Egg Freezing at Age Seven
“Fertility preservation should be offered to girls at risk for premature ovarian failure before the critical point of no return.”
This episode discusses a landmark report about the youngest girl who has ever undergone egg freezing, a process formally known as “oocyte cryopreservation.” This study was just published in May in the reproductive journal Fertility and Sterility.
This young girl has Turner Syndrome (45,X[37]/47,XXX[15] mosaicism).
About Turner Syndrome
Affects ~ 1 in 2500 females
Chromosomal abnormality where, instead of having two X chromosomes, females with Turner Syndrome are missing all or some portion of an X chromosome
Results from a random biological error when the baby is in utero (vs. genetic inheritance)
Rare for those affected to conceive naturally
Back to the Case
The parents of an almost seven-year -old Israeli girl sought fertility counseling to learn about their daughter’s future options. Lab results and an ultrasound revealed that the daughter had a low but existing ovarian reserve [anti-Muellerian hormone (AMH) 1.13 ng/mL, antral follicle count (AFC) of five follicles].
After speaking with a fertility expert, a pediatric endocrinologist, and a mental health specialist at Tel Aviv University, the parents learned they had three options. The fertility options were:
Egg donation - the most successful method for people with Turner Syndrome to have children.
Freezing ovarian tissue - invasive and experimental but may give pre-pubertal girls a chance to biologically conceive.
Freezing eggs (cryopreserving oocytes) - also invasive and experimental, especially in a pre-pubertal girl. Thus far, however, tissue preservation has been less successful than egg freezing at preserving fertility.
The parents went with option #3. Because this was so novel and experimental to try in such a young girl, an ethics committee at Tel Aviv University reviewed this case and approved it after hearing insight from fertility specialists.
As for this young girl, she “received counseling in a developmentally appropriate manner. Her main concern was whether the procedure would be painful and whether she would be able to participate in her jazz dance classes.”
Stimulation and Retrieval
Cycle 1
The table below details the medications used for eight days of ovarian stimulation to grow the oocytes as well the gonadotropin-releasing hormone agonist used once to trigger the release of oocytes.
After anesthesia and prophylactic antibiotics, the oocyte retrieval procedure was conducted intra-abdominally. Unfortunately, the stimulated follicles were empty, and no oocytes were retrieved.
Cycle 2 - 40 days later
The medications used in Cycle 1 were slightly increased, as per the table below. The girl was given a different “trigger shot” to complete oocyte maturation - instead of triptorelin, she received one dose of human chorionic gonadotropin (hCG).
The retrieval under anesthesia was the same as Cycle 1 except this time, six oocytes were retrieved, and all were of sufficient maturity to be cryogenically frozen for a future opportunity to conceive.
rFSH = recombinant Follicle Stimulating Hormone; rLH = recombinant Luteinizing Hormone; hCG = human chorionic gonadotropin
Conclusions
The authors of this study emphasized that trying to preserve eggs in young girls should only occur in exceptional circumstances. They noted that cancer and chemotherapy produce different hormonal circumstances than Turner Syndrome, so this practice of retrieving eggs before puberty should not be universally adopted. Having said that, the ability to freeze eggs in pre-pubertal girls is incredibly encouraging! ! It will be interesting to see how this practice is repeated and honed in the future to protect fertility.
Resources
Azem F, Brener A, Malinger G, et al. Bypassing physiological puberty, a novel procedure of oocyte cryopreservation at age 7: a case report and review of the literature [published online ahead of print, 2020 May 5]. Fertil Steril. 2020;S0015-0282(20)30284-3. doi:10.1016/j.fertnstert.2020.03.009.
Doğer E, Y Çakıroğlu, Ceylan Y, Ulak E, Özdamar O, Çalışkan E. Reproductive and obstetric outcomes in mosaic Turner’s syndrome: a cross-sectional study and review of the literature. Reprod Biol Endocrinol 2015;13:59. doi:10.1186/s12958-015-0055-7.
Folsom LJ, Fuqua JS. Reproductive Issues in Women with Turner Syndrome. Endocrinol Metab Clin North Am. 2015;44(4):723‐737. doi:10.1016/j.ecl.2015.07.004.
Nahata L, Woodruff TK, Quinn GP, et al. Ovarian tissue cryopreservation as standard of care: what does this mean for pediatric populations?. J Assist Reprod Genet (2020). doi: 10.1007/s10815-020-01794-7.
Onalan G, Yilmaz Z, Durak T, Sahin FI, Zeyneloglu HB. Successful pregnancy with preimplantation genetic diagnosis in a woman with mosaic Turner syndrome. Fertil Steril. 2011;95(5):1788–e1-3. DOI: 10.1016/j.fertnstert.2010.12.055.
Sun, T. Transvaginal Vs. Transabdominal Ultrasound in Oocyte Retrieval. https://www.volusonclub.net/empowered-womens-health/transvaginal-vs-transabdominal-ultrasound-in-oocyte-retrieval/ Published 2019. Accessed June 2, 2020.
Turner Syndrome Clinic. The basics about mosaic Turner Syndrome. https://www.massgeneral.org/children/turner-syndrome/the-basics-about-mosaic-turner-syndrome. Published 2019. Accessed June 2, 2020.
