1

Complications of In-Vitro Fertilization

Bianca Chaser, Julia Hum, Sarah Leonard, Emily Testa

Youngstown State University

NURS 3749: Nursing Research

Randi Heasley

April 9, 2023
COMPLICATIONS OF IN-VITRO FERTILIZATION 2

PICO

This literature review researched complications in-vitro fertilization could cause in

pregnancies. The following PICOT question was developed: “In women of childbearing age,

does the use of in vitro fertilization compared to natural conception increase the risk of maternal

and fetal complications?”

Search Strategy

A variety of techniques were used in order to conduct a search strategy for the

information included in this literature review. Words individually key searched included; “IVF,

Complications (placental and maternal), in vitro fertilization, and natural conception” per the

Maag library A-Z research database. Sources used were found from MEDLINE (PubMed),

MEDLINE with Full Text (EBSCO), and CINAHL Plus with Full Text (EBSCO). A large

variety of information was emanated from a variation of studies and scholarly articles published

between 2018-2023, with the exception of a few earlier publishing dates that were approved

before use. These sources were then put together to form the following literature review;

exploring Complications of In-vitro Fertilization.

COMPLICATIONS OF IN-VITRO FERTILIZATION 3

Complications of In-Vitro Fertilization

Throughout the years, natural conception has become an issue for a multitude of women.

The impact has affected their hope of sustaining a pregnancy and creating a family. While often

thought to be a common and instinctive phenomenon, pregnancy is a very intricate, delicate, and

complex process. Due to groundbreaking discoveries in scientific-based practice and

technological findings, the use of artificial insemination has been able to aid a plethora of

couples to achieve the goal of an expanded family. Techniques that involve the manipulation of

an oocyte externally, in retrospect to the body, are defined as assisted reproductive technology,

with in-vitro fertilization (IVF) being the most common form. With all surgical and non-surgical

procedures, there runs a risk of both fetal and maternal detriments that are often discouraging to

all parties involved. Physically, IVF can have several maternal effects on the body such as

bloating, cramping, and breast tenderness, as well as a myriad of fetal complications consisting

of birth defects. Psychologically, IVF can be challenging for couples. The emotional stress of

undergoing fertility treatments can be significant, and the uncertainty of success can be difficult

to manage.

As mentioned before, IVF is a medical procedure that involves manually fertilizing an

egg with sperm outside of the body and then implanting the fertilized embryo into the uterus.

The oocyte, or developing egg, is fertilized in a petri dish where it is intended to grow, develop,

and mature into pregnancy. Because this is such a monumental advancement in medical

discovery, IVF now accounts for 1.6% of all live births in the United States and 4.5% of live

births in Europe (Choe & Shanks, 2023). Treatment has offered couples who are severely

struggling with infertility an alternative method to receive the ultimate desired outcome, a baby.

The preparation for IVF is a convoluted course of action that requires several evaluations before
COMPLICATIONS OF IN-VITRO FERTILIZATION 4

the treatment cycle. There is an importance in recognizing that this choice of fertilization calls

for rigorous and tedious steps that may be exhausting, draining, and dispiriting. Adverse effects

can dictate how well the pregnancy may follow suit.

In comparison to IVF, natural conception appears to occur in a much smoother and easier

fashion than multi-step implantation. To fully understand both concepts of IVF and natural

conception, it is essential to be aware of what fertility denotes. According to the American

Society for Reproductive Medicine fertility, by definition, is the capacity to produce a child

(2021, p.1). Mothers who can conceive naturally do not necessitate the fact that there were no

complications with conception, but it does mean that they were able to produce a fetus with no

simulated medical assistance. Natural insemination takes place between a male and female

through sexual intercourse where the sperm of the male internally fertilizes the egg released by

the female. Difficulties arise in this population when there is an intent to get pregnant, but the

time window is not working in the favor of the couple, meaning they are doing everything

correctly to get pregnant, but not getting the favored ramification. There are fertility-aware

methods that can be utilized such as the “fertile window,” which is best explained as the 6-day

interval ending on the day of ovulation where, in theory, the viability of both the sperm and

oocyte is maximal and the chance of getting pregnant is high. However, this does not ensure that

pregnancy will be the outcome which can be disheartening to the trying couple.

Now that there is a clear idea of the two processes, one can better grasp the objective of

what complications can arise with IVF. To name just a few, complications may include the risk of

infection, preterm labor, fetal abnormalities, and continuity of infertility. Microbial

contamination refers to the presence of microorganisms such as bacteria, fungi, viruses, and

protozoans in a sterile environment. Despite the best efforts of laboratories and clinics to keep
COMPLICATIONS OF IN-VITRO FERTILIZATION 5

their premises and equipment free from microbes, contamination can still occur due to various

reasons including human error, poor maintenance of equipment, environmental factors, and

cross-contamination. Laboratories and clinics rely on human resources to carry out various tasks,

including sterilization procedures. However, even a minor mistake can compromise the sterility

of equipment and surfaces, leading to microbial contamination.

Automated equipment such as autoclaves and incubators require regular maintenance

checks to ensure that they are functioning optimally. If not properly maintained, such equipment

can harbor microbes that may contaminate other surfaces or samples. Various environmental

factors such as humidity and temperature affect the growth and survival of microorganisms.

Failure to control these factors may lead to the proliferation of unwanted microbes in the

laboratory or clinic. Cross-contamination is the transfer of microorganisms from one sample or

surface to another. This can occur if proper precautions such as disinfecting equipment and using

separate workspaces are not observed.

As the number of women seeking IVF continues to rise, it is necessary to evaluate the

potential maternal complications that may increase with the procedure. There have been several

studies conducted investigating the risk of complications associated with IVF compared to

natural conception in women of childbearing age. Research shows that IVF is associated with an

increased risk of maternal complications that in turn increase maternal morbidity and mortality.

One complication that prompted research on how IVF increases the risk of these complications

compared to spontaneous conception was the increased presence of hypertensive disorders of

pregnancy.

According to Chih et al., an evaluation of 85 studies in a meta-analysis including 405,920

IVF pregnancies and 8,122,210 spontaneous conception pregnancies was completed. The studies
COMPLICATIONS OF IN-VITRO FERTILIZATION 6

conducted compared the presence of hypertensive disorders of pregnancy and preeclampsia

between those two methods of conception. Preeclampsia is a complication of pregnancy in which

a woman has a new onset of high blood pressure in addition to either high levels of protein in the

urine or other organ dysfunctions. To analyze the data, they used an odds ratio. An odds ratio

(OR) is a measure of the association between an exposure and an outcome. The OR represents

the odds that an outcome will occur given a particular exposure, compared to the odds of the

outcome occurring in the absence of that exposure. According to the studies conducted, the

results reflected that IVF pregnancies had higher odds of hypertensive disorders of pregnancy

reflecting an odds ratio of 1.70, and preeclampsia reflecting an odds ratio of 1.59 in comparison

to the spontaneous conception group (2021). Any odds ratio greater than one indicates an

increased occurrence of the event in the study. Meaning, those who developed a hypertensive

disorder of pregnancy were 1.70 times more likely to have undergone IVF than those who used

spontaneous conception. Those who developed preeclampsia were 1.59 times more likely to have

undergone IVF than those who used spontaneous conception. Therefore, this meta-analysis

confirmed that IVF pregnancies are at higher odds of hypertension disorders of pregnancy and

preeclampsia than spontaneous pregnancies.

A reliable comprehensive review, conducted by Ledesma-Montes et al., addressed

obstetric complications in pregnancies that resulted from IVF. In this study, they analyzed results

from thirty-seven articles that examined research over a decade. Their research reflected a higher

rate of complications occurring with IVF in comparison to spontaneous pregnancies. According

to the research, the IVF group had a higher incidence of postpartum hemorrhage (6.7% vs. 3.6%)

and placenta accreta (2.7% vs. 0%) in comparison to spontaneous conception pregnancies

(2020). Postpartum hemorrhage occurs when a woman experiences excessive bleeding after
COMPLICATIONS OF IN-VITRO FERTILIZATION 7

giving birth. Placenta accreta is a condition when the placenta grows deeply in the wall of the

uterus and after delivery, parts of it may remain attached when they should all be expelled. This

can cause excessive bleeding after birth as well. The IVF pregnancy group also had a higher

incidence of hypertension with an odds ratio of 1.27, gestational diabetes with an odds ratio of

3.05, placenta previa with an odds ratio of 2.18, and a high prevalence of cesarean sections

(Ledesma-Montes et al., 2020). These results indicate IVF increases the odds of women

developing these complications in comparison to women who conceive spontaneously. It is clear

IVF has enabled women to achieve pregnancy that once seemed impossible as they faced

infertility. It is also clear that conception through the process of IVF can place them at a higher

risk for some maternal complications. As this process evolves and attracts more women battling

infertility, research continues to evolve surrounding this topic as well. If the benefit of this

process outweighs the risks for infertile women, it is important to be aware of this research and

the increased risk of maternal complications that has been found for proper precautions and

management to be acknowledged throughout the IVF process.

On top of IVF imposing risks for the mother of the baby, numerous risks are associated

with the fetus, as well. While having to convert to conceiving artificially is a very hard decision

in itself for many parents, understanding the risk factors for the fetus is very important for

parents to be able to make these decisions. According to Fu et al., “Emerging evidence has

shown that in-vitro fertilization (IVF) is associated with higher risks of certain placental

abnormalities or complications, such as placental abruption, preeclampsia, and preterm birth”

(2022, p. 2).

The placenta plays a very important role in every pregnancy. The placenta is responsible

for ensuring that adequate nutrients, blood, gas, and immunity are given to the fetus during
COMPLICATIONS OF IN-VITRO FERTILIZATION 8

pregnancy to develop correctly, and without this, no fetus would develop. Placental abruption

occurs when the placenta detaches from the wall of the uterus, where it naturally resides for the

full term of pregnancy until delivery. This occurring prematurely puts the fetus at risk for many

further complications such as; hemorrhage, fetal death, and decelerations in the fetus’ heart rate

due to not enough oxygen being supplied to the baby while in the womb. Through studies, it was

found that the use of IVF greatly increases the risk of this placental abruption happening, thus

imposing a greater chance of other issues for the fetus occurring, such as preterm labor and birth,

putting the baby at risk for low birth weight.

Preterm birth is defined as any baby born alive too early, specifically before 37 weeks

gestation. Full-term is any baby being born between 39 weeks and 40 weeks. Many modifiable

and nonmodifiable elements can contribute to preterm birth, such as the mother's BMI, low or

high maternal age, race, being pregnant with multiples, substance abuse such as tobacco and

alcohol during pregnancy, and the use of assisted reproductive technology, such as IVF. Babies

that are delivered before 37 weeks are at an increased risk of a great number of health problems,

such as low birth weight of the fetus. Low birth weight can put the fetus at risk for other health

complications throughout its entire life. Many health factors can contribute to preterm birth

occurring, and the use of assisted reproductive technology, such as IVF is one of them.

There is an increased risk for mothers becoming pregnant with multiples when using IVF

because there is usually more than one embryo being transferred during the procedure. What this

means is essentially multiple eggs are harvested from the mother and fertilized, because not

every egg will be successful when using this method of artificial reproductive technologies.

Using this method of harvesting and implanting multiple eggs puts mothers who use IVF at a

higher chance to carry twins or triplets. Being pregnant with multiples often puts the babies at
COMPLICATIONS OF IN-VITRO FERTILIZATION 9

risk of being born prematurely, while also increasing the risk of other placental abnormalities for

the fetus occurring. While this is not the only reason that IVF leads to these issues, it is a

contributing factor.

In 2018, a study conducted in China was used to measure and determine if the use of IVF

contributed to placental abnormalities and complications. To conduct this study, 1663 women

who used IVF to conceive and 3326 with spontaneous pregnancies (natural conception)

contributed to the data. There was a significantly higher incidence of gestational diabetes,

hypertensive disorders, and placenta previa in mothers who used IVF compared to those who did

not (Fu et al., 2022, p. 1). Why IVF leads to health issues for the fetus is not a single, clear

answer. Many medications are used to induce ovulation, and all of these artificial medications

can directly harm the gametes and embryos during development (Jin et al., 2013, p. 4). This is

one reason that the use of IVF can directly contribute to placental abnormalities.

The final part of the IVF process includes the implantation of one or two fertilized

embryos into the womb. From that point, the pregnancy continues as a natural pregnancy. IVF

pregnancies and spontaneous pregnancies possess specific risks of their own. Failure to implant

the embryos into the uterus lining is the biggest downfall in IVF pregnancies. The unsuccessful

attempt may be due to embryo or uterus complications.

One example of uterine complications include ovarian hyperstimulation syndrome

(OHSS). This syndrome occurs in women who are prescribed injections of hormonal medication

that stimulate the development of eggs in the ovaries. An excessive amount of hormones can lead

to a heightened response of stress in the maternal partner. In addition, OHSS has been connected

to a higher abortion rate. According to research by Delvigne, a study was conducted involving

104 severe cases of OHSS that occurred after the use of IVF. The research found that higher
COMPLICATIONS OF IN-VITRO FERTILIZATION 10

abortion rates were present in OHSS patients when compared to IVF patients without OHSS

during the same 6-year period. However, in spontaneous pregnancies OHSS is extremely rare. In

some cases, it can occur in women with hypothyroidism, polycystic ovary syndrome (PCOS),

and an overall increased production of human chorionic gonadotropin (hCG). IVF’s high

incidence of multiple pregnancies increases the chances of OHSS, which leads to higher fetal

complications (Delvigne, 2003, p. 86).

In spontaneous pregnancies there are a multitude of potential issues including: high blood

pressure, gestational diabetes, infections, preeclampsia, preterm labor, depression, miscarriage,

and stillbirth. Although with IVF, the imperilment of inducing labor as well as the need for a

cesarean section increases compared to a vaginal birth. Furthermore, cesarean deliveries in itself

are associated with increased maternal and neonatal morbidity and mortality. When comparing

these two methods of conception, research conducted by Elias indicates that IVF pregnancies are

associated with higher odds of cesarean section compared to spontaneous conceptions (2021,

p.1). The research shows that natural conception pregnancies are more likely to result in a natural

delivery compared to IVF pregnancies.

In addition to IVF, natural conception has associated risks that can involve the health of

both the mother and the fetus, resulting in high-risk pregnancies. According to a study conducted

by Nik Hazlina et al., research displays that maternal mortality is a major public health issue

worldwide. It accounts for 85% of maternal deaths, with approximately 40%–50% of maternal

deaths being preventable (2020, p. 12). Many practices and screenings can be used to combat

these maternal deaths in high-risk pregnancies associated with natural conception. Risk

assessment tools can be used if they can prevent adverse effects in both mother and fetus. The

results of the study show a deeper detail into complications during pregnancy, “About 18% of
COMPLICATIONS OF IN-VITRO FERTILIZATION 11

high-risk pregnant women developed SMM conditions. While about 5% of low-risk pregnant

women developed SMM conditions, seven had hypertensive disorders, four had hemorrhagic

disorders, and seven were managed for their complications” (Nik Hazlina et al., 2020, p. 23).

The complications due to natural conception impact a wide variety of different systems of the

body. Preventing these complications comes with early detections and screenings, and the best

option for the mother and infant is to regularly attend doctor appointments.

There are many complications with both natural conception and IVF conception. The

risks with both may be preventable with early detection of the condition and following up with

the patient’s doctor. Some practices to prevent and maintain these risks include; taking folic acid

supplements, eating well, staying active, and monitoring the infant movement. Any type of

pregnancy involves risks, but being able to detect and prevent maternal and fetal complications

will ensure a safe pregnancy and delivery for the mother and infant.

In conclusion, research shows that although the process of IVF has had a great deal of

success, it does come with a few risks and benefits that should be considered. The most obvious

benefit of IVF is the fact that it provides couples with a chance to have biological children when

other methods, such as adoption or surrogacy, are not an option. It can also help reduce the

instances of genetic diseases that may be passed on from parent to child. In many cases, the egg

or sperm used in IVF are screened to select the healthiest cells for fertilization. At the same time,

there are some risks associated with IVF. These include a higher risk of multiple births,

premature birth, risks to the baby due to increased use of fertility drugs, and the potential for

more than one baby to be implanted in the uterus. In addition, IVF may be expensive, and there

is no guarantee it will be successful.

COMPLICATIONS OF IN-VITRO FERTILIZATION 12

In the end, IVF is a personal decision that couples should make with care. It is important

to discuss the risks and benefits with a doctor and weigh the pros and cons before making a

decision. However, for some couples, IVF can be a chance for them to have biological children

of their own and that option can be a blessing.

COMPLICATIONS OF IN-VITRO FERTILIZATION 13

References

Chih, H. J., Elias, F., Gaudet, L., Velez, M. (2021). Assisted reproductive technology and

hypertensive disorders of pregnancy: systematic review and meta-analyses. BMC

pregnancy and childbirth, StatPearls. 21(449). Retrieved March 15, 2023, from

https://doi.org/10.1186/s12884-021-03938-8

Choe , J., Shanks, A. L. (2023). National Center for Biotechnology Information. In Vitro

Fertilization. Retrieved April 9, 2023, from

https://www.ncbi.nlm.nih.gov/books/NBK562266/

Delvigne, A., Rozenberg, S. (2003). Review of clinical course and treatment of ovarian

hyperstimulation syndrome (OHSS). Human reproduction update, 9(1), 77–96. Retrieved

March 20, 2023, from https://doi.org/10.1093/humupd/dmg005

Elias, F., Gaudet, L., Lodge-Tulloch, N., Pudwell, J., Smith, G., Velez, M., Walker, M., (2021).

Caesarean section in pregnancies conceived by assisted reproductive technology: a

systematic review and meta-analysis. BMC Pregnancy Childbirth 21, 244. Retrieved

March 16, 2023, from https://doi.org/10.1186/s12884-021-03711-x

Jin, F., Lu, Y., Wang, N. (2013). Long-term follow-up of children conceived through assisted

reproductive technology. Journal of Zhejiang University. Science. B, 14(5), 359–371.

Retrieved March 13, 2023, from https://doi.org/10.1631/jzus.B1200348

Fu, Y., Kong, F., Li, R., Qiao, J., Shi, H., Wang, Y., Zhao, Y. (2022). Placental abnormalities and

placenta-related complications following in-vitro fertilization: Based on national

hospitalized data in China. Frontiers. 13. Retrieved April 5, 2023, from

https://www.frontiersin.org/articles/10.3389/fendo.2022.924070/full
COMPLICATIONS OF IN-VITRO FERTILIZATION 14

Ledesma-Montes, J., León-Durán, G., Madrazo-Cabo, J., Morales-González, I.,

Oliveros-Montiel, A., Sedeño-Monge, V. (2020). Complications in pregnancies achieved

by assisted reproduction. Gaceta medica de Mexico, 156(2), 156–163. Retrieved March

11, 2023, from https://doi.org/10.24875/GMM.M20000352

Nik Hazlina, N., Norhayati, M., Rajbanshi, S., (2020). High-risk pregnancies and their

association with severe maternal morbidity in Nepal: A prospective cohort study.

National Center for Biotechnology Information, PloS one, 15(12), Retrieved March 20,

2023, from https://doi.org/10.1371/journal.pone.0244072

The American Society for Reproductive Medicine (2021). Optimizing Natural Fertility: A

committee opinion - ASRM. Optimizing natural fertility: a committee opinion. Retrieved

April 9, 2023, from

https://www.asrm.org/globalassets/asrm/asrm-content/news-and-publications/practice-gui

delines/for-members/optimizing_natural_fertility.pdf