In vitro fertilization (IVF) is a technique of assisted reproduction whereby a zygote is produced from the fertilization of sperm and oocytes outside the woman’s body, and allowed to proceed in its development under carefully controlled conditions, until it becomes an embryo.
Thereafter it is transferred into the uterus, either by inserting it into the Fallopian tubes, but more recently by intra-vaginal placement into the uterus. If the embryo implants, a pregnancy has begun. If the pregnancy results in the birth of a live infant who is capable of surviving outside the mother’s body, a successful IVF cycle has taken place.
Modern technology and advances in knowledge of the reproductive parameters is leading to increased success in both the pregnancy rates and live birth rates following IVF. However, the procedure is accompanied by risks.
General risks
IVF is a reproductive option which requires intensive hormonal treatments that can cause many medical complications i.e. it is physically strenuous.
The emotional strain is no less because the results of the intervention are far from certain. This is exacerbated by the multi-stage nature of the process, which means the couple has to wait to see if the current phase has worked before they can proceed to the next, with some stages requires repetition until successful.
The time spent off work undergoing and recovering from the treatments is far from negligible, and there is considerable expense associated with this technology. Many insurance companies do not offer plans which cover infertility treatment, with the fees for a single IVF treatment cycle crossing $10,000 to $20,000. This includes the costs of the fertility hormones, laparoscopy and ultrasounds, anesthesia, the repeated blood tests for hormone levels, oocyte and sperm processing, storage, embryo storage and embryo transfer.
Since couples who opt for IVF are already handling the difficulty of infertility, these added strains can well precipitate stress and depression. The disappointment of a failed cycle on top of immense investments in the shape of time, money, and energy may deepen the impact of other stressors.
Ovarian stimulation
The adverse effects of many fertility hormones include abdominal or generalized bloating, abdominal pain, fluctuations in emotional states, and headaches. Many of them are administered by repeated injections, which can cause bruising besides being painful.
An uncommon but serious complication of ovarian stimulation treatment, which is the first stage of IVF, is ovarian hyperstimulation syndrome (OHSS). This is due to the accumulation of edema fluid within the chest and the abdomen. As a result, the abdomen may swell and hurt, the patient may bloat up, and they may report rapid increases in weight within a couple of days.
Their urine output may decrease because of extravascular sequestration of body water, despite an adequate fluid intake. Dyspnea, nausea and vomiting are other features. While mild OHSS can be managed by promptly stopping the cycle and complete rest, in severe cases intensive management, including paracentesis to relieve ascites, may be indicated.
While some fears exist that the use of fertility hormones is linked to cancer, no evidence has ever been produced.
Oocyte retrieval
Ovarian stimulation is performed to enable multiple oocytes to be produced, which have to be retrieved by ultrasound-guided transvaginal follicular aspiration of both ovaries. This is accompanied by its own risks, though uncommon, such as:
- Reactions to the anesthetic agent used
- Bleeding from the needle track
- Infection
- Damage to surrounding structures, including the bladder and bowel
Embryo transfer
In general, more than one embryo is transferred into the uterus of the woman undergoing IVF – this is to maximize the chances of a successful pregnancy. While this is useful in preventing many repeated cycles, placing more than two embryos into the uterus increases the chances of multiple pregnancy, which is found to occur in almost half of pregnancies induced by IVF.
Multiple pregnancy increases the risk to both the mother and baby. The mother has a higher risk of pregnancy-induced hypertension, hydramnios, preterm labor, and complicated delivery. Additionally, the fetus may suffer from a higher risk of congenital malformations, premature birth, low birth weight, and the need for intensive neonatal care.
Pregnancy
If a pregnancy test is positive two weeks after embryo transfer is done, the woman is deemed pregnant. She is usually put on daily progesterone supplements from the day of transfer until the implantation is confirmed to be successful and until the first trimester of pregnancy is over. Progesterone is a hormone that makes the endometrium thicker and more vascular, preparing it for implantation of the embryo.
Complications of pregnancy have been reported following IVF, such as:
| Pregnancy complication |
Reported frequency (%) |
| Ectopic pregnancy |
2 |
| Miscarriage |
21 |
| Multiple pregnancy |
28 |
| Pregnancy-induced hypertension |
10 |
| Preterm labor |
22 |
| Intrauterine death |
10 |
Perinatal outcomes
Perinatal outcomes are significantly worse for children conceived by ICSI or IVF compared to natural conception.
Intracytoplasmic sperm injection (ICSI) has become part of the IVF protocol, allowing even azoospermic, asthenospermic, and teratozoospermic men to father children. However, it is not yet known how this artificial method of fertilization affects the natural process of sperm selection. It is possible that ICSI overcomes natural barriers to conception caused by genetically transmissible causes of male infertility.
Such barriers may include chromosomal anomalies, mutations in the cystic fibrosis transmembrane conductance regulator gene, or AZF deletions, all of which would normally not be transmitted to offspring because they were not conducive to conception. One study found that the incidence of new chromosomal aberrations in ICSI-derived pregnancies when the sperm count was extremely low (below 20 million per ml) was 10 times higher than that in ICSI-pregnancies using sperm from men with sperm counts higher than this level. Again, researchers have found that the rate of major congenital defects is doubled in ICSI or IVF pregnancies.
Another area of concern is the damage to cell organelles potentially caused by ICSI, which may cause congenital defects. Imprinting disorders are also found to increase in incidence in IVF pregnancies. It is postulated that the teratogenic influence may be the embryo culture medium rather than the use of ICSI, in these cases. Again, it is possible that the same mechanism underlay both infertility and the imprinting defect.
Children conceived by IVF techniques also have a tendency to be low birth weight and have higher fasting blood sugar and blood pressure levels than normally conceived children. Even singletons born after IVF tend to be at risk for preterm birth. They also have worse outcomes before, during, and after birth, and are more likely to require hospitalization.
Cerebral palsy, psychological diseases, and developmental delays, are more common in these infants than in naturally conceived children.
References
- https://www.betterhealth.vic.gov.au
- https://www.hfea.gov.uk/treatments/explore-all-treatments/risks-of-fertility-treatment/
- https://medlineplus.gov/ency/article/007279.htm
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1936357/
- https://www.ncbi.nlm.nih.gov/pubmed/24365026
- https://www.ncbi.nlm.nih.gov/pubmed/17079550
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3114573/
Further Reading
Association between infertility and autism spectrum disorder risk among children