Freeze Eggs to be Free – Oocyte Cryopreservation is More Common than You Think.

Women’s fertility decreases with advancing age. This is the main reason why women seek to freeze eggs to preserve their fertility.

More specifically, women’s oocytes/follicles diminish in quality and quantity, resulting in increasing difficulty to conceive, a higher chance of delivering a chromosomally abnormal child, and most women start to be sterile around the age of 41 [1].  The decline wouldn’t be relevant or tangible to one until difficulties are encountered when attempting for pregnancy.

It should be made widely aware of the fact that there is a sharp drop in chance of pregnancy between women of age 20-24 at 86% to 35-39 at 52% [2] [3], and generally, most women are naturally infertile in the 40s [1].

Aging does not impact the uterus the degree, urgency, and restrictiveness it does for ovarian reserve and quality, women can still conceive at a later age with an implanted embryo (a fertilized oocyte with sperm) through in vitro fertilization (IVF); that being said, the success rate of live birth via IVF also decreases as the woman’s age depending on the youthfulness of the eggs/oocytes, the number of eggs for the cycles, and woman’s age at the time of the implantation [4].

WHAT YOU NEED TO KNOW TO FREEZE EGGS?

In Vitro Fertilization (IVF) and Cryopreservation

In-vitro Fertilization (IVF) is a type of assisted reproductive technology used for infertility treatment.

It is a process of controlled fertilization where an egg is combined with sperm outside the body (hence got the name In-Vitro), often in a test tube or petri dish performed inside a laboratory.  The fertilized egg (zygote) undergoes embryo culture for 2-6 days and is then transferred to the same or another women’s uterus attempting to establish a successful pregnancy [5].In vitro fertilization can overcome most causes of male and female infertility.

There are 3 essential components of an IVF process:

• Induction of ovulation – within 14 days from the date of menstruation,
• Fertilization of an oocyte, development of embryos – 2-6 days after receiving the sperm
• Implantation, transferring the embryo to a uterus – Implantation day, then observation within a trimester. It is usually done after 3-5 days of fertilization.

For more information on IVF, Mayo Clinic provides a good overview here https://www.mayoclinic.org/tests-procedures/in-vitro-fertilization/about/pac-20384716.

Oocyte cryopreservation or egg-freezing accounts for the first phase of IVF as induction of ovulation which involves:

• Stimulating the ovaries with hormones to produce multiple eggs from maturing the follicles, as IVF requires multiple eggs.
• Retrieving the eggs from the ovaries under full-body anesthesia.
• Instead of fertilizing oocyte(s), the eggs are preserved below -80 or -196 degrees via flash-freezing vitrification[6].
• The frozen eggs are used in the fertilization and development of embryos and implantation for bearing a child during a cycle of IVF later.

Since frozen embryos result in just as many live births in IVF.  

And there is a growing trend for late motherhood, many women resort to oocytes cryopreservation / egg-freezing to preserve the quality of eggs at the state [8].

Oocyte cryopreservation for IVF is an insurance; not a solution to a late motherhood.

43% was the success rate of having live birth via an IVF within the first 6 cycles of IVF based on a study on 113,873 women.  The result summary is shown further below [4].

Cycle of IVF	Live birth per cycle	Continued with next cycle
1st cycle of IVF	29.1%	39.9%
2nd cycle of IVF	24%	36.3%
3rd cycle of IVF	20%	33.7%
4th cycle of IVF	18.6%	34.1%
5th cycle of IVF	16.3%	36.2%
6th cycle of IVF	14.8%	37.7%

Alt tag: Number of women having live birth, not having a live birth but continuing in vitro fertilization (IVF), or not having a live birth and not continuing IVF (during follow-up) over six complete cycles of IVF

Younger women have a better success rate to yield live birth through IVF.  In the same study, the success rate of live birth was 47% in the 1^st cycle of IVF and 94% within 6 complete cycles for women aged 30 compared to 19% and 57% for women of 40 years old.

Freeze Eggs to Increase the Chance of Live Birth Later

With woman’s increasing age, the odds of a live birth over six complete cycles decreased.  The chances of a live birth declined after age 30 and decreased linearly with increasing duration of infertility.  Increasing egg numbers improved the chance of live birth considerably until 13 eggs; in short, 15 eggs are often concluded as a good number for retrieval to guarantee pregnancy [4].

As concluded in a study on 400,135 IVF treatment cycles, there was a strong association between the youthfulness of the eggs, the number of eggs, and the live birth rate.  Live birth rate rose with an increasing number of eggs up to around 15, plateaued between 15 and 20 eggs [9].

Retrieval Age Group	Live birth rate For 15 eggs retrieved
18-34	40%
35-37	36%
38-39	27%
40 years and over	16%

Alt tag: Live birth rate decreases as the age group increases given 15 eggs retrieved in the age group.

Depending on each individual and age, one retrieval operation of oocytes can result in 0-3 (low responder), 10-15 (normal), more than 15 (high responder).  It is common to require several retrievals to attain 15 eggs.  The higher the number of oocytes retrieved, the higher the number of euploid embryos (of a normal chromosome) is possible.  Increasing the oocyte yield from a single stimulation cycle is recommended while ensuring the chance of ovarian hyperstimulation syndrome is low.  To produce 1 to 2 euploid embryos, 5-14 oocytes would be required at 34, while 10-24 oocytes would be required at age 38 [10].

Younger Male Partner Increases the Chance of Fertilization

The biological clock doesn’t just apply to women.  Men’s fertility also declines as time flies.

Men’s semen parameters begin a steady decline as early as 35, and DNA damage of sperm can start from the age of 40 [11].  It is thus not surprising that a recent study revealed that pregnancy is also affected by the father’s age [12]:

• Age of the sperm donor/father
  • 20% decrease in successful pregnancy from men of age under 30 to 40-42.
  • For female partners under 30, the rate of yielding live birth decreased as the male partner ages: male partners with age 30-35 at 73% and with age 40-42 at 46%[12].
• Age of the female carrier
  • 46% decrease in successful pregnancy from women of age under 30 to 40-42.

Fortunately, Intracytoplasmic sperm injection (ICSI), an IVF procedure in which a single sperm cell is injected directly into the cytoplasm of an egg, is recommended as an alternative to a normal IVF if the challenge of fertilization is due to low sperm count and poor motility of sperms.  There is also a 24% increased advantage of live birth that ICSI is over IVF [4] [13].

Preimplantation Screening

At least 50% of human embryos are abnormal, which increases to 80% in women 40 years or older; selecting normal embryos for transfer would improve pregnancy results [14] [15].

• A study of using preimplantation screening test over 451 blastocysts amongst 120 women of 40-43 years old revealed that:
  • 4% are of euploid / normal,
  • 3% aneuploid of abnormal chromosome profile,
  • 2% were either chaotic or had no diagnosis.

To increase the chance of live birth and lower the chance of pregnancy loss and frustrations of failed cycles, it is possible to perform Preimplantation Genetic Diagnosis (PGD), analyzing the genetic and chromosomes of embryos before implantation in the uterus.

The same study showed that the live birth success rate is 51% for embryos gone through preimplantation screening, much higher than embryos without being screened 22.7% (including multiple gestations) [15]:

Cycle of IVF	Fresh Embryos without tests	Frozen Embryos with tests
Clinical Pregnancy /Transfer	36.6% (126/344)	55% (27/49)
Pregnancy Loss	38.1% (48/126)	10.7% (3/27)
Multiple Gestations	26.2% (33/126)	3.7% (1/27)
Live Birth / Transfer	22.7% (78/344)	51% (24/49)

Benefits of using PGD [15]:

• Increased chance of live birth
• Decreased chance of pregnancy loss, chromosomally abnormal pregnancies
• Avoidance of multiple gestations

In addition, it avoids the time delay from a miscarriage and the psychological effect of failed IVF cycle.

Complications of IVF:

IVF does have its own complications as any other medical treatment. They are:

1. Multiple pregnancies
2. Low birth weight and premature birth
3. Ectopic pregnancies
4. Ovarian Hyperstimulation Syndrome (ovaries might become swollen and painful).
5. Egg retrieval-related complications (infection, stress, anesthesia, etc.).

Freezing Eggs Does Not Cause Early Menopause

A research carried out in the United Kingdom confirmed that amongst the 199 respondents who had gone through at least one IVF in the ’80s using stronger stimulating drugs had their menopause around the same time as their mother.  The same article states that by the same logic, the prevention of ovulation through contraceptive pills does not delay menopause [16].

Points to Consider When Choosing Your Fertility Clinic

Points to take into account when choosing the facility to freeze your eggs:

• The number of single embryo transfers (eSET) performed versus double embryo transfers (2BET)?
  • This can indicate if the clinic has the best practice and has the latest and greatest equipment.
• Does the clinic possess the required reproductive certification in the country?
• Does it allow a non-married woman to freeze egg?
• Does it allow a non-married couple to do IVF?
• Can the eggs be transported to other facilities or countries?
• Is vitrification the technology (the latest technology) used for egg-freezing[17]?
• What is the longest preservation duration?
• What hormone injections are available?
• Does the clinic furnish preimplantation genetic diagnosis?
• What are the costs for:
  • Oocyte cryopreservation
  • In vitro fertilization
  • Intracytoplasmic sperm injection (ICSI) / Intracytoplasmic morphologically selected sperm injection (IMSI)
  • Preimplantation genetic diagnosis

With the increasing trend of delaying childbearing, it is great news that women can freeze eggs to assure the possibility of delivering a child even later through IVF.  Bearing in mind that there are also multiple factors affecting the success rate of IVF, the age and quality of eggs, number of preserved eggs, and sperm quality, a woman can free her mind, even just for a little while, by choosing to freeze eggs, as young as the age of 18 preserving the egg’s quality to feel free at a later stage in life when she is ready to have a family [1].

We can’t fight time.  We can, however, prime with time and prepare ourselves at the present moment for a better future.

Wonder if there is a good or bad time to get pregnant? Check out this researched article.

---

References:

[1]   E. Velde e P. Pearson, «The variability of female reproductive aging,» 2002. [Online]. Available: https://pdfs.semanticscholar.org/9b38/719e86481ed960dd84bc1d2456c9aa0b82e5.pdf.

[2]   D. Dunson, B. Colombo e D. Baird, «Changes with age in the level and duration of fertility in the menstrual cycle,» 1 May 2002. [Online]. Available: https://academic.oup.com/humrep/article/17/5/1399/845579#14634656.

[3]   EUROPEAN SOCIETY OF HUMAN REPRODUCTION AND EMBRYOLOGY (ESHRE), «PERSONALISED MEDICINE: Individual Choices in Reproductive Health,» 6 October 2010. [Online].

[4]   D. McLernon, E. Velde e S. Bhattacharya, «Predicting the chances of a live birth after one or more complete cycles of in vitro fertilization: a population-based study of linked cycle data from 113 873 women,» 19 October 2016. [Online]. Available: http://www.bmj.com/content/355/bmj.i5735.

[5]   «In vitro fertilization,» [Online]. Available: https://en.wikipedia.org/wiki/In_vitro_fertilisation.

[6]   «Cryopreservation,» [Online]. Available: https://en.wikipedia.org/wiki/Cryopreservation#cite_note-1.

[7]   The University of Adelaide, «Frozen embryos result in just as many live births in IVF,» 9 January 2018. [Online]. Available: https://www.alphagalileo.org/ViewItem.aspx?ItemId=182468&CultureCode=en.

[8]   L. Donnelly, «Number of women freezing their eggs triples in just five years,» 23 March 2016. [Online]. Available: http://www.telegraph.co.uk/news/2016/03/23/number-of-women-freezing-their-eggs-triples-in-just-five-years/.

[9]   S. Sunkara, V. Rittenberg, N. Raine-Fenning, S. Bhattacharya, J. Zamora e A. Coomarasamy, «Association between the number of eggs and live birth in IVF treatment: an analysis of 400 135 treatment cycles,» 1 July 2011. [Online]. Available: https://academic.oup.com/humrep/article/26/7/1768/2913935.

[10] C. Venetis, «The more eggs, the better in IVF?,» 3 July 2017. [Online]. Available: https://www.eshre.eu/Annual-Meeting/Geneva-2017/ESHRE-2017-Press-releases/Venetis.aspx.

[11] R. Sharma, K. Biedenharn, J. Fedor e A. Agarwal, «Lifestyle factors and reproductive health: taking control of your fertility,» 16 July 2013. [Online]. Available: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3717046/.

[12] L. Dodge, «Delivery rates in IVF are affected by the age of the male partner,» 3 July 2017. [Online]. Available: https://www.eshre.eu/Annual-Meeting/Geneva-2017/ESHRE-2017-Press-releases/Dodge.aspx.

[13] B. Ola, M. Afnan, K. Sharif e S. Papaioannou, «Should ICSI be the treatment of choice for all cases of in-vitro conception?: Considerations of fertilization and embryo development, cost-effectiveness and safety,» 1 December 2001. [Online]. Available: https://academic.oup.com/humrep/article/16/12/2485/2919148#66910992.

[14] S. Munne, «Preimplantation Genetic Diagnosis for Aneuploidy and Translocations Using Array Comparative Genomic Hybridization,» September 2012. [Online]. Available: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3426780/.

[15] H.-L. Lee, D. McCulloh, B. Hodes-Wertz, A. Adler, C. McCaffrey e J. Grifo, «In vitro fertilization with preimplantation genetic screening improves implantation and live birth in women age 40 through 43,» 13 January 2015. [Online]. Available: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4363234/.

[16] «’No early menopause’ through IVF,» 2 May 2008. [Online]. Available: http://news.bbc.co.uk/2/hi/health/7373711.stm.

[17] C. Argyle, J. Harper e M. Davies, «Oocyte cryopreservation: where are we now?» 1 June 2016. [Online]. Available: https://academic.oup.com/humupd/article/22/4/440/2573626.