IN VITRO FERTILIZATION

 IN VITRO FERTILIZATION (IVF)

Rev Fr Utazi Prince Marie Benignus Zereuwa 

June 18 2024

INTRODUCTION

In vitro fertilization (IVF) is the joining of the egg of a woman and the sperm of a man in a laboratory dish. In vitro means “outside the body”. Fertilization means the sperm has attached to and entered the egg.

Normally, an egg and sperm are fertilized inside the body of a woman. If the fertilized egg attaches to the lining of the womb and continues to grow, a baby is born about 9 months later. This process is called natural or unassisted conception.

In a natural pregnancy, an egg develops and matures in the ovary. Ovulation is when the ovary releases that egg. The sperm travel through the uterus and into the fallopian tube to find the egg and penetrate it, which leads to fertilization. The fertilized egg, or embryo, then attaches itself to the uterus wall and begins developing into a baby.

However, IVF may be an option for the following reasons: a person is unable to get pregnant naturally; a person or couple is diagnosed with unexplained infertility; male factor infertility or abnormal sperm parameters; a persons fallopian tubes are blocked

According to the Human Fertilization and Embryology Authority in the U.K., one IVF treatment cycle can take between 36 weeks. However, a person may require more than one cycle depending on their risk factors and the success rate of the treatment.

IVF is a form of assisted reproductive technology (ART). This means special medical techniques are used to help a woman become pregnant. It is most often tried when other, less expensive fertility techniques have failed.

In 1978, Louise Brown became the first baby born via IVF conception. Robert Edwards and Patrick Steptoe, who collaborated on the procedure, are considered the pioneers of IVF.

IN VITRO FERTILISATION (IVF)

In vitro fertilization (IVF) is a type of assistive reproductive technology (ART). It involves retrieving eggs from the ovaries of a woman and fertilizing them with sperm. This fertilized egg is known as an embryo. The embryo can then be frozen for storage or transferred to the uterus of a woman.

IVF is a complex series of procedures used to help with fertility or prevent genetic problems and assist with the conception of a child. During IVF, mature eggs are collected (retrieved) from ovaries and fertilized by sperm in a lab. Then the fertilized egg (embryo) or eggs (embryos) are transferred to a uterus. One full cycle of IVF takes about three weeks. Sometimes these steps are split into different parts and the process can take longer.

IVF is the most effective form of assisted reproductive technology. The procedure can be done using the eggs and sperm of the couple. Or IVF may involve eggs, sperm or embryos from a known or anonymous donor. In some cases, a gestational carrier, that is, someone who has an embryo implanted in the uterus might be used.

IVF helps people with infertility who want to have a baby. Because it is expensive and invasive, couples often try other fertility treatments first. These may include taking fertility drugs or having intrauterine insemination.

Depending on your situation, IVF can use: your eggs and the sperm of your partner; your eggs and donor sperm; donor eggs and the sperm of your partner; donor eggs and donor sperm; donated embryos

Your doctor can also implant embryos in a surrogate, or gestational carrier. This is a woman who carries your baby for you.

PROCEDURE /STEP FOR IN VITRO FERTILIZATION (IVF)

There are five (5) basic steps in IVF, and they are: ovarian stimulation, egg retrieval, sperm retrieval, fertilization and embryo transfer. One cycle of IVF can take about two to three weeks. More than one cycle may be needed.

A. OVULATION INDUCTION/OVARIAN SIMULATION/ SUPER OVULATION

The start of an IVF cycle begins by using synthetic hormones to stimulate the ovaries to produce multiple eggs, rather than the single egg that typically develops each month. Multiple eggs are needed because some eggs will not fertilize or develop normally after fertilization.

Superovulation is also known as controlled ovarian hyperstimulation. Fertility medications contain either luteinizing hormone or follicle-stimulating hormone. These hormones make the ovaries produce more eggs than usual. Transvaginal ultrasound scans can monitor the growth and progress in the ovaries.

Several different medications may be used, such as:

(i) Medications for ovarian stimulation. To stimulate your ovaries, you might receive an injectable medication containing a follicle-stimulating hormone (FSH), a luteinizing hormone (LH) or a combination of both. These medications stimulate more than one egg to develop at a time.

(ii) Medications for oocyte maturation. When the follicles are ready for egg retrieval, generally after eight to 14 days, you will take human chorionic gonadotropin (HCG) or other medications to help the eggs mature.

(iii) Medications to prevent premature ovulation. These medications prevent your body from releasing the developing eggs too soon.

(iv) Medications to prepare the lining of your uterus. On the day of egg retrieval or at the time of embryo transfer, your doctor might recommend that you begin taking progesterone supplements to make the lining of your uterus more receptive to implantation.

(v) Your doctor will work with you to determine which medications to use and when to use them.

(vi) Typically, you will need one to two weeks of ovarian stimulation before your eggs are ready for retrieval. To determine when the eggs are ready for collection, you may have:

(vii) Vaginal ultrasound, an imaging exam of your ovaries to monitor the development of follicles, fluid-filled ovarian sacs where eggs mature

(viii) Blood tests, to measure your response to ovarian stimulation medications, estrogen levels typically increase as follicles develop, and progesterone levels remain low until after ovulation

SOMETIMES IVF CYCLES NEED TO BE CANCELED BEFORE EGG RETRIEVAL FOR ONE OF THESE REASONS:

(i) Inadequate number of follicles developing

(ii) Premature ovulation

(iii) Too many follicles developing, creating a risk of ovarian hyperstimulation syndrome

OTHER MEDICAL ISSUES

If your cycle is canceled, your doctor might recommend changing medications or their doses to promote a better response during future IVF cycles. Or you may be advised that you need an egg donor.

(In summary, Administration of fertility drugs to stimulate ovaries to produce eggs: We strive to attain multiple egg production because not every egg will develop fully or fertilize after retrieval. A transvaginal ultrasound is used to examine and monitor the ovaries routinely during egg recruitment. At the appropriate time, more medication is given to complete the maturation of eggs and trigger ovulation. People respond to medication differently, so the response is unique to each individual.)

B. EGG RETRIEVAL

Egg retrieval can be done in the clinic or in the office of your doctor 34 to 36 hours after the final injection and before ovulation.

During egg retrieval, the woman will be sedated and given pain medication. The usual retrieval method is Transvaginal ultrasound aspiration. An ultrasound probe is inserted into the vagina to identify follicles. Then a thin needle is inserted into an ultrasound guide to go through the vagina and into the follicles to retrieve the eggs. If the ovaries are not accessible through transvaginal ultrasound, an abdominal ultrasound may be used to guide the needle. The eggs are removed from the follicles through a needle connected to a suction device. Multiple eggs can be removed in about 20 minutes. After egg retrieval, you may experience cramping and feelings of fullness or pressure.

Mature eggs are placed in a nutritive liquid (culture medium) and incubated. Eggs that appear healthy and mature will be mixed with sperm to attempt to create embryos. However, not all eggs may be successfully fertilized.

(In summary, Egg Collection: Eggs are retrieved through a minor surgical procedure that uses ultrasound imaging to guide a hollow aspiration needle through the pelvic cavity to remove the eggs. This procedure takes about 10 to 20 minutes.)

C. SPERM RETRIEVAL

If you are using the sperm of your partner, then, a semen sample needs to be provided at the clinic or at the office of your doctor, in the morning of the day of egg retrieval. 

The method of collecting the sperm is typically through masturbation. Other methods, such as testicular aspiration which is the use of a needle extract sperm directly from the testicle; and surgical procedure, are sometimes required. Donor sperm also can be used. Sperm are separated from the semen fluid in the laboratory

(In summary, Sperm collection: The male produces a fresh semen sample prepared for insemination. If the man is unavailable on the day of egg collection, a frozen sample can be used instead. This means that a sperm cryopreservation procedure had been scheduled before IVF.)

D. INSEMINATION, FERTILIZATION, AND EMBRYO CULTURE

Fertilization can be attempted using two common methods:

(I) CONVENTIONAL INSEMINATION. During conventional insemination, healthy sperm and mature eggs are mixed and incubated overnight.

(II) INTRACYTOPLASMIC SPERM INJECTION (ICSI). In ICSI, a single healthy sperm is injected directly into each mature egg. ICSI is often used when semen quality or number is a problem or if fertilization attempts during prior IVF cycles failed.

In certain situations, your doctor may recommend other procedures before embryo transfer.

ASSISTED HATCHING

About five to six days after fertilization, an embryo hatches from its surrounding membrane (zona pellucida), allowing it to implant into the lining of the uterus. If you're an older woman, or if you have had multiple failed IVF attempts, your doctor might recommend assisted hatching. 

Assisted Hatching is a technique in which a hole is made in the zona pellucida just before transfer to help the embryo hatch and implant. Assisted hatching is also useful for eggs or embryos that have been previously frozen as the process can harden the zona pellucida.

PREIMPLANTATION GENETIC TESTING

Embryos are allowed to develop in the incubator until they reach a stage where a small sample can be removed and tested for specific genetic diseases or the correct number of chromosomes, typically after five to six days of development. 

Embryos that do not contain affected genes or chromosomes can be transferred to your uterus. While pre-implantation genetic testing can reduce the likelihood that a parent will pass on a genetic problem, it cannot eliminate the risk. Prenatal testing may still be recommended.

(In summary, Insemination: The sperm and eggs are mixed and stored in an incubator to promote fertilization. In cases where the probability of fertilization is low, a process called intra cytoplasmic sperm injection (ICSI), whereby a single sperm cell is injected into a single egg. The eggs are monitored to confirm fertilization and cell cleavage.)

E. EMBRYO TRANSFER

Embryo transfer is done at the clinic or at the office of your doctor and usually takes place two to five days after egg retrieval. The woman might be given a mild sedative. The procedure is usually painless, although you might experience mild cramping.

The doctor will insert a long, thin, flexible tube called a catheter, into the vagina of the woman, through her cervix and into her uterus. A syringe containing one or more embryos suspended in a small amount of fluid is attached to the end of the catheter. Using the syringe, the doctor places the embryo or embryos into the uterus of the woman.

If successful, an embryo will implant in the lining of the uterus of the woman about six to 10 days after egg retrieval.

After the embryo transfer, the woman can resume her usual daily activities. However, the ovaries of the woman may still be enlarged. However, it is advisable that the woman should avoid vigorous activity, which could cause discomfort.

(In summary, Embryo transfer: Embryos are usually transferred into the uterus of the woman 3 or 5 days after egg retrieval and fertilization. Under ultrasound guidance, a catheter containing the selected embryos is inserted into the uterus, where the embryos are deposited. This process takes about 5 minutes and is usually painless. However, some women experience mild discomfort.)

IVF success rates

For 2019, the CDC estimated that the percentage of intended egg retrievals that resulted in live birth deliveries was: 52.7% among people aged under 35 years, 38% among people aged between 3537 years, 24.4% among people aged between 3840 years, 7.9% among people over the age of 40

These statistics vary depending on where the procedure takes place.

TYPICAL SIDE EFFECTS OF INVITRO FERTILIZATION INCLUDE:

Passing a small amount of clear or bloody fluid shortly after the procedure, due to the swabbing of the cervix before the embryo transfer; Breast tenderness due to high estrogen levels; Mild bloating; Mild cramping; Constipation

If you develop moderate or severe pain after the embryo transfer, contact your doctor. He or she will evaluate you for complications such as infection, twisting of an ovary (ovarian torsion) and severe ovarian hyperstimulation syndrome.

RESULTS

About 12 days to two weeks after egg retrieval, your doctor will test a sample of your blood to detect whether you are pregnant. If you are pregnant, your doctor will refer you to an obstetrician or other pregnancy specialist for prenatal care. If you are not pregnant, you will stop taking progesterone and likely get your period within a week. If you do not get your period or you have unusual bleeding, contact your doctor. If you are interested in attempting another cycle of in vitro fertilization (IVF), your doctor might suggest steps you can take to improve your chances of getting pregnant through IVF.

THE CHANCES OF GIVING BIRTH TO A HEALTHY BABY AFTER USING IVF DEPEND ON VARIOUS FACTORS (FACTORS AFFECTING HAVING A HEALTHY BABY THROUGH IVF), INCLUDING:

MATERNAL AGE: The younger you are, the more likely you are to get pregnant and give birth to a healthy baby using your own eggs during IVF. Women age 41 and older are often counseled to consider using donor eggs during IVF to increase the chances of success.

EMBRYO STATUS: Transfer of embryos that are more developed is associated with higher pregnancy rates compared with less-developed embryos (day two or three). However, not all embryos survive the development process. Talk with your doctor or other care provider about your specific situation.

REPRODUCTIVE HISTORY: Women who have previously given birth are more likely to be able to get pregnant using IVF than are women who've never given birth. Success rates are lower for women who've previously used IVF multiple times but didn't get pregnant.

CAUSE OF INFERTILITY: Having a normal supply of eggs increases your chances of being able to get pregnant using IVF. Women who have severe endometriosis are less likely to be able to get pregnant using IVF than are women who have unexplained infertility.

LIFESTYLE FACTORS: Women who smoke, typically have fewer eggs retrieved during IVF and may miscarry more often. Smoking can lower a woman's chance of success using IVF by 50%. Obesity can decrease your chances of getting pregnant and having a baby. Use of alcohol, recreational drugs, excessive caffeine and certain medications also can be harmful.

Talk with your doctor about any factors that apply to you and how they may affect your chances of a successful pregnancy.

In addition, IVF can be time-consuming, expensive and invasive. If more than one embryo is transferred to the uterus, IVF can result in a pregnancy with more than one fetus (multiple pregnancy).

WHY YOU SHOULD CONSIDER IVF/ADVANTAGES OF IVF

Increased chances of a healthy baby; Increased chances of pregnancy; Decreased miscarriages; Increased possibility of having multiple babies

USES/ADVANTAGES OF IVF

(a) In vitro fertilization (IVF) is a treatment for infertility or genetic problems. If IVF is performed to treat infertility, you and your partner might be able to try less-invasive treatment options before attempting IVF, including fertility drugs to increase production of eggs or intrauterine insemination; a procedure in which sperm are placed directly in the uterus near the time of ovulation.

(b) Women who do not have a functional uterus or for whom pregnancy poses a serious health risk might choose IVF using another person to carry the pregnancy (gestational carrier). In this case, the eggs of the woman are fertilized with sperm, but the resulting embryos are placed in the uterus of the gestational carrier.

(c) Sometimes, IVF is offered as a primary treatment for infertility in women over age 40. IVF can also be done if you have certain health conditions. This will lead us into discussing those who should consider IVF

WHO SHOULD CONSIDER IVF

Women older than 40 years; Women with blocked fallopian tube; Men battling with low sperm count; Couples with infertility For example, IVF may be an option if you or your partner has:

(1) Fallopian tube damage or blockage. Fallopian tube damage or blockage makes it difficult for an egg to be fertilized or for an embryo to travel to the uterus.

(2) Ovulation disorders. If ovulation is infrequent or absent, fewer eggs are available for fertilization.

(3) Endometriosis. Endometriosis occurs when tissue similar to the lining of the uterus implants and grows outside of the uterus; often affecting the function of the ovaries, uterus and fallopian tubes.

(4) Uterine fibroids. Fibroids are benign tumors in the uterus. They are common in women in their 30s and 40s. Fibroids can interfere with implantation of the fertilized egg.

(5) Previous tubal sterilization or removal. Tubal ligation is a type of sterilization in which the fallopian tubes are cut or blocked to permanently prevent pregnancy. If you wish to conceive after tubal ligation, IVF may be an alternative to tubal ligation reversal surgery.

(6) Impaired sperm production or function. Below-average sperm concentration, weak movement of sperm (poor mobility), or abnormalities in sperm size and shape can make it difficult for sperm to fertilize an egg. If semen abnormalities are found, a visit to an infertility specialist might be needed to see if there are correctable problems or underlying health concerns.

(7) Unexplained infertility. Unexplained infertility means no cause of infertility has been found despite evaluation for common causes.

(8) A genetic disorder. If you or your partner is at risk of passing on a genetic disorder to your child, you may be candidates for pre-implantation genetic testing; a procedure that involves IVF. After the eggs are harvested and fertilized, they are screened for certain genetic problems, although not all genetic problems can be found. Embryos that do not contain identified problems can be transferred to the uterus.

(9) Fertility preservation for cancer or other health conditions. If you are about to start cancer treatment, such as radiation or chemotherapy, that could harm your fertility, IVF for fertility preservation may be an option. Women can have eggs harvested from their ovaries and frozen in an unfertilized state for later use. Or the eggs can be fertilized and frozen as embryos for future use.

RISKS OF IVF INCLUDE

(a) Multiple births. IVF increases the risk of multiple births if more than one embryo is transferred to your uterus. A pregnancy with multiple fetuses carries a higher risk of early labor and low birth weight than pregnancy with a single fetus does.

(b) Premature delivery and low birth weight. Research suggests that IVF slightly increases the risk that the baby will be born early or with a low birth weight.

(c) Ovarian hyper-stimulation syndrome. Use of injectable fertility drugs, such as human chorionic gonadotropin (HCG), to induce ovulation can cause ovarian hyper-stimulation syndrome, in which your ovaries become swollen and painful.

Symptoms typically last a week and include mild abdominal pain, bloating, nausea, vomiting and diarrhea. If you become pregnant, however, your symptoms might last several weeks. Rarely, it is possible to develop a more severe form of ovarian hyper-stimulation syndrome that can also cause rapid weight gain and shortness of breath.

(d) Miscarriage. The rate of miscarriage for women who conceive using IVF with fresh embryos is similar to that of women who conceive naturally, about 15% to 25%, but the rate increases with maternal age.

Egg-retrieval procedure complications. Use of an aspirating needle to collect eggs could possibly cause bleeding, infection or damage to the bowel, bladder or a blood vessel. Risks are also associated with sedation and general anesthesia, if used.

(e) Ectopic pregnancy. About 2% to 5% of women who use IVF will have an ectopic pregnancy. Ectopic pregnancy occurs when the fertilized egg implants outside the uterus, usually in a fallopian tube. The fertilized egg cannot survive outside the uterus, and there is no way to continue the pregnancy.

(f) Birth defects. The age of the mother is the primary risk factor in the development of birth defects, no matter how the child is conceived. More research is needed to determine whether babies conceived using IVF might be at increased risk of certain birth defects.

(g) Cancer. Although some early studies suggested there may be a link between certain medications used to stimulate egg growth and the development of a specific type of ovarian tumor, more-recent studies do not support these findings. There does not appear to be a significantly increased risk of breast, endometrial, cervical or ovarian cancer after IVF.

(h) Stress. Use of IVF can be financially, physically and emotionally draining. Support from counselors, family and friends can help you and your partner through the ups and downs of infertility treatment.

NOTE

The success rate of a clinic depends on many factors. These include ages of the patients and medical issues, as well as the treatment population and treatment approaches of the clinic. Ask for detailed information about the costs associated with each step of the procedure.

Before beginning a cycle of IVF using your own eggs and sperm, you and your partner will likely need various screenings, including:

(i) Ovarian reserve testing. To determine the quantity and quality of your eggs, your doctor might test the concentration of follicle-stimulating hormone (FSH), estradiol (estrogen) and anti-mullerian hormone in your blood during the first few days of your menstrual cycle. Test results, often used together with an ultrasound of your ovaries, can help predict how your ovaries will respond to fertility medication.

(ii) Semen analysis. If not done as part of your initial fertility evaluation, your doctor will conduct a semen analysis shortly before the start of an IVF treatment cycle.

(iii) Infectious disease screening. You and your partner will both be screened for infectious diseases, including HIV.

(iv) Practice (mock) embryo transfer. Your doctor might conduct a mock embryo transfer to determine the depth of your uterine cavity and the technique most likely to successfully place the embryos into your uterus.

(v) Uterine exam. Your doctor will examine the inside lining of the uterus before you start IVF. This might involve a sonohysterography, in which fluid is injected through the cervix into your uterus; and an ultrasound to create images of your uterine cavity. Or it might include a hysteroscopy, in which a thin, flexible, lighted telescope (hysteroscope) is inserted through your vagina and cervix into your uterus.

Before beginning a cycle of IVF, consider important questions, including:

(a) How many embryos will be transferred? The number of embryos transferred is typically based on age and number of eggs retrieved. Since the rate of implantation is lower for older women, more embryos are usually transferred, except for women using donor eggs or genetically tested embryos.

(b) Most doctors follow specific guidelines to prevent a higher order multiple pregnancy, such as triplets or more. In some countries, legislation limits the number of embryos that can be transferred. Make sure you and your doctor agree on the number of embryos that will be transferred before the transfer procedure.

(c) What will you do with any extra embryos? Extra embryos can be frozen and stored for future use for several years. Not all embryos will survive the freezing and thawing process, although most will.

(d) Having frozen embryos can make future cycles of IVF less expensive and less invasive. Or, you might be able to donate unused frozen embryos to another couple or a research facility. You might also choose to discard unused embryos.

(e) How will you handle a multiple pregnancy? If more than one embryo is transferred to your uterus, IVF can result in a multiple pregnancy, which poses health risks for you and your babies. In some cases, fetal reduction can be used to help a woman deliver fewer babies with lower health risks. Pursuing fetal reduction, however, is a major decision with ethical, emotional and psychological consequences.

(f) Have you considered the potential complications associated with using donor eggs, sperm or embryos, or a gestational carrier? A trained counselor with expertise in donor issues can help you understand the concerns, such as the legal rights of the donor. You may also need an attorney to file court papers to help you become legal parents of an implanted embryo.

THE POSSIBLE SIDE EFFECTS OF IVF DRUGS INCLUDE:

nausea and vomiting, difficulty breathing, irritability, hot flashes, enlargement of the ovaries, difficulty sleeping, abdominal pain, Ovarian hyperstimulation syndrome (OHSS).

Rarely, the medications used to stimulate ovaries to produce eggs can cause OHSS. This happens when there is an over response to the medications being used and the hormone levels become very elevated.

People with OHSS have a large number of growing follicles and high estrogen levels. This leads to fluid leaking into the abdomen, which may cause bloating, nausea, and swelling of the abdomen.

With severe OHSS, the following symptoms are possible: blood clots, shortness of breath, dehydration, vomiting and Pregnancy loss

The leading cause trusted Source of pregnancy loss, whether in IVF or natural conception, is an abnormal number of chromosomes, known as chromosomal aneuploidy.

An embryo is tested with PGT to look for aneuploidy.

Multiple births

When the uterus receives more than one embryo in the transfer, there is a higher chance of having twins, triplets, or more babies.

Pregnancies with more than one fetus can result in: preterm birth or low birth weight; double the risk of the mother to develop diabetes; significant increase in the blood pressure of the mother. The doctor may recommend that there should only be a single embryo transfer in people who have a heightened chance of having twins.

BIBLIOGRAPHY

https://www.mayoclinic.org/tests-procedures/in-vitro-fertilization/about/pac-20384716 August 18 2023

Janelle Marte. In Vitro Fertilization (IVF). February 11, 2016. Medically reviewed by Janine Kelbach. https://www.healthline.com/health/in-vitro-fertilization-ivf#complications August 19 2023

Mayo Foundation for Medical Education and Research (MFMER). 1998-2023. 

Medical Art Center 2023. In Vitro Fertilization. https://medicalartcenter.com/in-vitro-fertilisation-ivf/August 18 2023

Joseph Nordqvist. All you need to know about IVF. February 17, 2023. Medically reviewed by Sanaz Ghazal