Nigerian Medical Journal

REVIEW ARTICLE
Year
: 2019  |  Volume : 60  |  Issue : 3  |  Page : 99--105

Preimplantation genetic testing for breast cancer


Eunice I Oribamise1, Oladapo A Ashiru2, Ebele C Iloabachie2, Jumoke G Osumah2, Oladimeji O Moruf2,  
1 Medical ART Center, Institute of Reproductive Medicine, Ikeja, Lagos State; Department of Anatomy, Babcock University, Ilishan-Remo, Ogun State, Nigeria
2 Medical ART Center, Institute of Reproductive Medicine, Ikeja, Lagos State, Nigeria

Correspondence Address:
Oladapo A Ashiru
Medical Assisted Reproductive Technology Center, Ikeja, Lagos State
Nigeria

Abstract

Breast cancer (BC), a malignant tumor characterized mainly by a lump in the breast and a change in breast shape, has plagued many women of childbearing age in Nigeria today. This has thus propelled many to find both prophylactic and curative agents to combat BC in affected persons. This article extensively reviews a method of preventing BC in the offspring of affected parents, known as preimplantation genetic testing (PGT) – an assisted reproductive technique that selects genetically unaffected embryo(s) to be transferred to the uterus of a mother upon in vitro fertilization and standard genetic analysis. The present study also seeks to present the techniques involved in PGT that have been reported to prevent the inheritance of BC, its benefits and risks, related case studies in Africa and other continents, and ethical issues surrounding the application of assisted reproduction for BC testing. To achieve these, a thorough search was conducted in reputable scientific journals of reproduction and cancer, and expert knowledge was consulted with regard to these aspects of health and reproduction. Upon reviewing this very important subject, it was confirmed that the beneficial role of assisted reproduction in the field of science and the homes of many cannot be overestimated. This review of the role of PGT in BC prevention will enlighten the understanding of many – creating awareness that with PGT, BC-affected women can have not only children, but also healthy and genetically unaffected children.



How to cite this article:
Oribamise EI, Ashiru OA, Iloabachie EC, Osumah JG, Moruf OO. Preimplantation genetic testing for breast cancer.Niger Med J 2019;60:99-105


How to cite this URL:
Oribamise EI, Ashiru OA, Iloabachie EC, Osumah JG, Moruf OO. Preimplantation genetic testing for breast cancer. Niger Med J [serial online] 2019 [cited 2019 Sep 17 ];60:99-105
Available from: http://www.nigeriamedj.com/text.asp?2019/60/3/99/264954


Full Text

 Introduction



It is of little or no surprise that breast cancer (BC) has led to the death of many women around the globe.[1],[2] As a malignancy of the breast tissue, BC has become a plague common in females of reproductive age in Nigeria and Africa as a whole.[3],[4] Another crisis of BC is its high inheriting capability of the BCRA1 and BCRA2 gene mutation that leads to cancer[5] such that in addition to facing a lifetime risk of cancer, BRCA mutation carriers also need to cope with a 50% chance of transmitting the mutation to their children.[6] The gene mutation carriers, either male[7] or female, thus have a desire that their offspring are genetically normal, not carriers of the gene mutation. In the quest to fulfill this desire, several reproductive options have developed over time, two of which have proved worthy and can lead to the testing and consequent avoidance of the mutation in offspring, namely prenatal diagnosis (PND) and preimplantation genetic testing (PGT). While PND (including chorionic villus sampling and amniocentesis) involves the testing of the fetus for the presence of the BRCA1/2 mutation during pregnancy[8],[9] where unfavorable results may lead to the parents having to make the difficult decision of pregnancy termination or bearing a child who has the tendency to develop breast malignancy, PGT offers a chance to select genetically unaffected embryos even before implantation.[10],[11] It is important to note that PGT is a replacement of preimplantation genetic diagnosisand preimplantation genetic screening.[12] Assisted reproductive technologies (ARTs) have indeed offered a better alternative to many BRCA1/2 mutation-affected parents who, beyond the choices of gamete donation and adoption, seek to have their own biological children. With the embryos “created” and tested for in vitro, the major benefit of PGT for BC is that only the unaffected embryos are implanted to try to conceive, nullifying any chances of the mutation being present in the offspring and subsequent generations even in a family with a past medical history of BC. With advances in technology, assisted reproduction has only seen tremendous progression, leaving various historical landmarks that create platforms for more hope-giving techniques; some of these events include:

1978: Birth of the firstin vitro fertilization (IVF) baby by Steptoe and Edwards[13],[14]1989:First applications for PGT (in testing monogenic disorders and sex-linked disorders using polymerase chain reaction [PCR] for the Y chromosome from a blastomere) by works done by Handyside et al.[15],[16]1990:First successful PGT baby born for X-linked disorder[17]1990: Discovery of BCRA mutation in BC by Hall and team[18]1999–2001: PGT for late-onset common disorders with genetic predisposition[19],[20]2008: The first report of a baby born after PGT for the BCRA mutation[21]2015:First PGT in Nigeria.[22]

 Methodology of Information Gathering



During this review, the main search engine employed for the gathering of information was Google Scholar[23],[24] which is known for its vastness in abstracts, papers, patents, theses, and dissertations. Citations of related studies were further searched for, and an in-depth review was carried out correspondingly. Furthermore, experts who have contributed to both fields of interest (i.e., assisted reproduction and BC) were consulted through ResearchGate for further expertise so as to arrive at this robust and well-informative review. Magazine articles and television documentaries also served as good information sources. MEDLINE and PubMed indexes[25],[26] were also used as search engines in this review.

 Nigeria and Preimplantation Genetic Testing for Breast Cancer



Although PGT is widely used in many other parts of the world, it is still a growing aspect of IVF in Nigeria. PGT has, in many localities, been made similar to the “designer baby” concept. Among other objectives, this article thus seeks to shed more light on the PGT technique as a beneficial one rather than a mere experimental one. In PGT, testing is carried out, and healthy embryos are chosen for the transfer and subsequent birth of a healthy child – thus, it is more diagnostic rather than therapeutic.

Nigeria is one of the developing countries, where PGT for BC may not yet be acceptable as a result of various factors which may include culture, religion, or individual beliefs. Below are some statistical statements of problem regarding BC that may influence the adoption of PGT by the medical community and the general public in Nigeria.

In 2008, it was projected by Boyle and Levin that 70% of all new cases of cancer in 2030 will be found in developing countries.[27]

Also, in 2008, Nigeria contributed 15% to the estimated 681,000 new cases of cancer that occurred in Africa.[28]

BC (50.8%) and cervical cancer (15.7%) were found to be most common in a study after an analysis of two population-based cancer registries in Nigeria: the Ibadan Population-Based Cancer Registry and the Abuja Population-Based Cancer Registry from 2009 to 2010.[29]

Furthermore, in 2010, the Estimates of Worldwide Burden of Cancer reported that some 100,000 new cases of cancer occur every year in Nigeria, with high case fatality ratio.[30]

Aside a list of such statistics, fertility clinics in Nigeria have reported their use of PGT to help diagnose BC and the consequent testimonies of healthy babies.[31]

PGT is also currently used for aneuploidy, sickle cell screening, and family balancing in Nigeria.

 Procedure of Preimplantation Genetic Testing for Breast Cancer



Upon gathering relevant information from reported studies, the following are the procedures of PGT in the testing of BC.

Pre-PGT checkup: The medical and genetic history of both partners are analyzed, a pedigree analysis is carried out, and physical observations including age and body mass index (BMI) are carried out for the female as some studies have associated obesity and increased age with reduced fertility and lower IVF success rates.[32] In addition, a 2008 study found that BMI on IVF success appeared age related,[33] where a high BMI was shown to have a pronounced negative influence on fertility, but this effect diminished as the patient's age increased. Gynecological, andrological, and oncological screening procedures (which were specially recommended by Derks-Smeets et al. in 2014[9]) are carried out including semen analysis to observe sperm morphology, motility, and count among other factors; female hormonal assessment of estrogen, luteinizing hormone, follicle-stimulating hormone, and anti-Mullerian hormone is carried out;[34],[35] and virology tests of both partners to ensure their suitability for IVF/intracytoplasmic sperm injection (ICSI) treatment are carried out.[36] ICSI is carried out to ensure that the “best” sperm is used to fertilize the oocyte and to avoid contamination of the zona pellucida with spermatozoa (i.e., DNA contamination from residual sperm adhering to the zona pellucida), which may affect the PGT analysis.[37]

Thereafter, oocyte maturation is triggered with recombinant choriogonadotropin-α, and retrieval is done about 36 h later.[38] The mature oocytes are then each fertilized by a single sperm of good morphology, and motility was identified for ICSI. The resulting embryos are then cultured for 3 (cleavage stage) or 5 days (blastocyst stage) depending on the best type of biopsy the clinic chooses.

The cleavage-stage biopsy [Figure 1] involves the removal of a single embryonic cell (blastomere), or two, at the 6–8 cells' stage, corresponding with the 3rd day of development.[39] Although removal of two blastomeres has been shown to result in a greater decline in live birth than a single-cell biopsy, there has been increased use of two-cell blastomere biopsy, it has been used by many centers globally.[40],[41] Prior to biopsy, the embryos are transferred to calcium-/magnesium-free media to facilitate blastomere removal,[39],[42] after which the zona pellucida is opened with laser, mechanical dissection, or exposure to acidic Tyrode's solution.[43] The blastomere is removed after the introduction of a biopsy pipette by aspiration or by extrusion of the cell with pressure on the outside of the zona. Furthermore, this day-3 biopsy allows 2–3 days for PGT analysis to be completed if a fresh embryo transfer is desired.[44]{Figure 1}

Trophectoderm biopsy involves the removal of 5–10 trophectoderm cells from blastocysts on day 5 or 6 after laser-assisted hatching on day 3,[45] which creates a 25–30-μm opening in the zona pellucida, allowing herniation of the trophectoderm cells through the zona as shown in [Figure 2].[45],[46]{Figure 2}

[Figure 3] shows the trophectoderm biopsy/blastocyst-stage biopsy. The cells are stretched out in a biopsy pipette and removed with a laser.[47],[48],[49] In comparison to the cleavage-stage biopsy, in this type of biopsy, more cells are collected for analysis, and it is believed to be less harmful to the embryos because trophectoderm cells are removed and cells from the inner cell mass are avoided.[48],[50]{Figure 3}

Although there is a third biopsy procedure, but does not apply to this study as it is only the polar body that testing is carried out on, no paternal analysis is carried out.[51]

After cells are biopsied, they are washed in preparation for the PCR procedure. Among the many other PGT techniques, PCR analysis has been reported in many of such BC-PGT cases,[52],[53],[54] of which some cases then reported the concomitant use of a comparative genomic hybridization or next-generation sequencing for further analysis.[55],[56] Upon analysis completion, the embryos are classified as affected (BRCA1/2 mutation present), unaffected (BRCA1/2 mutation absent), abnormal (abnormal genotype, e.g., haploidy or triploidy), or no testing (no test result or inconclusive BRCA1/2 status). Subsequently, one or two unaffected embryos are transferred into the uterus at day 4 or 5 postfertilization. The number of transferred embryos depends on embryo quality, female age, number of previous unsuccessful attempts, and the couples' preference for transferring only one embryo. Supernumerary unaffected embryos of sufficient quality are cryopreserved and are transferred in a subsequent cycle after thawing (defined as frozen-thawed embryo transfer).[57] Pregnancy rates are reported as positive human chorionic gonadotropin tests as well as clinical pregnancy rates. The clinical pregnancy rate is diagnosed according to the standard definition, i.e., a pregnancy diagnosed by transvaginal ultrasonographic visualization of one or more gestational sacs and appreciating any pregnancy abnormalities including ectopic pregnancies. Couples are given the option of prenatal testing (PNT) to confirm the PGT outcome. Follow-up of pregnancies and children is carried out;[58] all female BRCA1/2 carriers are contacted by telephone and inquired for their health status, including testing of BC because the last PGT treatment and prophylactic surgeries are performed in the meantime. Further testing is also encouraged, even up to postnatal testing of umbilical cord blood.

 Psychological Impact of Preimplantation Genetic Testing Toward Breast Cancer



Receiving a testing of BC or having a BRCA mutation is an anxiety-provoking event that can impact patients' psychosocial well-being. Because fertility preservation must be discussed as early as possible after a BC testing, women with a BRCA mutation face the additional burden of making future-oriented reproductive decisions in a short time frame while under significant stress.[59] Some centers and studies have even reported the measurement of psychological impact of cancer and/or carrying a BRCA1 or BRCA2 mutation and the implications for future childbearing using the Impact of Event Scale.[60] The thought that there is a whooping 50% chance of one's offspring may also be diagnosed with the mutation and pass through the same traumatizing experience is another associated psychological burden; this thus leads them to make the decision of applying assisted reproduction (also considered costly) which they otherwise will not have employed, especially for those without fertility problems. A study by Woodson et al. in 2014 with the aim of evaluating how BRCA genetic test result disclosure and patient characteristics influence attitudes toward PGT and future childbearing in counseling women with possible or identified BRCA mutations showed that 83% of the women said that PGT should be available to families with inherited cancer syndromes.[61] Similarly, another 2014 study, but with respect to PGT–PND comparison, was carried out to determine how couples with a BRCA1/2 mutation decide on PGT and PNT for hereditary BC and ovarian cancer (HBOC) syndrome, where a group of well-informed, reproductive-aged couples carrying a BRCA1/2 mutation were interviewed and their reproductive decisional motives and considerations were studied; it was then observed that none of the couples who opted for PGT or conception without testing found the use of PND with possible pregnancy termination acceptable.[62]

 Religious Bias



The attitude of the population of religious groups in several countries has a strong influence on the practice of assisted reproduction, PNT and PGT,[63] with abortion being of major worry in PND unlike the case of PGT where there is a preselection of embryos, and therefore abortion is avoided.[64] While the Roman Catholic Christian holds that the fetus has attained its status as a human being at conception, thus disapproving PGT,[65] the Jewish religion's view is that an unborn fetus is not considered a person until birth, but a part of the mother's body and not a separate being until it is delivered; in fact, they hold that prior to 40 days after conception, the fertilized egg – still an early zygote – has no status at all, it is not a person or “nefesh” (soul) and thus can be disposed of. The Islamic law may accept research on excess embryos resulting from IVF in order to increase their “ilm” (knowledge), and this may be possible in cases where it will be for the sake of the individual embryo. Researches conducted on preembryos should be limited to therapeutic research, and this includes genetic testing of a portion of the embryo, one blastomere, or its nucleus for a specific genetic defect. They view PGT as God-given knowledge in medical science to further help humans understand medical genetics. Research aimed at changing the inherited characteristics of preembryos is forbidden.[66] A study in Malaysia also reported that Christian scholars are very skeptical of the long-term use of PGT because of its possible effect on the value of humanity and the parent–child relationship.[67] Like Malaysia, Nigeria is a multireligious country, where the society places a high value on marital relationships and on the traditional concepts of family; more research should thus be carried out to see if the patronage of PGT for BC and other testing is based largely on religious views.

 Downsides to Preimplantation Genetic Testing



Patients and clinicians must recognize some barriers to PGT, particularly for women diagnosed with cancer. The high cost of IVF and PGT is often a burden, particularly when combined with the cost of cancer treatment.[68]

Other downsides may include procedural risks: Like all types of medical treatments and procedures, PGT treatment has its own risks and uncertainties which are discussed with the patients before any treatment is carried out. They are otherwise known as “procedural uncertainties.” Most of the risks involved in the PGT treatment are similar to those for the conventional IVF procedure, some of which include multiple pregnancies;[69] pelvic infections;[70] greater risk of premature delivery and delivery by cesarean section;[71] mechanical injury; and puncture of bowel, bladder, ureters, or blood vessels by the needle during egg retrieval. Some risks associated with the PGT-born babies may include premature birth, less weight than normally conceived babies at the same age,[71] risk of damage to embryos during biopsy,[72] hence the vast usage of blastocyst-stage biopsy for analysis, as this biopsy stage tends to leave the main embryonic cells unharmed; it is also important to note that those performing both the biopsy and the analysis must be highly technically-skilled.

 Ethics of the Preimplantation Genetic Testing Procedure for Breast Cancer



For the sake of proper understanding, moral and ethical considerations have been defined and differentiated in previous studies – moral considerations such as individual principles regarding a person's conduct and ideals, usually internal, and ethical considerations such as social and external rules of conduct regarding human actions. In 2003, the Ethics Task Force of the European Society of Human Reproduction and Embryology (ESHRE) approved the PGT use for late-onset and multifactorial diseases, including HBOC. The ESHRE Task Force for law and ethics stated that “PGT for late-onset diseases is acceptable, in spite of the still-existing uncertainties concerning therapy in the time gap between the birth of the child and the onset of the disease.” The task force also declared that “PGT can also be accepted in multi-factorial diseases like BRCA1/2 notwithstanding the uncertainties about the genetic predisposition and the epigenetic influence.”[73] This study and other opinion surveys have shown that most BRCA carriers consider PGT for HBOC as an acceptable reproductive option, although interestingly, only a minority of them would consider using PGT personally.[74],[75] In May 2006, the UK Human Fertilisation and Embryology Authority (HFEA) approved the use of PGT for lower penetrance and late-onset cancer susceptibility syndromes such as HBOC.[74] Among other considerations, it is important to note that ethical decisions on scientific procedures are usually made based on the opinions of the recipients of such procedure. For example, studies examining the opinions toward PGT among men and women with a BRCA mutation have shown that 13%–33% would want to pursue PGT if they were trying to conceive.[75] Even after the ESHRE decision on PGT for late-onset decision, studies are still carried out by Menon et al., Quinn et al., and Julian-Reynier et al.,[74],[76],[77] reporting the opinions of PGT for BRCA mutation.

The PGT procedure has created controversy since its inception, with the ethics centering on arguments over the moral status of the embryo. Because PGT may result in the destruction of embryos and fetuses, controversy has risen between those that contend that all human embryos and fetuses have the same moral status as live-born persons (hence, they are also entitled to rights including that of not to be killed)[78] and those that hold that embryos and fetuses lack any properties such as sentience or cognitive traits that determine moral standing and so can be destroyed at will and that they lack interests and other moral claims.[79] PGT for late-onset genetic cancers such as BRCA1 or BRCA2 holds specific questions concerning the time lapse of testing and severity of the disease, consequently improving the ability of genetic counselors and health-care providers and providing health-care professionals with the appropriate information and support during BRCA pre- and postcounseling.[61],[80]

Some of the controversial “ethical” issues that still remain in Nigeria are the transfer of multiple embryos in the quest to secure at least one fetus, thus leading to multiple births and, in some cases, risk to the life of the mother during childbirth. This, and other issues, thus led to the need of a regulating body in Nigeria. Even though a separate ethical body, such as the HFEA, is yet to be established in Nigeria, the practice of ART is currently being regulated by the guidelines of the Association for Fertility and Reproductive Health, a member society of the International Federation of Fertility Societies. Lagos State has also produced and launched the regulations and guidelines for ART practices including PGT.[81],[82] Many fertility clinics, though, have in-house ethical teams to self-regulate their practice, and some also use higher governing bodies, for example, medical ART center is guided by the regulations and guidelines of American Society for Reproductive Medicine and American Board of Bioanalysis. Even though the AFRH currently stands in the gap to reduce ART abuse, there is still a call – an advocacy to establish an ethical body to strictly regulate this practice. This will also, in turn, make patients more receptive to the concept of IVF, PGT, and ART as a whole.

 Conclusion



The medical community and the general public of both in the Nigeria and the world at large should have a deep understanding of the entire concept of PGT for early Breast Cancer diagnosis, as this will enable all to know the associated benefits, risks, etc., as reviewed in the present study.

Acknowledgment

The authors sincerely thank the Oribamise family, the staff of the Medical ART Center for technical help, and the members of staff of the Department of Anatomy at Babcock University for their never-ending support.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin 2005;55:74-108.
2Riihimäki M, Thomsen H, Brandt A, Sundquist J, Hemminki K. Death causes in breast cancer patients. Ann Oncol 2012;23:604-10.
3Amin SM, Ewunonu HA, Oguntebi E, Liman IM. Breast cancer mortality in a resource-poor country: A 10-year experience in a tertiary institution. Sahel Med J 2017;20:93-7.
4Ohanaka CE. Breast cancer in young Nigerian women. Niger J Surg Sci 2007;17:86-90.
5Chen S, Parmigiani G. Meta-analysis of BRCA1 and BRCA2 penetrance. J Clin Oncol 2007;25:1329-33.
6Famorca-Tran J, Roux G. The consequences of a BRCA mutation in women. J Adv Pract Oncol 2015;6:194-210.
7Mohamad HB, Apffelstaedt JP. Counseling for male BRCA mutation carriers: A review. Breast 2008;17:441-50.
8Lancaster JM, Wiseman RW, Berchuck A. An inevitable dilemma: Prenatal testing for mutations in the BRCA1 breast-ovarian cancer susceptibility gene. Obstet Gynecol 1996;87:306-9.
9Derks-Smeets IA, de Die-Smulders CE, Mackens S, van Golde R, Paulussen AD, Dreesen J, et al. Hereditary breast and ovarian cancer and reproduction: An observational study on the suitability of preimplantation genetic diagnosis for both asymptomatic carriers and breast cancer survivors. Breast Cancer Res Treat 2014;145:673-81.
10Ehrich K, Williams C, Farsides B, Sandall J, Scott R. Choosing embryos: Ethical complexity and relational autonomy in staff accounts of PGD. Sociol Health Illn 2007;29:1091-106.
11Cooper AR, Jungheim ES. Preimplantation genetic testing: Indications and controversies. Clin Lab Med 2010;30:519-31.
12Zegers-Hochschild F, Adamson GD, Dyer S, Racowsky C, de Mouzon J, Sokol R, et al. The international glossary on infertility and fertility care, 2017. Fertil Steril 2017;108:393-406.
13BBC. First 'Test Tube Baby' Born”. The Birth of the World'sFirst “Test Tube Baby” has Been Announced in Manchester (England). Louise Brown was Born Shortly before Midnight in Oldham and District General Hospital; 25 July, 1978. [Last retrieved on 2009 Jun 13].
14Steptoe PC, Edwards RG. Birth after the reimplantation of a human embryo. Lancet 1978;2:366.
15Franasiak J, Scott RT. Brief History of Preimplantation Genetic Testing and Preimplantation Genetic Screening. Virtual Academy of Genetics. Available from: https://ivf-worldwide.com/cogen/oep/pgt-pgs/ history-of-pgt-and-pgs.html. [Last accessed on 2018 Aug 23].
16Handyside AH, Kontogianni EH, Hardy K, Winston RM. Pregnancies from biopsied human preimplantation embryos sexed by Y-specific DNA amplification. Nature 1990;344:768-70.
17Handyside AH, Lesko JG, Tarín JJ, Winston RM, Hughes MR. Birth of a normal girl afterin vitro fertilization and preimplantation diagnostic testing for cystic fibrosis. N Engl J Med 1992;327:905-9.
18Hall JM, Lee MK, Newman B, Morrow JE, Anderson LA, Huey B, et al. Linkage of early-onset familial breast cancer to chromosome 17q21. Science 1990;250:1684-9.
19Available from: http://pgtis.org/history.html. [Last accessed on 2018 May 17].
20Verlinsky Y, Rechitsky S, Verlinsky O, Xu K, Schattman G, Masciangelo C, et al. Preimplantation diagnosis for p53 tumour suppressor gene mutations. Reprod Biomed Online 2001;2:102-5.
21Jasper MJ, Liebelt J, Hussey ND. Preimplantation genetic diagnosis for BRCA1 exon 13 duplication mutation using linked polymorphic markers resulting in a live birth. Prenat Diagn 2008;28:292-8.
22Available from: http://www.medicalartcenter.com/nigeria-records- first- birth-following-new-technology-in-ivf/. [Last accessed on 2018 May 17].
23Shultz M. Comparing test searches in PubMed and Google scholar. J Med Libr Assoc 2007;95:442-5.
24Haddaway NR, Collins AM, Coughlin D, Kirk S. The role of Google scholar in evidence reviews and its applicability to grey literature searching. PLoS One 2015;10:e0138237.
25Dunikowski LG. EMBASE and MEDLINE searches. Can Fam Physician 2005;51:1191.
26McKeever L, Nguyen V, Peterson SJ, Gomez-Perez S, Braunschweig C. Demystifying the search button: A comprehensive PubMed search strategy for performing an exhaustive literature review. JPEN J Parenter Enteral Nutr 2015;39:622-35.
27Boyle P, Levin B. World Cancer Report. Lyon, France: International Agency for Research on Cancer; 2008.
28Sylla BS, Wild CP. A million Africans a year dying from cancer by 2030: What can cancer research and control offer to the continent? Int J Cancer 2012;130:245-50.
29Jedy-Agba E, Curado MP, Ogunbiyi O, Oga E, Fabowale T, Igbinoba F, et al. Cancer incidence in Nigeria: A report from population-based cancer registries. Cancer Epidemiol 2012;36:e271-8.
30Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: Globocan 2008. Int J Cancer 2010;127:2893-917.
31Available from: https://www.vanguardngr.com/2017/12/genetic-screeni ng-parents-can-prevent-cancer-albinism-sickle-cell-children/. [Last accessed on 2018 Jul 15].
32Pasquali R, Pelusi C, Genghini S, Cacciari M, Gambineri A. Obesity and reproductive disorders in women. Hum Reprod Update 2003;9:359-72.
33Sneed ML, Uhler ML, Grotjan HE, Rapisarda JJ, Lederer KJ, Beltsos AN. Body mass index: Impact on IVF success appears age-related. Hum Reprod 2008;23:1835-9.
34Wang J, Sauer MV.In vitro fertilization (IVF): A review of 3 decades of clinical innovation and technological advancement. Ther Clin Risk Manag 2006;2:355-64.
35Pereira N, Setton R, Petrini AC, Lekovich JP, Elias RT, Spandorfer SD. Is anti-müllerian hormone associated with IVF outcomes in young patients with diminished ovarian reserve? Womens Health (Lond) 2016;12:185-92.
36Hart R, Khalaf Y, Lawson R, Bickerstaff H, Taylor A, Braude P. Screening for HIV, hepatitis B and C infection in a population seeking assisted reproduction in an inner London hospital. BJOG 2001;108:654-6.
37ESHRE Capri Workshop Group. Intracytoplasmic sperm injection (ICSI) in 2006: Evidence and evolution. Hum Reprod Update 2007;13:515-26.
38Haas J, Zilberberg E, Dar S, Kedem A, Machtinger R, Orvieto R. Co-administration of GnRH-agonist and hCG for final oocyte maturation (double trigger) in patients with low number of oocytes retrieved per number of preovulatory follicles – A preliminary report. J Ovarian Res 2014;7:77.
39De Vos A, Staessen C, De Rycke M, Verpoest W, Haentjens P, Devroey P, et al. Impact of cleavage-stage embryo biopsy in view of PGD on human blastocyst implantation: A prospective cohort of single embryo transfers. Hum Reprod 2009;24:2988-96.
40Kirkegaard K, Hindkjaer JJ, Ingerslev HJ. Human embryonic development after blastomere removal: A time-lapse analysis. Hum Reprod 2012;27:97-105.
41Sugawara A, Sato B, Bal E, Collier AC, Ward MA. Blastomere removal from cleavage-stage mouse embryos alters steroid metabolism during pregnancy. Biol Reprod 2012;87:4, 1-9.
42Dumoulin JC, Bras M, Coonen E, Dreesen J, Geraedts JP, Evers JL. Effect of Ca2+/Mg2+-free medium on the biopsy procedure for preimplantation genetic diagnosis and further development of human embryos. Hum Reprod 1998;13:2880-3.
43Staessen C, Platteau P, Van Assche E, Michiels A, Tournaye H, Camus M, et al. Comparison of blastocyst transfer with or without preimplantation genetic diagnosis for aneuploidy screening in couples with advanced maternal age: A prospective randomized controlled trial. Hum Reprod 2004;19:2849-58.
44Stern HJ. Preimplantation genetic diagnosis: Prenatal testing for embryos finally achieving its potential. J Clin Med 2014;3:280-309.
45Gleicher N, Weghofer A, Barad D. Preimplantation genetic screening: “established” and ready for prime time? Fertil Steril 2008;89:780-8.
46Gu YF, Zhou QW, Zhang SP, Lu CF, Gong F, Tan YQ, et al. Inner cell mass incarceration in 8-shaped blastocysts does not increase monozygotic twinning in preimplantation genetic diagnosis and screening patients. PLoS One 2018;13:e0190776.
47McArthur SJ, Leigh D, Marshall JT, de Boer KA, Jansen RP. Pregnancies and live births after trophectoderm biopsy and preimplantation genetic testing of human blastocysts. Fertil Steril 2005;84:1628-36.
48McArthur SJ, Leigh D, Marshall JT, Gee AJ, De Boer KA, Jansen RP. Blastocyst trophectoderm biopsy and preimplantation genetic diagnosis for familial monogenic disorders and chromosomal translocations. Prenat Diagn 2008;28:434-42.
49Scott RT Jr., Upham KM, Forman EJ, Zhao T, Treff NR. Cleavage-stage biopsy significantly impairs human embryonic implantation potential while blastocyst biopsy does not: A randomized and paired clinical trial. Fertil Steril 2013;100:624-30.
50Ashiru OA, Ogbeche R, Oladimeji DM, Iloabachie E, Osumah O. Trophectoderm biopsy for preimplantation genetic testing (PGT) for sickle cell anemia: Successful outcome in a developing country. Fertility and Sterility 2017;108:e266.
51van der Ven K, Montag M, van der Ven H. Polar body diagnosis – A step in the right direction? Dtsch Arztebl Int 2008;105:190-6.
52Michalska D, Jaguszewska K, Liss J, Kitowska K, Mirecka A, Łukaszuk K. Comparison of whole genome amplification and nested-PCR methods for preimplantation genetic diagnosis for BRCA1 gene mutation on unfertilized oocytes-a pilot study. Hered Cancer Clin Pract 2013;11:10.
53Braude P, Pickering S, Flinter F, Ogilvie CM. Preimplantation genetic diagnosis. Nat Rev Genet 2002;3:941-53.
54Wang Q, Chow JF, Yeung WS, Lau EY, Lee VC, Ng EH, et al. Preimplantation genetic diagnosis using combined strategies on a breast cancer patient with a novel genomic deletion in BRCA2. J Assist Reprod Genet 2014;31:1719-26.
55Rechitsky S, Shulman LP, Pakhalchuk T, Prokhorovich M, San Ramon G, Kuliev A. Reproductive outcome of 128 PGT cycles for Breast cancer. Fertil Steril 2016;127:56.
56Mateu E, Rodrigo L, Peinado V, Milán M, Campos I, García-Herrero S. Preimplantation genetic testing for translocations and interchromosomal effect assessed by array CGH. Reprod BioMed Online 2018;36Suppl 1:e20-21.
57Zegers-Hochschild F, Adamson GD, de Mouzon J, Ishihara O, Mansour R, Nygren K, et al. International committee for monitoring assisted reproductive technology (ICMART) and the World Health Organization (WHO) revised glossary of ART terminology, 2009. Fertil Steril 2009;92:1520-4.
58Desmyttere S, De Rycke M, Staessen C, Liebaers I, De Schrijver F, Verpoest W, et al. Neonatal follow-up of 995 consecutively born children after embryo biopsy for PGD. Hum Reprod 2012;27:288-93.
59Rodriguez-Wallberg KA, Oktay K. Fertility preservation and pregnancy in women with and without BRCA mutation-positive breast cancer. Oncologist 2012;17:1409-17.
60Horowitz M, Wilner N, Alvarez W. Impact of event scale: A measure of subjective stress. Psychosom Med 1979;41:209-18.
61Woodson AH, Muse KI, Lin H, Jackson M, Mattair DN, Schover L. Breast cancer, BRCA mutations, and attitudes regarding pregnancy and preimplantation genetic diagnosis. Oncologist 2014;19:797-804.
62Derks-Smeets IA, Gietel-Habets JJ, Tibben A, Tjan-Heijnen VC, Meijer-Hoogeveen M, Geraedts JP, et al. Decision-making on preimplantation genetic diagnosis and prenatal diagnosis: A challenge for couples with hereditary breast and ovarian cancer. Hum Reprod 2014;29:1103-12.
63Doolin B, Motion J. Christian lay understandings of preimplantation genetic diagnosis. Public Underst Sci 2010;19:669-85.
64Schenker JG. Religious views on assisted reproductive technologies. J Assist Reprod Genet 1992;9:3-9.
65Garcia B, Brind'Amour K. Evangelium Vitae (1995), by Pope John Paul II. Embryo Project Encyclopedia; November, 2007. Available from: http://embryo.asu.edu/handle/10776/1735. [Last accessed on 2018 Aug 18].
66Serour GI, Aboulghar MA, Mansour RT. Bioethics in medically assisted conception in the Muslim world. J Assist Reprod Genet 1995;12:559-65.
67Olesen A, Nor SN, Amin L. Religious scholars' attitudes and views on ethical issues pertaining to pre-implantation genetic diagnosis (PGD) in Malaysia. J Bioeth Inq 2016;13:419-29.
68Fasouliotis SJ, Schenker JG. Preimplantation genetic diagnosis principles and ethics. Hum Reprod 1998;13:2238-45.
69Medical Advisory Secretariat.In vitro fertilization and multiple pregnancies: An evidence-based analysis. Ont Health Technol Assess Ser 2006;6:1-63.
70Ashkenazi J, Farhi J, Dicker D, Feldberg D, Shalev J, Ben-Rafael Z. Acute pelvic inflammatory disease after oocyte retrieval: Adverse effects on the results of implantation. Fertil Steril 1994;61:526-8.
71Sunkara SK, La Marca A, Seed PT, Khalaf Y. Increased risk of preterm birth and low birthweight with very high number of oocytes following IVF: An analysis of 65 868 singleton live birth outcomes. Hum Reprod 2015;30:1473-80.
72Cimadomo D, Capalbo A, Ubaldi FM, Scarica C, Palagiano A, Canipari R, et al. The impact of biopsy on human embryo developmental potential during preimplantation genetic diagnosis. Biomed Res Int 2016;2016:7193075.
73Shenfield F, Pennings G, Devroey P, Sureau C, Tarlatzis B, Cohen J. Taskforce 5: Preimplantation genetic diagnosis. Hum Reprod 2003;18:649-51.
74Menon U, Harper J, Sharma A, Fraser L, Burnell M, ElMasry K, et al. Views of BRCA gene mutation carriers on preimplantation genetic diagnosis as a reproductive option for hereditary breast and ovarian cancer. Hum Reprod 2007;22:1573-7.
75Staton AD, Kurian AW, Cobb K, Mills MA, Ford JM. Cancer risk reduction and reproductive concerns in female BRCA1/2 mutation carriers. Fam Cancer 2008;7:179-86.
76Quinn G, Vadaparampil S, Wilson C, King L, Choi J, Miree C, et al. Attitudes of high-risk women toward preimplantation genetic diagnosis. Fertil Steril 2009;91:2361-8.
77Julian-Reynier C, Fabre R, Coupier I, Stoppa-Lyonnet D, Lasset C, Caron O, et al. BRCA1/2 carriers: Their childbearing plans and theoretical intentions about having preimplantation genetic diagnosis and prenatal diagnosis. Genet Med 2012;14:527-34.
78George RP, Lee P. Embryonic human persons. Talking point on morality and human embryo research. EMBO Rep 2009;10:301-6.
79Available from: https://plato.stanford.edu/entries/grounds-moral-status/. [Last accessed on 2018 Jul 23].
80Pal T, Vadaparampil ST. Genetic risk assessments in individuals at high risk for inherited breast cancer in the breast oncology care setting. Cancer Control 2012;19:255-66.
81Lagos Introduces Measures to Sanitise Fertility Practice. Available from: https://www.vanguardngr.com/2019/05/lagos-introduces-measur es-to-sanitise-fertility-practice/. [Last accessed on 2019 Jun 23].
82Okonta PI, Ajayi R, Bamgbopa K, Ogbeche R, Okeke CC, Onwuzurigbo K, et al. Ethical issues in the practice of assisted reproductive technologies in Nigeria: Empirical data from fertility practitioners. Afr J Reprod Health 2018;22:51-8.