21.12.2021

Medical aspects of surrogate motherhood

Surrogacy is associated with a wide range of factors that increase maternal and perinatal risks. The use of in vitro fertilization and embryo transfer technologies determines the higher frequency of multiple pregnancies which enhances the risk of cesarean section, premature birth, the low body weight of newborns, etc. in case of surrogacy. Genetic differences and immunogenetic reactions increase the risk of preeclampsia, placental pathology, miscarriage, intrauterine growth retardation. Hormonal disbalance under the effect of adverse factors during surrogate pregnancy may initiate prenatal reprogramming of morphogenesis through epigenetic mechanisms. This can affect the organogenesis and predispose to susceptibility to various diseases. Psychological factors and emotional link between a surrogate mother and fetus are associated with increased levels of stress-releasing system hormones, which affect the formation of neurohumoral systems of the fetus and can modulate its mental development.

Keywords: surrogacy, pregnancy, medical complications, perinatal risks.

With the introduction of state-of-the-art assisted reproductive technologies (ART), to- day, in vitro fertilization (IVF) and surrogacy have become commonplace. Surrogacy is defined as a contract under which a woman (gestational carrier/surrogate) gives birth to a child for another couple, usually infertile, who are also called intended parents [1]. Such a contract can be concluded based on altruistic or commercial grounds. The latter option involves payment to the surrogate mother of the reward exceeding necessary medical expenses. While commercial surrogacy is banned in many developed countries, the multibillion-dollar business of cross-border reproductive care, including international surrogacy, is thriving in developing countries [2]. Today, Ukraine, along with Russia, Thailand, Nepal, Georgia, and Mexico, is one of the few world countries where surrogacy is legal and cheap [3]. Despite the pandemic, many Ukrainian women have become surrogate mothers for infertile foreign couples.

Specialists in various fields have different attitudes to commercial surrogacy. In many countries, legally permissible is only altruistic surrogacy. However, in addition to purely legal and ethical issues, there are also some essential medical and psychological aspects associated with surrogacy. Do women who have chosen the fate of a gestational surrogate know the price they pay for the reward received by them? This article covers medical and psychological aspects that parties to the Surrogacy contract should be aware of.

Pregnancy is a period of complex biopsychological transformations that include physical, physiological, and psychological changes. During pregnancy, not only the uterus and other organs of the female reproductive system change, but also internal organs, the woman’s neuroendocrine system, metabolic processes, and immunity [4]. It is no secret that surrogacy is accompanied by a series of medical and psychological risks which inevitably cause stress. This is primarily associated with the fact that the surrogacy cycle, regardless of the cause of genetic parents’ infertility, involves the use of IVF procedures, including super-ovulation of the genetic mother, oocyte selection, in vitro fertilization, embryo culture, selection, and transfer. The fact that embryos for surrogacy are created in the conditions of IVF, on the one hand, forms the possibility of further manipulation, including preimplantation genetic testing (screening) [1], and on the other — implies the inevitability of the next step — embryo transfer into the body of the gestational carrier. To improve the surrogate mother’s endometrial receptivity, significant doses of estrogen and progesterone are administered. Also, it should be noted that far from all embryos are usually transferred while some of them can be cryopreserved and others destroyed.

Unfortunately, embryo transfer is not always successful. In 2003, only 40% of embryo transfers resulted in pregnancies, and only in 60% of cases, a surrogate pregnancy ended in a successful delivery [5]. However, over time, the statistics have improved significantly with the enhancement of ART. Today, according to the websites and marketing materials of IVF clinics in the United States, the success rate of surrogacy reaches about 75%, and in the case of confirmed pregnancy, the probability of healthy childbirth reaches 95%. Similar data can be seen on the websites of Ukrainian clinics involved in the business of surrogacy. However, they sometimes fail to announce the number of embryo transfers required for a successful pregnancy.

According to the 2008 report of the Society for Assisted Reproductive Technology, out of 2,502 cycles of gestational surrogacy per- formed in registered IVF (від англ.: in vitro fertilizatio) clinics, only 39.45% of cycles were successful, leading to 987 childbirths with 1,395 children born from gestational surrogates [6]. 2013 data of US clinics show that 46% of registered cycles for gestational carriers failed [7]. Obviously, not all embryo transfers are successful and lead to a gestational surrogate’s pregnancy.

Yet successful implantation does not mean successful pregnancy. In developed countries, like Canada, the incidence of clinical pregnancy (reaching 20 weeks or more) in surrogacy is 73-75% [8, 9], while in a quarter of cases, the pregnancy ends in miscarriage. The statistics in developing countries is less optimistic. According to the Mexican IVF clinic, only 30 (22.2%) out of 135 cycles were successful.

With this in mind, a share of successful pregnancies that ended in childbirth accounted for 33.3% with the birth of twins in 24% [10].

Indeed, surrogacy is associated with a high incidence of multifetation [10]. Based on a meta-analysis of 55 publications, the incidence of multiple pregnancies in surrogacy ranged from 2.6% to 75.0%, depending on the country, study design and sample size [11]. Turning to the Canadian study, among gestational surrogates, twin pregnancy was registered in 28.6% of cases, while 0.02% of pregnancies resulted in the birth of triplets [9].

Why is surrogacy more often associated with multiple pregnancies? The answer is simple — to increase the likelihood of successful implantation and pregnancy, several embryos are usually transferred. Quite recently, the American Society for Reproductive Medicine (ASRM) and the European Society of Human Reproduction and Embryology have introduced guidelines on single embryo transfer, yet today, only 15 to 20% of clinics follow these single embryo transfer standards [12].

Because of the high probability of multiple pregnancies, surrogacy is associated with a high incidence of childbirth through cesarean section. Thus, according to [9], the incidence of vaginal birth in gestational surrogates was 76.7%, while the caesarean section was performed in 23.3%. These figures are much higher than the WHO threshold of 10-15%, although the incidence of cesarean delivery varies by country and even by the hospital. Although the caesarean section is technically a simple surgery, it is associated with a risk of complications ranging from 3.3% to 54.4%, according to various authors, depending on the socioeconomic level of the country where the study was conducted and associated factors, and includes bleeding, lesions of adjacent organs, infectious complications, hysterectomy and even death [13, 14].

According to the literature, pregnancy complications in gestational surrogacy occur in 9.8% of cases [9]. Though the provided data seem low compared to natural pregnancy, such comparisons are not correct. This is because, for surrogacy, only young and healthy women with successful reproductive experience are selected. Indeed, candidates for surrogate mothers must be between the ages of 21 and 35, without obsessive habits, with a history of healthy childbirth and a proven state of health. There are no women with chronic diseases of kidneys, liver, reproductive system among them, nor patients with diabetes or other endocrine diseases, that most often cause complications during pregnancy and after childbirth.

Hypertension and pre-eclampsia prevail among complications of pregnancy in surrogate mothers, just like in the pregnancy with donor eggs. Moreover, numerous studies confirmed that compared to conventional (autologous) IVF, both conditions — surrogacy and pregnancy with the use of donor eggs — are accompanied by a significantly higher incidence of placental pathology, as well as other complications, including intrauterine growth retardation, prematurity, and congenital anomalies 15]. In addition, the authors noted a fairly high risk of postpartum complications, such as intrauterine or postpartum hysterectomy, stroke, and blindness [16].

Previous medical and obstetric history of potential gestational carriers should be studied thoroughly, and candidates should be carefully consulted about the potential risks associated with the procedure.

It is essential that these complications are being developed against the background of local and systemic immunological disorders. Genetic factors are at the core of these pregnancy complications in the case of surrogacy. The material of embryos being transferred to the uterus of surrogates is absolutely foreign to women because it contains genomes of intended (genetic) parents. According to the laws of immunity, all exogenous bodies must be eliminated from the organism through the mechanisms of cell-mediated and humoral immunity. Unsurprisingly, the examination of the placenta in allogeneic pregnancy revealed signs of immunological impairment in the form of chorioamnionitis, chronic villitis, chronic histiocytic intervillositis and lymphoplasmacytic deciduitis [17]. During surrogacy, the number of cytotoxic T lymphocytes (CD8) and plasma cells (CD138) increased in the placenta with a decrease in the number of regulatory T cells (CD25/CD4/FOXP3), which are responsible for the formation of the mother’s immune tolerance to «foreign» fetus’ biological material. Such immunogenetic mechanisms explain the significantly lower level of successful implantation and considerably higher risk of miscarriages (up to 49.6%), premature birth (up to 21.6%), and the development of complications in surrogate mothers [19].

Immunoinflammatory placental lesions affect not only the medical risks of the surrogate mother but also fetus formation. The prospective experimental model [19] with the transfer of inbred embryos to surrogate mothers with different genotypes showed that genetic differences between the surrogate’s body and that of the fetus, as well as the mother’s immunocompetence, affected the offspring’s phenotype through epigenetic mechanisms. Thus, the influence of the surrogate mother’s genotype on body weight and distribution of adipose tissue in adult offspring was revealed. In addition, genetic differences caused a shift in the offspring’s immune response in terms of humoral immunity and functional activity of macrophages, which may further affect the body’s vulnerability to various infectious and immune-mediated diseases. Researchers do not preclude that additional immune system shifts may be caused by microchimerism associated with transplacental cell exchange between the surrogate mother and the fetus [20].

Identified immunogenetic changes correlated with surrogate’s hormone levels, particularly progesterone, although it is not the only hormone that can mediate the relationship between the mother’s and the child’s bodies. Studies by Swedish researchers showed that a baby’s body composition, size and weight are related to the mother’s levels of adipokines and leptin [21], which vary widely depending on diet, metabolism, and physical activity. The hypothalamic-pituitary-adrenal system of the fetus is known to be formed under the influence of the mother’s hormones and the steroid-producing function of the placenta. Excessive and/ or steady stress, anxiety or depression of the surrogate mother adversely affect both body and the formation of the hypothalamic-pituitary-adrenal axis of the fetus, its stress reactivity and immune system [4]. It is obvious that the mother’s stress can affect the unborn child through stress hormone release in the surrogate mother (such as ACTH, corticotropin-re- leasing hormone, prolactin, and oxytocin) [22]. Elevated levels of these hormones may cause a decreased uteroplacental blood flow leading to intrauterine growth retardation [23]. High levels of stress hormones may lead to early termination of pregnancy, premature birth, the development of pre-eclampsia and fetal development disorder. Moreover, according to the hypothesis proposed by Barker DJ [24], maternal factors, including changes in diet and stress, may affect intrauterine conditions and the risk of developing certain diseases in children in adulthood [25]. The connection was confirmed between the influence of adverse factors during pregnancy and the increased risk of coronary heart disease, heart disease, hypertension, diabetes mellitus, metabolic syndrome through the mechanisms of prenatal reprogramming using epigenetic mechanisms [26, 27]. The study of these mechanisms resulted in the understanding of the importance of pregnancy and lactation in determining the health of the fetus [28]. In addition, understanding of the mechanisms of prenatal reprogramming has become the basis for the development of a system of interventions aimed at improving individual health [29].

From this perspective, the psycho-emotional state of the gestational surrogate mother plays an important role in the formation of the regulatory systems of the fetus. At the same time, psychologists suggest that surrogacy is more often associated with stress. Key emotional issues that cause stress in surrogate mothers include [12]:

  • Forced suppression of feelings for the
  • Fear and anxiety that the child has health
  • Relationships with the family, relatives, and genetic parents of the fetus; fear of her husband’s reactions in marriage and sexual
  • Concerns about financial compensation from genetic parents.
  • Doubts about informing her own children about the type of
  • Concerns and anxiety related to informing relatives and friends.
  • Consequences of surrogacy: complications of pregnancy, hospital stay, cesarean section, the recovery period after childbirth.
  • Religious problems of those involved in the process of surrogacy in the absence of reli- gious and social acceptance.

Unsurprisingly, about 20% of surrogate mothers experience depression; 39% of women suffered from feelings of guilt/doubt or despair about the decision to become a surrogate; 33% have a risk of post-traumatic stress disorder. With negative IVF results, the incidence of depression or anxiety disorders and significant stress increased to 65% [11, 29]. Another important psycho- logical aspect of the surrogate pregnancy is the emotional connection with the baby during its prenatal development. During normal pregnancy, a woman’s internal experience and feelings change, and attachment to the baby, emotional connection with it is formed [31]. The degree of relationship and attachment between mother and fetus affects the mental health of infants considerably. It is not without reason that prenatal care in many countries around the world involves the development of attachment skills. Is this connection, emotional involvement, and attachment to the baby equal in the case of surrogate motherhood compared to a normal pregnancy? Unfortunately, the research confirms that NO. Gestational surrogates interacted with the fetus less than normal mothers [32, 33], and vice versa, some surrogate mothers were forced to suppress their feelings for the child or even felt guilty before their own genetic children. On the other hand, according to a ten-year longitudinal study [34], no effect was found between surrogacy and the psychosomatic condition of children, hence actual consequences of such potential effect are yet to be studied.

Thus, to sum up, surrogacy is associated with a wide range of factors which when combined increase maternal and perinatal risks. These factors include:

  • The use of in vitro fertilization and embryo transfer determines the higher incidence of multiple pregnancies and thus enhances the risk of cesarean section, premature birth, the low body weight of newborns, higher risk of bleeding, etc.
  • Genetic differences and relevant immunogenetic reactions that increase the risk of pre-eclampsia, placental pathology, miscarriage, intrauterine growth retardation.
  • Hormonal disbalance under the effect of adverse factors during surrogate pregnancy may, through epigenetic mechanisms, initiate prenatal reprogramming of morphogenesis by affecting the baby’s organ and system formation, its susceptibility to diseases.
  • Psychological factors and emotional link between a surrogate mother and fetus are associated with increased levels of stress-releasing system hormones, which affect the formation of neurohumoral systems of the fetus and may modulate its mental development.

Oksana Sulaieva
Medical Laboratory CSD, Kyiv, Ukraine
Ukrainian Catholic University, Lviv, Ukraine

Acknowledgments
Author thanks Maria Yarema for her great assistance in writing this manuscript (Lviv, Ukraine).

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