fertility Archives

Egg Freezing (Oocyte Cryopreservation)

Egg freezing or oocyte cryopreservation refers to the freezing of eggs (oocytes) to sub-zero temperatures to stop its biologic activity, keep it in a frozen state, and preserve them for future use. When the eggs are thawed at a future point in time, they resume normal function and can be fertilized.

A woman’s fertility naturally diminishes over time as the quantity and quality of the eggs decreases. Before 2012, egg freezing was still considered an experimental procedure for preserving fertility and not widely available. Only embryo freezing was available to the public for those interested in preserving fertility. Today, egg freezing is quickly becoming a sought after procedure for those interested in preserving their fertility for personal reasons. Egg freezing enables the preservation of the woman’s fertility by freezing her eggs before the quantity and quality of the eggs become low.

Who should consider egg freezing?

The demand for egg freezing is rapidly expanding. It is commonly used in egg donations and in women with cancer to preserve their fertility as cancer therapy often causes infertility.

The American Society for Reproductive Medicine (ASRM) lists the following cases when egg freezing is indicated:

Immediate threat to fertility because of chemotherapy or pelvic radiation therapy
Surgery associated with risk of damage to the ovaries
Ovarian disease (e.g., endometriosis) with risk of damage to the ovaries
Risk of premature ovarian senescence because of Turner’s syndrome (45,XO), the fragile X syndrome, or a family history of premature ovarian failure
Genetic mutation requiring oophorectomy (surgical removal of ovaries)
Failure to obtain sperm by means of testicular sperm extraction on the day of oocyte retrieval
Excess oocytes during in vitro fertilization along with ethical objection to or program specific restrictions on fertilizing more oocytes than will be transferred during one cycle
Preservation of donor oocytes
Preservation of fertility to delay pregnancy for personal reasons.

Recently, the use of egg freezing to preserve fertility in healthy women due to career advancement and life planning reasons have been rapidly increasing.

The public attention for egg freezing first hit headlines when Facebook and Apple announced that they would provide insurance coverage for the cost of egg freezing as an employee benefit. Egg freezing can provide women with more flexibility to pursue educational or career goals first while preserving their fertility for a later time.

To read more on the best time to do egg freezing, read here.

How is it done?

Egg freezing begins with the stimulation of the ovaries to produce mature eggs. The ovaries are stimulated once menses begins with injections of reproductive hormones for up to 2 weeks. The fertility doctor monitors the maturation of the eggs during this time using ultrasound to determine when the eggs are ready to be collected.

Once the fertility doctor determines the eggs are ready for collection, hCG (reproductive hormone) is administered to stimulate the final maturation process. About 34 to 36 hours after hCG is given, the woman undergoes a minor surgical procedure while being mildly sedated to collect the matured eggs. The collected mature eggs are then processed, frozen (typically by vitrification), and stored in liquid nitrogen at -196 degrees Celcius.

How many eggs do you need to freeze?

There is no exact number of eggs a woman should freeze in a cycle. The number of eggs collected will depend on the age of the woman, health status, ovarian reserve, and the protocol used at the IVF center. Typically 10-15 eggs are collected per cycle and these can be split into batches of 5 or 6 eggs to be used for more than one cycle. You can read more on the optimal number of eggs to retreive for IVF here.

How long can the eggs remain frozen?

There is limited data regarding the effect of storage time on egg viability and rate of live birth. One study in 2009 by Parmegiani et al. found there was no difference in the live-birth rates between fresh eggs and frozen eggs frozen for 48 months. The longest storage time for frozen eggs that resulted in a live birth was 14 years and 6 months.

Are pregnancy rates for using frozen eggs different from fresh eggs?

Many studies have demonstrated the use of frozen eggs have similar pregnancy rates to that of fresh eggs. The use of frozen eggs in IVF has been in practice for many years and is a standard part of IVF therapy. In one large trial by Cabo et al. in 2010, found no significant differences in the pregnancy rates per transfer between vitrified frozen and fresh eggs (55.4% vs. 55.6%.)

Are there risks to the baby born from frozen eggs?

The short-term data on children born from frozen eggs show no increased risk of congenital anomalies when compared to the general population. However, there is limited long-term data on children born from frozen eggs. Currently, the available data show no increased safety issues in children born from forzen eggs compared to children born conventionally.

Reference

Glenn LS. Cryopreservation of Oocytes. N Engl J Med 2015; 373:1755-1760

Parmegiani L, Garello C, Granella F, Guidetti D, Bernardi S, Cognigni GE, et al. Long-term cryostorage does not adversely affect the outcome of oocyte thawing cycles. Reprod Biomed Online. 2009;19:374–9.

Urquiza MF, Carretero I, Cano Carabajal PR, et al. Successful live birth from oocyte after more than 14 years of cryopreservation. J Assist Reprod Genet. 2014;31(11): 1553.

Mature oocyte cryopreservation: a guideline. Practice Committees of American Society for Reproductive Medicine, Society for Assisted Reproductive Technology. Fertil Steril. 2013;99(1):37–43.

Cobo A, Meseguer M, Remohi J, Pellicer A. Use of cryo-banked oocytes in an ovum donation programme: a prospective, randomized, controlled, clinical trial. Hum Reprod. 2010;25:2239–46.

Noyes N, Porcu E, Borini A. Over 900 oocyte cryopreservation babies born with no apparent increase in congenital anomalies. Reprod Biomed Online. 2009;18:769–76.

The difference between PGD and PGS

IVF

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.

How many eggs are needed to be retrieved for IVF?

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.

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.

What is IVF?

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?

Uncategorized

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.