infertile couples, this provides the best possibility for conceiving their own child.