Author: Sara Gómez García “Gene expression in the embryo can be modulated by the uterus conditions or pregnant woman lifestyle” A couple seeking assisted reproduction treatment can choose either to use their own oocytes (eggs) or those from a third party (donor). In the latter case, oocytes will be inseminated with the partner’s semen or donor semen. INDICATIONS TO USE DONATED OOCYTES
At birth, the number of oocytes of a baby girl is limited, and progressively reduced over the course of her life. Broadly speaking, oocyte quality decreases with age, which increases the number of miscarriages and the number of children born with some kind of genetic abnormality (2, 3) (Fig.1). When the patient cannot count on her own oocytes, one of the most suitable options may be looking for a donor. WHO CAN BECOME AN EGG DONOR? An egg donor is a woman of legal age who has decided to give her eggs away for other women. Donors can be anonymous or non-anonymous, depending on what laws dictate in a specific country:
Egg donors must pass physical, genetic and psychological tests before even being able to commence the process. The assisted reproduction guidelines, stated by a variety of professional bodies, recommend different tests to evaluate the health status of oocyte donors (Table 1) (4, 5, 6, 7): WHERE IS LEGAL TO PERFORM AN EGG DONATION TREATMENT IN EUROPE? Even though egg donation is an procedure in expansion, it is not yet legal everywhere. In addition, treatments use anonymous and/or non-anonymous donors, as specified by the local legislation of each European country (Table 2). HOW COMMON IS IT TO USE DONOR EGGS? The first egg donation was performed thirty-five years ago (8). It is progressively becoming more common to use egg donors due to changes in lifestyle, with couples now waiting longer to have their first child. In 2013, 39,000 egg donation treatments were made in Europe out of a total of 500,000 IVF cycles, which corresponds to 7.8% of overall cycles. Furthermore, 50% of all them were performed in Spain (3). In 2015, 14,655 egg donation procedures were performed in Spain alone, which represents about 20% of all human assisted reproduction cycles in the country (9). In addition, data from 2014 showed 8.5% of all treatments in Spain were performed to foreign patients, 66% of them actually corresponding to egg donation procedures (3). It is possible that Spain carries out most of the donor oocyte cycles across Europe due to a combination of factors: less restrictive legislation, higher quality of techniques and excellent clinical outcomes. IS THIS PROCEDURE EFFECTIVE? Pregnancy rates with donor oocytes are higher than those achieved using the patient’s own oocytes in the different age ranges. This is likely due to the younger age of donors and the fact that uterine age does not affect results (Table 3). WILL MY CHILDREN SHOW ANY PHYSICAL RESEMBLANCE TO ME? The oocyte is fertilized by a sperm to form the embryo. Its DNA is, therefore, composed of oocyte DNA and sperm DNA. This mixture of DNA (genes) determines the physical characteristics of the embryo. However, there is another factor known as epigenetics that could modify such features. Epigenetics are changes in gene expression without changing the DNA sequence, which can be influenced by environmental conditions, age and a variety of factors. Regarding gene expression in the embryo, it can be influenced by the uterus conditions or lifestyle of the pregnant woman (diet, stress, drugs, toxins, hormones...). Also, not only the first generation (woman) is affected in terms of gene expression at the epigenetic level, but also the second and third generation may be affected, as well. Even the fourth generation could inherit an epigenetic effect despite not being directly exposed (Fig.2) (10). An example of these epigenetic changes is illustrated by a study performed in mice, in which the author showed that modulating the diet may modify coat color. Even though the investigated yellow and brown mice were genetically identical, the diet of the mother likely produced brown mice under a yellow genetic background (changes in gene expression) (11). In humans, studies have shown that adherence to a Mediterranean diet during pregnancy can have a protective effect against the development of metabolic diseases in the offspring (12, 13). Other research teams have investigated the effect of maternal cigarette smoking on children. This has been correlated to low birth weight, asthma, obesity, altered neurobehavior and cancer (14, 15). In conclusion, an ongoing communication is performed between mother and child (embryo) that could modulate gene expression in the embryo. Nevertheless, new research is necessary to fully understand this process. TAKE-HOME MESSAGE Egg donors can be anonymous and/or non-anonymous, and it is regulated by different legislations in different countries. Egg donation is becoming a more common process, pushed forward by the high pregnancy rates obtained in several age ranges without effects related to uterus age. Interestingly and as mentioned above, despite not being the genetic mother, gene expression in the embryo can be modulated by the uterine conditions or pregnant woman lifestyle. And remember... “Being a mother is an attitude, not a biological relation” Robert A. Heinlein REFERENCES
1. Broekmans F.J., Soules M. R., Fauser B. C. Clinical and endocrinological aspects of ovarian ageing. Endocrine Reviews [Internet] August 2009.[cited 2018 Jun 27] 30(5):465–493. 2. MANIFIESTO DE LA SEF SOBRE LA DONACIÓN DE GAMETOS EN ESPAÑA [Internet] Sociedad Española de Fertilidad. n.d. [cited 2018 Jul 25]. Available from: https://goo.gl/KZ6ZD9. 3. Egg donation fact sheets 3 [Internet] European Society of Human Reproduction and Embryology. January 2017 [cited 2018 Jul 25]. Available from: https://goo.gl/T86TLR. 4. Association of Biomedical Andrologists, Association of Clinical Embryologists, British Andrology Society, British Fertility Society, Royal College of Obstetricians and Gynaecologists. UK guidelines for the medical and laboratory screening of sperm, egg and embryo donors (2008). Hum Fertil (Camb). 2008 Dec;11(4):201–10. 5. Weinig JRM, Hernández JH. Estudio y tratamiento de la pareja estéril: Recomendaciones de la Sociedad Española de Fertilidad, con la colaboración de la Asociación Española para el Estudio de la Biología de la Reproducción, de la Asociación Española de Andrología y de la Sociedad Española de Contracepción [Internet]. Adalia farma; 2007 [cited 2018 Jul 25]. Available from: https://dialnet.unirioja.es/servlet/libro?codigo=562165. 6. Barratt C, Englert Y, Gottlieb C, Jouannet P. Gamete donation guidelines. The Corsendonk consensus document for the European Union. Hum Reprod [Internet]. 1998 Feb 1 [cited 2018 Jul 25];13(2):500–1. Available from: https://academic.oup.com/humrep/article/13/2/500/876942. 7. 2008 Guidelines for gamete and embryo donation: a Practice Committee report. Fertility and Sterility [Internet]. 2008 Nov 1 [cited 2018 Jul 5];90(5):S30–44. Available from: https://www.fertstert.org/article/S0015-0282(08)03714-X/fulltext. 8. Trounson A, Leeton J, Besanko M, Wood C, Conti A. Pregnancy established in an infertile patient after transfer of a donated embryo fertilised in vitro. Br Med J (Clin Res Ed) [Internet]. 1983 Mar 12 [cited 2018 Jul 5];286(6368):835–8. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1547212/. 9. Sociedad Española de Fertilidad [Internet] Registro Nacional de Actividad 2015: Informe estadístico de Técnicas de Reproducción Asistida 2015 [cited 2018 Jul 25]. Available from: https://goo.gl/ZB8EhA. 10. Genetic Science Learning Center (2013, July 15) [Internet]. August 21, 2018. Epigenetics & Inheritance [cited 2018 Jul 5]. Available from: http://learn.genetics.utah.edu/content/epigenetics/inheritance/. 11. Dolinoy DC. The agouti mouse model: an epigenetic biosensor for nutritional and environmental alterations on the fetal epigenome. Nutr Rev [Internet]. 2008 Aug [cited 2018 Aug 22];66(Suppl 1):S7-11. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2822875/. 12. Lorite Mingot D, Gesteiro E, Bastida S, Sánchez-Muniz FJ. Epigenetic effects of the pregnancy Mediterranean diet adherence on the offspring metabolic syndrome markers. Journal of Physiology and Biochemistry [Internet]. 2017 [cited 2018 Aug 26];73(4):495–510. Available from: http://link.springer.com/10.1007/s13105-017-0592-y. 13. Geraghty AA, Lindsay KL, Alberdi G, McAuliffe FM, Gibney ER. Nutrition During Pregnancy Impacts Offspring’s Epigenetic Status—Evidence from Human and Animal Studies. Nutr Metab Insights [Internet]. 2016 Feb 16 [cited 2018 Aug 26];8(Suppl 1):41–7. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4758803/. 14. Armstrong DA, Green BB, Blair BA, Guerin DJ, Litzky JF, Chavan NR, et al. Maternal smoking during pregnancy is associated with mitochondrial DNA methylation. Environ Epigenet [Internet]. 2016 Aug 1 [cited 2018 Aug 26];2(3). Available from: https://academic.oup.com/eep/article/2/3/dvw020/2415103. 15. Joubert BR, Håberg SE, Bell DA, Nilsen RM, Vollset SE, Midttun Ø, et al. Maternal smoking and DNA methylation in newborns: In utero effect or epigenetic inheritance? Cancer Epidemiol Biomarkers Prev [Internet]. 2014 Jun [cited 2018 Aug 26];23(6):1007–17. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4140220/.
2 Comments
Georgi Doychev
8/28/2018 15:06:11
Can you please add Bulgaria and Macedonia to table 2: It is legal with anonymous egg donors.
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Sara Gómez
8/28/2018 21:08:17
Dear Mr. Doychev,
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