Preimplantation Genetic Screening

Preimplantation Genetic Screening

A woman’s fertility and the quality of her eggs progressively diminish with age, making it harder to become pregnant. The natural increase in the rates of genetic mutations in the eggs greatly contribute to the loss of egg quality. This lead to the development of preimplantation genetic screening (PGS) to help improve IVF outcomes by screening for embryos with chromosomal abnormalities and only transferring embryos that are normal therfore increasing chances for live births.

So what is PGS?

PGS is the process of screening the embryos for the correct number of chromosomes and for structural abnormalities in the chromosomes. On day 3 or day 5/6 after the egg is fertilized, the embryologist will take out genetic material from one or more cells in the embryo to test for any chromosomal abnormality. There are many different kinds of techniques used for PGS and each technique has different levels of accuracy and limitations. The most commonly used technique today is PGS 2.0, where genetic material is removed from the cells on day 5/6 (blastocyst stage) when more genetic material is available. PGS is widely used today to help improve the IVF outcome in patients with poor prognosis (i.e. older women or woman with history of multiple miscarriages) and to help select the sex of the child.

What are some concerns with PGS?

Although there are many benefits of PGS as it can test for chromosomal abnormalities of the embryos before the embryo transfer, there are some mistaken thoughts about PGS we need to know:

  • PGS primarily examines the number of chromosomes in embryo. This only allows detecting for chromosomal abnormalities rather than specific genetic abnormalities. Preimplantation genetic diagnosis (PGD) is used to describe testing for specific genetic disease, usually single-gene defects like cystic fibrosis and Tay-Sachs Syndrome. There are lots of diseases that are linked to abnormal chromosomal structure but specific gene mutations cannot be reliably detected with PGS.
  • PGS is not a reliable predictor for live birth of a chromosomally normal baby. Patients with normal PGS results can experience miscarriages and embryos with abnormal PGS results can progress to a live birth of a chromosomally normal baby. This is due to mosaicism, a normal condition in which there is the presence of two or more populations of cells with different genotypes in one individual. This means that the chosen cells are not 100% representative of all the cells in the embryo.
  • PGS can cause damages to the egg. The techniques used in PGS to remove the genetic material can cause some damages to the remaining cells and may reduce the success rates of implantation.
  • Not much data to support that overall IVF outcomes are improved. There is limited evidence to show that using PGS in patients with “advanced age”, often older than 37 years of age in many programs offering PGS, show IVF outcomes were improved. Patients who are older have a greater percentage of their eggs having chromosomal abnormalities, which would makes them the perfect candidates for PGS. However, the available data does not seem to support that reasoning.
Who might benefit from PGS?

Patients most likely to benefit from PGS are patients with a history of multiple miscarriages and cases of male infertility where chromosomal abnormalities or abnormal chromosomal structure are likely the reason for the difficulty in becoming pregnant. For patients who are using PGS for “advanced age,” the available data does not strongly support the use of PGS to improve IVF outcomes and may not be cost-effective as PGS can be expensive and are usually not included in the price of the IVF cycle.

The use of PGS to select the sex of the child is a controversial topic and this has lead to restrictions on the use of PGS in some countries by requiring additional documentation to justify using PGS. The degree of restriction is different depending on the country. In some countries, the lack of enforcement of the restrictions make it possible to use PGS for sex selection even though it is not allowed.

There are new PGS techniques currently being developed to improve the accuracy of the screening and make it less invasive when removing the genetic material from the embryo. For those who plan on using PGS, one should inquire whether PGS 2.0 is being used by the clinic and to fully understand the limitations of PGS.




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Gleicher N, Orvieto R. Is the hypothesis of preimplantation genetic screening (PGS) still supportable? A review. J Ovarian Res. 2017;10:21.

PGDIS Newsletter. PGDIS Position Statement on Chromosome Mosaicism and Preimplantation Aneuploidy Testing at the Blastocyst Stage. Chicago:PGDIS Newsletter;2016.

Handyside AH, et al. Pregnancies from biopsied human preimplantation embryos sexed by Y-specific DNA amplification. Nature. 1990;344(6268):768–770.

The difference between PGD and PGS

The difference between PGD and PGS


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: (Accessed April 22nd, 2017)



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.


How many eggs are needed to be retrieved for IVF?

How many eggs are needed to be retrieved for IVF?

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.




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.


What is IVF?

What is IVF?

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.

Why go to Asia for fertility treatment?

Healthcare in Asia has grown to prominence in recent years with the development of world-class facilities staffed with highly qualified healthcare professionals who are often trained abroad in the US and Europe. While these Asian healthcare facilities may not have the same level of reputation or the years of experience as many of the older medical institutions in the US and Europe, they often have better facilities equipped with state-of-the art medical technology, staffed with doctors trained abroad at reputable US and European medical institutions, and are internationally accredited.

US and Europe have been the dominant players in the development and expertise of infertility treatment since the beginning but many Asian countries are now prominent players in the fertility world and have made significant contributions to the field. The first egg-freezing center in the world was developed by a Korean fertility clinic and Asia is the leader in the number of IVF cycles done today.

With the experience and high quality of medical services provided in Asia today, it can be more cost effective to travel to Asia for fertility treatments at a fraction of the price than paying almost double in western countries. Going abroad for fertility treatment is not for everyone, but it can be a great option for some patients.

There are three main benefits to traveling abroad for fertility treatments: cost, minimal wait times, and having a vacation.

The lower healthcare cost is the biggest benefit for considering IVF treatment abroad. The average cost of a single IVF cycle including medications in the US is between $20,000 and $25,000. In Asia, the average cost of a single IVF cycle including medications is usually no more than $10,000. As most women will undergo multiple cycles of IVF before having a successful birth, the savings from the lower cost can become substantial.

The long wait times and the frustration of scheduling an appointment with the doctor or clinic is unfortunately a common occurrence in healthcare, especially in the US. In Asia, there are many clinics where you can just walk in to receive a consultation and scheduling an appointment to see a doctor occurs in a matter of days. This provides a flexibility that works with the patient’s schedule rather than the clinic’s schedule; something not commonly seen in the US.

The last benefit of considering IVF treatment abroad is the ability to make your medical trip into a vacation. Many of the clinics in Asia are located in major travel destinations. As the IVF process can be stressful and emotionally challenging, you can also use the trip as vacation to help reduce the stresses of the IVF treatment.

Going abroad for fertility treatment is not for everyone and there are disadvantages to consider. However, for patients with the right circumstances, going abroad can be a cost-effective way to undergo fertility treatment with some of the top fertility clinics in the world.