Hindawi

BioMed Research International

Volume 2018, Article ID 6287507, 9 pages
https://doi.org/10.1155/2018/6287507

Review Article
Risks in Surrogacy Considering the Embryo: From the
Preimplantation to the Gestational and Neonatal Period

M. Simopoulou ,1,2 K. Sfakianoudis,3 P. Tsioulou ,1 A. Rapani ,1 G. Anifandis ,4

A. Pantou,3 S. Bolaris,5 P. Bakas,2 E. Deligeoroglou,2 K. Pantos,3 and M. Koutsilieris 1

1
Department of Physiology, Medical School, National and Kapodistrian University of Athens, Greece
2
Assisted Conception Unit, 2𝑛𝑑 Department of Obstetrics and Gynecology, Aretaieion Hospital, Medical School,
National and Kapodistrian University of Athens, Greece
3
Centre for Human Reproduction, Genesis Athens Clinic, Greece
4
Department of Histology and Embryology, Faculty of Medicine, University of Thessaly, Greece
5
Assisted Conception Unit, General-Maternity District Hospital “Elena Venizelou”, Greece

Correspondence should be addressed to M. Simopoulou; [email protected]

Received 1 December 2017; Accepted 9 July 2018; Published 17 July 2018

Academic Editor: Jonathan Muraskas

Copyright © 2018 M. Simopoulou et al. This is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Surrogacy is an assisted reproduction-based approach in which the intended parents assign the gestation and birth to another
woman called the surrogate mother. The drivers of surrogacy refer largely to infertility, medical conditions, same-sex couples’
parenting, and cases of diversity regarding sexual identity and orientation. Surrogacy consists of a valid option for a variety of
conditions or circumstances ranging from medical to social reasons. However, surrogacy may be associated with risks during the
preimplantation, prenatal, and neonatal period. It became obvious during the exhaustive literature research that data on surrogacy
and its association with factors specific to the IVF practice and the options available were not fully represented. Could it be that
surrogacy management adds another level of complexity to the process from the ovarian stimulation, the subsequent IVF cycle,
and the techniques employed within the IVF and the Genetic Laboratory to the fetal, perinatal, and neonatal period? This work
emphasizes the risks associated with surrogacy with respect to the preimplantation embryo, the fetus, and the infant. Moreover, it
further calls for larger studies reporting on surrogacy and comparing the surrogate management to that of the routine IVF patient
in order to avoid suboptimal management of a surrogate cycle. This is of particular importance in light of the fact that the surrogate
cycle may include not only the surrogate but also the egg donor, sperm donor, and the commissioning couple or single person.

1. Introduction embryo shares no genetic link with the surrogate mother. In

gestational surrogacy, the embryo results from heterologous
Over the last decades, infertility has become a matter that IVF employing the intended parents’ gametes, or the intended
the majority of infertile couples choose to address. Surrogacy father’s sperm and donor’s oocyte (not the surrogate’s),
has revolutionized the standing options within the assisted or the donor’s sperm and the intended mother’s oocyte.
reproduction field, enabling the gestation and birth of child Alternatively, the embryo could be donated [1–4].
by another woman—the surrogate mother—relinquishing Infertility, medical conditions, diversities regarding sex-
the child after birth to the commissioning parents [1–3]. ual identity and orientation, and matters of social nature
The first type of surrogacy is the traditional (or genetic) reflect the basic drivers behind patients’ decision to pursue
surrogacy, in which the father’s sperm or the donor’s sperm is surrogacy. Women with a severe Müllerian anomaly or a con-
naturally or artificially employed to inseminate the surrogate’s genital absence of uterus and/or vagina are usual candidates
oocyte (homologous IVF). This approach leads to an embryo for surrogacy. The condition of Mayer-Rokitansky-Küster-
genetically linked to the surrogate. The second type is the Hauser Syndrome characterized by a female genotype and
gestational (or host) surrogacy. In this case the implanted phenotype and accompanied with a congenital aplasia of the
2 BioMed Research International

uterus and the vagina [5–7] represents another category of leading to hysterectomy. Any lifestyle that could compromise
patients requiring surrogacy. Further to the above, Complete the infant’s health is barred and a legally bound contract
Androgen Insensitivity Syndrome (CAIS syndrome) where between the commissioning parents and the surrogate must
the uterus and ovaries are absent [8, 9], as well as women be signed, ascertaining all the aforementioned conditions [3].
who have undergone hysterectomy, presents as only few of To date surrogacy may not present a straightforward
the cases where surrogacy is imperative and women may alternative among women of reproductive age. In an interest-
choose this as a path to parenthood. Gestational surrogacy is ing study, when presented with the option, women responded
also recommended in cases of Turner’s Syndrome due to the they would rather opt for uterus transplantation instead,
known cardiac and medical complications in these patients with a percentage of 80% vs 47% [17]. However, we should
[10]. Furthermore, surrogacy may present as an option for take into account that in Sweden—where the data came
women with recurrent miscarriages or unidentified failure from—surrogacy is not an available option according to
of infertility treatment [6]. Heart or renal disease and severe Swedish legislation. Laws and practices regarding surrogacy
Rhesus isoimmunization during pregnancy are valid reasons vary, highlighting the controversial nature of the issue, giving
for the mother to avoid such high risk conditions and hence rise to numerous legal and ethical considerations [14]. This
constitute solid grounds in opting for surrogacy [9]. Other may be significantly attributed to surrogacy’s association
indications for surrogacy are maternal medication for specific with various risks during the preimplantation, prenatal, and
disease treatment that could potentially promote embryo’s neonatal period. The results of surrogacy seem to be satisfying
teratogenesis [11] or even severe genetic problems related to and promising, with a reported rate of up to 60% live births,
the intended parents [12]. Social reasons towards optional as surrogate women tend to be fertile and young [6].
surrogacy may correspond to highly driven career women This article highlights the challenges and considerations
and the stress experienced by the intended mother regarding associated with surrogacy. It uniquely brings to literature
the physical changes and the discomfort associated with the respective associations regarding the preimplantation
her perception on pregnancy [13]. Finally, surrogacy may embryo, the fetus, and the infant. When dealing with a
fulfill same-sex couples’ or even a single parent’s desire surrogate cycle within the IVF set-up, is it possible that the
for a genetically linked family [14, 15]. It is evident that urgency for the cycle, in order to secure an optimal result,
the option of surrogacy corresponds to a wide range of compromises its management? Could these pregnancies,
drivers, extending beyond strictly medical reasons especially being widely characterized as “precious,” result in choices
in today’s era. and practices that ensure the highest percentages of success?
The majority of surrogates report that the main incentive Extrapolating on that concept, could these choices be selected
is altruism, as surrogacy reinforces their self-esteem, despite on nonmedical grounds and hence pose a risk? Is it possible
the fact that financial gain may also be a major consideration. that we lean towards a hyperbole when surrogacy is the case?
In many countries, any payment to gestational carriers is
legally prohibited, solely allowing some financial aid only 2. Risk Factors Regarding the Preimplantation
for pregnancy-related expenses [11, 16]. Specifically, altruistic Embryo of a Surrogate Cycle
surrogacy is adopted in England, in many states of United
States, and in Australia, while commercial surrogacy is Surrogacy goes hand in hand with IVF treatment and every
permitted in India, Ukraine, and California. On the other aspect that this entails. A surrogacy cycle within the IVF
hand, surrogacy is not allowed in Germany, Sweden, Norway, set-up includes superovulation, oocyte retrieval, fertilization
and Italy [13]. techniques, embryo culture, embryo selection, embryo trans-
Prior to initiating procedures, certain factors should be fer, and possibly cryopreservation. It is evident that surrogacy
investigated and valued to ascertain safe outcome for both cycles require the services of IVF irrespectively of infertility
the surrogate and the embryo. The surrogate should undergo etiology. The fact that these embryos are created within the
medical examinations and thorough psychological assess- IVF set-up may leave room for further manipulation of the
ment, in order to be considered suitable. The psychological embryo. Extended culture to the blastocyst level may repre-
assessment evaluates the surrogate’s ability to emotionally sent a straightforward example as it may be believed to secure
sustain gestation and delivery. It has been reported that better implantation potential [18]. Further to that point, these
her status throughout the gestation could affect the child’s embryos may be subjected to genetic testing in the form
individuality and psychological wellbeing [3]. The age of the of Preimplantation Genetic Screening (PGS). PGS may be
surrogate should range from 21 to <35 years for traditional employed in order to enhance and enrich selection criteria
surrogacy and to <45 years for gestational surrogacy [12], and identify the embryos carrying a balanced chromosomal
and her reproductive history profile should include at least complement, thus securing a healthy pregnancy [7, 19]. In this
one previous uncomplicated pregnancy, while not exceeding section we highlight the negative implications related to the
5 deliveries or 3 caesarean sections. However, there have been fact that surrogate babies are in fact IVF babies.
reports on surrogates of advanced age for whom a court
decision may allow their involvement, for instance, in cases 2.1. Risk Factors Related to Controlled Ovarian Stimulation.
when the surrogate is a family member, possibly the mother Both embryo manipulation and environmental factors within
of the commissioning woman. The older surrogate has been the IVF laboratory set-up may allow for epigenetic changes
reported by the media to be a 67-year-old woman serving as during the first stages of embryo development. Under epi-
a surrogate for her daughter who developed uterine cancer genetic influence, the control of gene expression through
BioMed Research International 3

DNA methylation, histone modification, and miRNA could [22]. Undoubtedly, ICSI is considered a safe, efficient, and
be altered [20]. These modifications are heritable despite the routinely employed technique of insemination that has not
fact that they do not alter DNA sequences [21]. With respect been particularly associated with increased chromosomal or
to a surrogate IVF cycle, the superovulation regime is applied congenital abnormalities [24]. However, on account of the
either on the commissioning mother in cases of autologous fact that ICSI practice has emerged in the late 90s [26] the
surrogacy (own oocytes) or on the oocyte donor or on the correlation of ICSI practice and the offsprings’ wellbeing has
actual surrogate. At any rate, it is understandable for the to be further evaluated to delineate whether the procedure or
desired oocyte yield to be high. the couple’s genetic background could be accountable for any
Epigenetic changes could occur due to Exogenous future trends or observations.
Gonadotropins (EGs) exposition. EGs are administered to
the ovary to a secure successful superovulation regime 2.3. Risk Factors Related to Embryo Culture. Aiming to secure
through controlled ovarian stimulation (COS). It has been the highest implantation potential of embryos produced in
proposed that EGs may contribute to epigenetic changes an IVF laboratory and included in a surrogate cycle, it is
in four imprinted genes, peg1, kcnq1ot1, zac, and h19 [18], common to opt for blastocyst culture. However, bypassing all
and may impair oocyte and embryo development [22]. The the benefits associated with this practice [27], the hazardous
strictly clinical nature of IVF does not allow for any attempt or ambiguous results associated with prolonged culture and
to thoroughly examine the preimplantation embryo on an its effect on the preimplantation embryo physiology and epi-
epigenetic assessment level, as these embryos are destined for genetics have been extensively argued [28]. To date and to our
embryo transfer and/or cryopreservation. However, the study knowledge, a study related to blastocyst culture and surrogacy
by Ventura-Lunca et al. demonstrated that these imprinted has yet to be published. Nonetheless, our extensive clinical
genes are associated with fetal growth retardation and issues experience and data mined from available published studies
regarding placental development [18]. Therefore, one could support that blastocyst culture appears to be the culture
extrapolate that these detrimental epigenetic changes exert a method of choice when managing a surrogate cycle. Various
detrimental effect on the preimplantation stage of develop- conclusions could be extrapolated regarding the effect of
ment. Whether the defects on peg1 gene and the methylation media and culture conditions on embryonic development
of h19—during the preimplantation period—are associated and epigenetics [29]. Several studies advocate that culture
with superovulation, the patient’s age, and the delayed oocyte medium may be responsible for a variety of detrimental
maturation or if they were inherited, studies in human trends, namely: abnormal implantation, low implantation
models reveal unclear conclusions. The imprinting defects rate, disorders in developmental pace, low embryo quality,
involved may lead to clinical implications in ART, such as fail- and reduced trophoblast development, as well as embryo cell
ure of the embryo to implant, spontaneous abortion, and/or number and hatching ability [18, 30, 31]. An allegedly, simple,
fetal growth retardation attributed to dysfunctional placentas and justified change in media formulation, such as inclusion
[23]. The data available should be further and thoroughly of serum, could lead to neonatal implications as shown in
examined prior to conquering on the true effects of COS. animals [31], while oxygen concentration has been reported
to affect embryo metabolism, protein synthesis, and function
2.2. Risk Factors Related to ICSI Practice. In a surrogate [18]. Efforts are still focused on formulating and proving the
cycle, aspiring to secure the highest fertilization rates, ICSI optimal media consistency for human embryo culture, as
(Intracytoplasmic sperm injection) may be selected as the mimicking and even improving the in vivo conditions is an
method of choice. On the grounds that fertilization results ongoing process.
on ICSI are reported to be higher than standard IVF [24,
25], often this seems to be a welcomed approach for both 2.4. Risk Factors Related to Embryo Manipulation. In the set-
patients and practitioners. However, is it safe to extrapolate up of ART, transferring a euploid embryo to the surrogate
that surrogacy cycles within the IVF practice are associated mother is of paramount importance. This could ensure that
with higher percentages of ICSI practice? The insemination the possibility of miscarriage, termination of pregnancy, or
technique of ICSI may be related to further impairment of live birth related to a compatible with gestation disorder is
the embryo due to its invasive nature. In comparison to the minimized. In case of chromosomal abnormalities and/or
standard IVF insemination technique, ICSI is a practice that monogenic disorders, Preimplantation Genetic Diagnosis
overturns natural selection. An example of that is the over- and Screening (PGD/PGS) excavate monogenic diseases and
ride of the physiological sperm processes involved during chromosomal abnormalities, numerical or structural, leading
fertilization, for instance, acrosomic reaction [26]. Selecting to the best embryo selection [7, 19, 32]. It is not uncommon
the most adequate sperm for ICSI based on morphology for surrogacy to be proposed as the optimal approach
comes with great responsibility, since in vivo the procedure instead of PDG/PGS application, in cases of patients with
of insemination is performed via strict natural selection recurrent miscarriages or with a reproductive history of
criteria. In this way, spermatozoa with decimated mobility autoimmune loss of pregnancy [33]. Given the option, it is
or increased abnormal morphology may be employed during possible that the commissioning couples decide to further
ICSI in cases of male factor infertility and thus lead to higher subject the embryos—destined to be transferred to a sur-
risk of de novo chromosomal anomalies in the ICSI offspring. rogate uterus—to PGS on the grounds of acquiring more
Studies in mouse models observed that male ICSI offsprings information on their genetic profile [7]. The further embryo
with DNA fragmented sperm had reduced fertility potential manipulation may be opted for in order to enhance the
4 BioMed Research International

selection of embryos to be transferred and therefore increase surrogacy, as the most efficient approach to limit multiple
the pregnancy success rate [7]. In addition to that, one must gestation and preterm birth, which are both accompanied
not fail to report on the possibility that PGS may be requested by adverse perinatal and neonatal outcomes [4, 7, 36]. The
and performed not solely on the grounds of selection criteria elective single embryo transfer is embraced universally as the
to enhance success rates, but aiming to select the embryo of optimal method associated with the best perinatal and neona-
“choice” entering a grey and dangerous territory of eugenics. tal outcomes. However, the question raised is the following:
Is it possible that within the set-up of IVF and surrogacy such could the cohort of preimplantation embryos produced for a
practices are promoted? If so, we should thoroughly weigh the surrogacy cycle be subjected to prolonged culture, in order
advantages and disadvantages of such practice, report on the to enhance selection of the best single embryo and enable
benefits ensured by the additional invasive manipulation the eSET? The risks associated with prolonged culture should
embryos are subjected to, and most importantly ponder on be addressed prior to applying this practice [28]. Further
the bioethical questions raised [16]. to that, PGS has been proposed to enhance and secure the
Various embryo biopsy strategies have been suggested, eSET approach. However, another level of complexity to
such as blastomere biopsy at the cleavage stage, trophecto- manipulating these embryos should be accounted for. This
derm biopsy at the blastocyst stage, polar body, and finally hypothesis may be contradicted; it is however imperative for
morula biopsy. Ensuring a careful embryo manipulation dur- this to be thoroughly examined. On the other hand, eSET may
ing biopsy to maintain its viability is pivotal [32]. However, not be solely linked to prolonged culture or PGS application.
one should never fail to recall that this still remains a highly Recently, the combination of time-lapse imaging with mor-
invasive process associated with negative effects in animal phological parameters has claimed to revolutionize embryo
studies. Biopsy of 1-2 blastomeres at the cleavage stage does selection as it may contribute by identifying aneuploid
not exert a negative effect on the further development of embryos avoiding detrimental effects on the embryo. On the
the embryo [33]. On the other hand, increased body weight same concept, the goal remains to allow for true continuous
coupled with impaired acoustic habituation in male mice off- culture and evade embryo culture disruption. In this context,
springs has been suggested to be related to protein alteration time-lapse technology could assist by minimizing events
as a result of PGS biopsy [22]. These represent just a few of epigenetic changes regarding the preimplantation [37].
findings related to PGS application in animal model studies. Minimizing the already invasive nature of IVF is considered
The argument remains whether any adverse obstetric and to be the holy grail of embryology with time-lapse imaging
neonatal outcomes could be attributed to biopsies performed presenting as the first promising attempt [38].
for PGD or as hypothesized be strictly a result of de novo
alterations or the parental profile contribution. This should 3. Risk Factors Related to the Gestation and
be carefully acknowledged in cases of surrogacy where PGS is the Fetus
applied. Subsequently, in these cases vitrification is inevitable
as it goes hand in hand with blastocyst biopsy. This approach In contradiction to natural conceptions, pregnancies deriv-
is required in order to secure the appropriate time required ing from ART cycles—including surrogacy cycles—may be
for the genetic analysis to be performed. Therefore, embryo related to increased risk of perinatal complications. It has
transfer is ensued at a later stage. Vitrification has revolu- been indicated that the perinatal outcomes of gestational
tionized the application of PGD/PGS, allowing for complex surrogacy in comparison to autologous IVF report no major
and time consuming genetic analysis to be performed, offer- increase in the risks of preterm birth, live birth rate, and
ing results on the whole chromosomal complement of the congenital anomalies [4]. In addition to that, it was con-
embryo tested [34]. Cryopreservation of embryos or blasto- templated that oocyte donation demonstrates poor fetal
cysts is considered to have no major genetic or epigenetic immunological adjustment to allogeneic antigen. As a result,
risks [22, 35]. Partial correction of epigenetic changes that gestational surrogacy appears to be associated with a higher
may occur during vitrification in oocytes or in early cleav- risk of hypertensive disorders than autologous IVF [16]. Prior
age embryos is attributed to specific mechanisms, while in exposure of the embryo to culture medium in the IVF set-
developing blastocysts it completely disappears [21]. Embryo up could contribute to perinatal complications as well, such
manipulation should be carefully considered and ideally as unbalanced fetal placenta development, abnormal fetal
employed on valid grounds referring to medical etiology and growth, and metabolic responses [18]. An increased systolic
not patient’s desire. Embryo biopsy for PGS and subsequent blood pressure in 21-week-old mice with previous IVF culture
vitrification should both be carefully considered in cases of has been indicated, as well as a minor anxiety, psychomotor
surrogacy, where IVF services are strictly employed to enable activity, and special memory in rat embryos [31].
surrogacy procedures. Having access to embryos created in In order to increase implantation rates, the method of
the IVF laboratory should not always translate to using it. multiple embryos transfer is opted for in some IVF cases. This
Invasive practices involve mechanisms that have not been practice is also adopted and perhaps even heightened in the
entirely delineated yet, and hence they remain unpredictable. cases of surrogacy, resulting in multiple gestations with the
obstetric and perinatal complications that these may entail
2.5. Risk Factors Related to the Embryo Transfer Procedure. [14]. IVF-surrogates may present with a lower incidence of
The number of the embryos transferred is characterized third trimester’s complications, such as pregnancy-induced
by controversy and debate. Numerous studies support the hypertension, placenta praevia and abruption, diabetes melli-
elective single embryo transfer (eSET), especially in cases of tus, and hemorrhage, irrespective of whether it was a multiple
BioMed Research International 5

gestation or singleton, in comparison to women subjected to and functional abnormalities which could lead to adulthood
standard IVF. However, it was evident that IVF surrogacy physical or mental defects are minimized. What is more, the
with multiple gestations is associated with increased risk surrogate mother—equally to any pregnant woman—should
of preeclampsia, postpartum hemorrhage, hysterectomy, and adopt an appropriate diet, as nutrition deficiency could
gestational diabetes [39]. In addition to the above, multiple permanently alter the development or function of a specific
pregnancies are related to higher risk of hyperemesis and ane- organ [42].
mia [14]. In light of the above, multiple gestations—especially Without a doubt the psychological and emotional states
in surrogate cycles—should be avoided; thus supporting eSET of the surrogate play a pivotal role in the wellbeing of
practice is highly recommended [7]. In cases of multiple ges- the fetus. Stemming from the behavior and/or the stress
tations associated with challenging obstetric complications, level of the surrogate, her state may translate biologically
selective feticide may be an option. Nevertheless, it consti- to deleterious intrinsic factors that affect the wellbeing and
tutes a risky alternative. Performance of fetal intracardiac development of the fetus. Could it be that the possible lack of
injection of potassium chloride for selective feticide has been acceptance of the surrogate towards recognizing the embryo
re-evaluated due to the high risk it presents to the fetus not and fetus as her own and the possible lack of positive outlook
subjected to the procedure [40]. The use of radiofrequency of the pregnancy may present a risk to the development
ablation interrupting blood flow to the selected fetus is of the fetus? It is suggested that the gestational mother
considered as potentially being the most effective option for may contribute to fetal development, through epigenetics,
any gestational age [41]. It is argued whether parents have the microchimerism (cells are transferred between the fetus and
right to decide for selective feticide, as there is more interac- mother through placenta), and transport of both antibodies
tion between the surrogate’s body and the developing fetuses. and nutrients [1]. Fetal consciousness develops from the
The special conditions and the uniqueness characterizing uterine to breastfeeding period and numerous physiological,
surrogacy, the relationship, and the expectations of the emotional, or environmental messages affect its development.
commissioning couple/person towards the surrogate could Consequently, maternal acceptance or rejection could be a
complicate management. This is a situation understandably stimuli imprinted in human cells. Medical evidence proves
lacking control, a condition which certainly may create the that increased stress hormones in maternal blood, such
basis for a pregnancy associated with an extra level of stress as adrenalin, penetrate placenta and invade to fetal blood,
factors [3]. Exposure to maternal stressors during preg- causing fetal rapid heartbeat or breathing acceleration [43].
nancy activates the hypothalamus-pituitary-adrenal cortex Dar’s interesting study examining all issues from medical
system or hypothalamic–pituitary–adrenal (HPA) axis and to psychosocial and legal exploring data from a large sur-
sympathetic system as well, which provoke hormones’ pro- rogacy program reported an overall mean of 37,9 weeks of
duction, such as CRH (corticotrophin-releasing hormone), gestational age at birth on surrogacy cases and specifically
ACTH (adrenocorticotropin-releasing hormone), cortisol, 38,9 weeks for singletons and 35,8 weeks for multiple births
adrenalin, and noradrenaline in maternal blood [42]. It is evi- [11]. These results seem to be comparable with previous
dent that maternal stress may affect the unborn baby through studies. The maternal complication rate reported by Dar et al.
the secretion of mother’s stress hormones (such as ACTH, was 9.8% which is considerably low due to the fact that surro-
CRH, prolactin, and oxytocin). The increased levels of the gate mothers have a history of previous healthy pregnancies
aforementioned hormones are associated with reduction of without any complications. Fetal anomalies in the same
uteroplacental blood flow, leading to fetal growth restriction study are presented with a prevalence of only 1.8% possibly
(IUGR: Intrauterine Growth Restriction) [42]. Interestingly, attributed to the extensive obstetric history check that the
it has been evaluated via ultrasound examination that fetuses surrogates are subjected to or due to the fact that surrogacy is
of highly anxious women at the 36 gestational weeks present often enabled by oocyte donation [11]. Surrogate candidates
increased bodily activity [42]. What is more, the high levels of are meticulously examined, their background investigation is
hormones may indicate and contribute to automatic abortion, thorough, and their medical profile may be often ideal. On the
structural malformations, and preeclampsia. This may be the other hand, women who conceive naturally do not necessarily
result of depression or anxiety during the first trimester, cou- fulfill all the above prerequisites. Therefore, positive results
pled with high levels of placental CRH and smaller head cir- related to surrogacy with respect to complications may be
cumference, affecting brain growth [42]. Maternal hormones, anticipated, contradicting the notion that complications and
like adrenalin, are produced in maternal blood in cases of complexity may be heightened in surrogacy cycles.
fear and/or discomfort and provoke the stress’ symptoms of
tachycardia and breathe acceleration. In addition, maternal 4. Risk Factors Related to the Neonatal and
stress during the third trimester contributes to preterm the Period Thereafter
uterine activity, leading to preterm delivery, while maternal
stress in the first trimester may lead to low birth weight [43]. Whether factors related to the surrogate pregnancy find their
During the fetal period, the surrogate mother has to way towards affecting the neonatal and the period following is
abide by all agreed limitations, as she is exposed to the same a subject under investigation. Many studies propose that ART
pregnancy risks as any pregnant woman. This means that offsprings—and that extends to surrogacy cases—are prone
she is vulnerable to ectopic pregnancy or even miscarriage to cardiovascular diseases, presenting with higher systolic
[2]. Conformation to limitations indicates avoiding drugs or and diastolic blood pressure, obesity resulting from insulin
alcohol consumption. In this way, risks regarding structural resistance and the impaired glucose metabolism, and thyroid
6 BioMed Research International

dysfunction with high levels of thyroid-stimulating hormone the mother’s malnutrition during pregnancy [18]. To extend
(TSH) [22]. On the other hand, there are reports indicating this to the IVF environment, it has been shown that there
that IVF techniques may not extend to burdened perinatal is clear association between protein deficiency in embryo
and neonatal complications. The study by Chian et al. 2008 culture media and the child’ birth weight [18, 19]. Information
examined 200 infants deriving from three different centers involving nutrition of the surrogate is scarce and difficult
in Canada, born from vitrified oocytes, and concluded that to control or record especially in reflection to perinatal
vitrification had no effect on fetus and baby [44]. data. Therefore, especially in light of the lack of knowledge,
As mentioned above, the practice of multiple embryos it is imperative to evaluate the mode and strength of the
included in the ET may result in multiple gestations often association between nutrition of the surrogate and respective
encountered in surrogacy cycles. These may result in preterm implications on the children.
labour and delivery, in comparison to singleton [2, 5, 39]. Stress levels of the surrogate during gestation could play
Consequently, babies present with low birth weight or they a detrimental role. This exhaustive search did not identify
fail to sustain perhaps even due to prematurity alone or studies reporting on whether maternal stress levels are higher
accompanied by a deformity or abnormality [1]. Further- during a surrogate pregnancy in comparison to nonsurrogate
more, newborns of multiple gestations may present with pregnancy. This fact may highlight a deficit in the literature.
speech delays and developmental handicaps [5], as well as General population studies show a clear association between
cerebral palsy [1]. What is more, prematurity, directly related maternal stress and low birth weight or prematurity [42].
to multiple gestations, contributes to congenital malforma- Neonatal studies on infants from highly anxious mothers
tions and increased rates of caesarean sections, in comparison recorded persistent crying during the first seven months
to singleton [39]. In contrast to the above, a follow-up on of life and neonates characterized by irritability, irregular
babies born through multiple or singleton IVF surrogacy biological functions, and gripes. Later at the age of nine,
showed that motor delays cease at the second year of their these children were classified as overactive and poor sleepers
life [5]. On the other hand, singleton IVF-children present [42, 43]. Prenatal maternal stress plays an important role to
with no further physical anomalies, taking into consideration the infants’ behavior, as studies observed that infants were
that defect embryos often fail to implant. This is in contrast to categorized as antisocial and with low frustration threshold
multiple gestations, which appear to be associated with low- [43]. Ward’s study evidenced a correlation between the
birthweight infants and/or with minor heart and lung defects development of childhood psychopathology and various pre-
[45]. Multiple gestations associated with complications in natal conditions, such as maternal chronic or prenatal stress
surrogate pregnancies may be avoided by opting for eSET and anxiety, maternal acceptance of pregnancy, and some
as discussed above and managed employing the practice excessive physical reactions to pregnancy like vomiting [47].
of selective feticide. This, especially in complex cases, may Psychiatric observations showed that maternal stress during
entail a therapeutic nature by creating safer conditions for the pregnancy plays a pivotal role to the appearance of Attention
surrogate’s health as well for the infant to be. However, it is Deficit Hyperactivity Disorder (ADHD), schizophrenia, and
best to avoid reaching the point when it becomes a necessity depression. Characteristically, depressive adults have high
and selective feticide becomes an option. The complications levels of blood cortisol and CRH hormones [42].
associated with its practice are numerous. Neurodevelop- Children born through gestational surrogacy are legally
mental impairment, including cognitive, motor, and behav- protected, through the anonymity of the donor and surro-
ioral aspects, has been detected in 6.8% of the reported cases gate’s data. However, the child has the right to be informed
following selective feticide, while this finding appears to be in a specific manner on the way that he/she was born and
more frequent in comparison to the general population [46]. be informed of his/her origins in general [48]. Many studies
The solution to challenges originating from multiple ges- record a positive child’s reaction when information is released
tations is for the IVF set-up to promote further the practice regarding the surrogacy, either traditional or gestational [49].
of elective single embryo transfer to avoid multiple gestations The science of prenatal and perinatal psychology reveals
and the considerable risks associated with them [7, 36]. The that every stimulus recorded to the child’s consciousness
Ethics Committee of the American Society for Reproduction significantly determines its behavior as an adult, both phys-
(ASRM) underlies the need for the gestational surrogate to ical health and mental balance. Moreover, it defines the
be protected, by inclusively informing her regarding all the relationships that the child forms throughout life. In addition
possible risks multiple pregnancies entail. On that concept, to that, many clinical studies assume that the embryo’s con-
it becomes apparent that the final decision regarding the science is formed during the intrauterine period and that the
number of embryos to be transferred should be the surrogate’s perception and the feelings of the surrogate during gestation
[14]. may affect infant development majorly. Medical evidence
Nutrition of the surrogate is an important factor that supports the fact that various neurohormones are transferred
could pose a risk. Insufficient nutrition during pregnancy from mother to fetus during pregnancy. These are pivotal
plays an important role to the child’s or even to the adult’s for fetal brain development, normal neural system’s function,
health, as it may be responsible for the development of and the future child’s self-confidence and intelligence [43].
cardiovascular diseases, allergies, hypertension, diabetes, or Good communication and feelings of acceptance act catalyt-
either schizophrenia [42]. This is also confirmed by the ically on the communication between mother and fetus and
Barker hypothesis, according to which the appearance of consequently contribute to important developmental aspects
metabolic syndromes in adulthood may be attributed to extending even to the child’s speech ability [3].
BioMed Research International 7

It may be that trigger points regarding the psychological the surrogate embryo and the IVF embryo present with
status of an expectant mother are the same between surro- overlap on various concepts of management, as anticipated.
gates and nonsurrogates. If that can be safely hypothesized, This study set out to delineate and highlight the similarities
then negative factors such as prenatal maternal stress, per- and differences of a surrogate cycle embryo in comparison to
ceptions, and feelings will be expected to equally affect both the standard IVF embryo, regarding the options and at times
groups at the same extent. However, is it equally safe to the clinical practice. Any complications arising from the
assume that such issues and detrimental effects will burden IVF practice enabling surrogacy are clearly associated with
the infants of a surrogate pregnancy further? Additional stud- a more complex management in comparison to standard IVF
ies are required to enrich our knowledge on such important cases. Surrogate embryo, fetus, neonate, and infant should be
issues on surrogacy. Could it be that a surrogate pregnancy, identified and examined thoroughly, as the risks related to
even though it is a product of consent and informed decision these entities may differ. Acquiring a better understanding of
of the surrogate, may differ with respect to the feelings what dictates these differences constitutes the base for a safer
involved regarding a natural occurring desired pregnancy? practice.
With respect to the psychological effect on the children
born through surrogacy there are conflicting reports. Chil- Conflicts of Interest
dren born from a surrogate mother do not differ in their
behavior [2, 3]. These offspring, at the age of two, seem to have The authors declare that there are no conflicts of interest
no difficulties in their social integration and their cognitive regarding the publication of this article.
and emotional development. Later, at the ages of three, seven,
and ten, their psychological prosperity was found to be at the Authors’ Contributions
same levels as the other peer-to-peer children [3].
M. Simopoulou and K. Sfakianoudis conceived and designed
Another study examined the impact of surrogacy—gene-
the study. M. Simopoulou, P. Tsioulou, and A. Rapani and
tically linked or not—on the children’s psychological wellbe-
S. Bolaris performed the literature search and contributed to
ing during the first three years of their life, as well as during
the structure of the manuscript. P. Tsioulou, A. Rapani, and
the preschool period at the age of seven. The results assessed
A. Pantou contributed to drafting the manuscript. M. Simo-
family processes, such as warmth, communication among
poulou and G. Anifandis edited the manuscript. P. Bakas,
members, and conflict. The study concluded that, at ages
E. Deligeoroglou, K. Pantos, and M. Koutsilieris revised the
of one, two, and three, children were overall unaware of
manuscript. All authors approved the final draft. M. Simo-
the way they were born and family relationship appeared
poulou and K. Sfakianoudis are co-first authors. K. Pantos
to be warmer and more enjoyable, in comparison to family
and M. Koutsilieris have joint last authorship.
processes regarding naturally conceived children. Later, at the
age of seven, children presented a more positive relationship
with their mothers, in contrast to natural conception families. References
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