Modern Technology (E.G., IVF)
In Vitro Fertilization (IVF) together with Intra Cytoplasmic Sperm Injection (ICSI) are the two major technologies applied in modern Assisted Reproduction Technology (ART)
In 1978, the world’s first “test-tube baby” was born in England (Steptoe and Edwards 1978). Her name was Louise Brown, and she was the first human born after fertilization of an oocyte by a sperm in a laboratory instead of inside the female body. Such in vitro fertilization (IVF) was at first developed primarily for treating infertility in female patients with obliterated fallopian tubes or other pathologies. Following this initial breakthrough, IVF was accompanied by other technological advances that together constitute modern assisted reproductive technologies (ART). One of these technologies is intra cytoplasmic sperm injection (ICSI). ICSI is primarily used in couples where infertility arises due to a low sperm cell count in the ejaculate. The ICSI operator holds the oocyte in a micropipette and injects it with one of the few sperm cells present under the microscope, thereby fertilizing the oocyte (Palermo et al. 1992). Some of the other technologies constituting modern assisted reproduction are the use of donor oocytes and donor sperm; the cryopreservation of sperm, oocyte, and embryos; the surgical extraction of sperm from the testicle or epididymis, in addition to uterus transplantation and the comprehensive genetic testing; and morphological screening of cells and tissues in both donors and recipients (Niederberger et al. 2018). By putting these technologies to work, assisted reproduction technology has become a common part of most modern health care systems. In several countries ART now accounts for 4–5% of babies born annually (European IVF Monitoring Consortium 2017). In 2017, it was estimated that more than six million children had been born worldwide after ART thus far.
Assisted Reproductive Technologies in Infertile Patients
Assisted reproduction’s main use to date has been the treatment of infertile heterosexual couples. The diagnosis of infertility in these couples is based on WHO criteria, which states that infertility is “a disease of the reproductive system defined by the failure to achieve a clinical pregnancy after 12 months or more of regular unprotected sexual intercourse” (Zegers-Hochschild et al. 2017). Treating such couples with IVF has several possible evolutionary effects as selection pressures differ between natural and assisted reproduction (Hanevik et al. 2016). These differences in selection pressures occur at different stages in the reproductive process.
The oocyte: In natural reproduction, the ovaries in general release one oocyte each menstrual cycle. Before ovulation, this oocyte has been through a long phase of growth and development (Hsueh et al. 2015) where at least the final phases of maturation are under tight control by female reproductive hormones. In IVF, this final phase of maturation is manipulated by pharmacological means so that the number of oocytes that are available for ovulation in the ovary is higher, typically around ten. Instead of being released into the female abdomen, the mature oocytes are collected by ultrasound guided aspiration and delivered to the IVF laboratory for fertilization. This means that many of the oocytes that become fertilized in IVF would not have been so in natural reproduction. The selection pressure for timing of oocyte maturation to the naturally occurring variations in female reproductive hormones is thus less in assisted reproduction.
The sperm: After being ejaculated into the vagina in natural reproduction, the sperm has to swim through the cervix of the uterus, pass the uterine cavity and then find its way into one of the two fallopian tubes containing an oocyte that is available for fertilization. Large interspecies variation in sperm morphology is one indication that navigating the internal female genital organs, finding, and finally fertilizing an oocyte is a process with a wide scope for the effect of selection pressures. In IVF, the selection pressures are different in that the ejaculated sperm goes through one or more steps of rinsing and preparation before the sperm is either released in close proximity to the oocyte (IVF) or injected into it (ICSI). Compared to the natural situation, there is very little propulsion and navigation involved for the sperm, and in ICSI the mechanism for fertilization is also very different. Hence, the selection pressures that influence which sperm will have its DNA represented in the next generation are systematically changed in assisted reproduction.
The embryo: The fertilized oocyte develops into an embryo that in natural reproduction travels down the fallopian tube and implants in the uterine cavity about 7 days after fertilization (Franasiak et al. 2016). In the IVF laboratory, the embryo develops in an incubator under controlled temperatures and gas concentrations, submerged in a commercially available embryo cultivation media. From the ten collected oocytes, typically one embryo will be transferred to the uterus after 1–5 days of cultivation in the lab, and surplus normally developed embryos will be cryopreserved for transfer in a later cycle. The decisions concerning which embryo to transfer and cryopreserve are taken by embryologist, who typically use criteria such as pace of development, embryo morphology and certain developmental landmarks to aid their decisions. The selection pressures for complying with algorithmically determined developmental milestones are not present in the natural situation. Compared to the natural situation, the embryo in assisted reproduction is also exposed to more mechanical stress, strong light, and exogenous chemicals, altering selection pressures.
The couple: Although controversial, a complete analysis of differences in selection pressures between natural and assisted reproduction must include a mention of the barriers that exist for couples to enter an IVF program in the first place. At least in some countries the law prevents people with serious psychiatric illness for instance to undergo assisted reproduction. Also IVF is an expensive treatment, so in many countries infertile couples with low income do not have equal chance of becoming pregnant as those infertile couples who can afford IVF. This is a systematic difference compared to the natural situation, where the chance of pregnancy does not depend on your psychiatric history or your income.
Assisted Reproduction in Fertile Patients
The use of assisted reproductive technologies is ever more common also in patients who are not infertile by the WHO definition. This includes same sex couples, some cases of oocyte cryopreservation (so-called social freezing), and some cases of preimplantation genetic testing. Assisted reproduction in lesbian couples includes the use of donor sperm either for intrauterine insemination or for conventional IVF. Social freezing occurs when a female wishes to cryopreserve her oocytes at a young age, say when she finishes university, so that she can build a career and find a suitable husband without having to worry as much about her declining fertility if this takes longer than she expects. Assisted reproduction is also very much a part of preimplantation genetic testing, where a couple who either have or carry certain heritable diseases can make sure the “sick” gene for this disease is not transferred to their offspring. In most such cases IVF is preformed, and the resulting embryos are genetically tested to make sure only embryos without the “sick” gene in question are transferred to the uterus. These, and other, applications of assisted reproduction technologies in fertile patients may also have evolutionary implications. The case of genetically testing the embryo for instance is, in principle, applying a very specific selection pressure. However, as the evolutionary implications will vary widely depending on the specifics of the technique, analyzing their systematic difference to natural reproduction is unfruitful.
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