Infertility Medicine/IVF

In vitro fertilisation (IVF) is a process of fertilisation where an egg is combined with sperm outside the body, in vitro("in glass"). The process involves monitoring and stimulating a woman's ovulatory process, removing an ovum or ova (egg or eggs) from the woman's ovaries and letting sperm fertilise them in a liquid in a laboratory. The fertilised egg (zygote) undergoes embryo culture for 2–6 days, and is then transferred to the same or another woman's uterus, with the intention of establishing a successful pregnancy.

IVF may be used to overcome female infertility where it is due to problems with the fallopian tubes, making in vivo fertilisation difficult. It can also assist in male infertility, in those cases where there is a defect in sperm quality; in such situations intracytoplasmic sperm injection (ICSI) may be used, where a sperm cell is injected directly into the egg cell. This is used when sperm has difficulty penetrating the egg, and in these cases the partner's or a donor's sperm may be used. ICSI is also used when sperm numbers are very low. When indicated, the use of ICSI has been found to increase the success rates of IVF.

IVF treatment is appropriate in cases of unexplained infertility for women that have not conceived after 2 years of regular unprotected sexual intercourse.

Success rates:

IVF success rates, the percentage of all IVF procedures which result in a favourable outcome. Depending on the type of calculation used, this outcome may represent the number of confirmed pregnancies, called the pregnancy rate, or the number of live births, called the live birth rate. The success rate depends on variable factors such as maternal age, cause of infertility, embryo status, reproductive history and lifestyle factors.

Maternal age: Younger candidates of IVF are more likely to get pregnant. Women older than 41 are more likely to get pregnant with a donor egg.

Reproductive history: Women who have been previously pregnant are in many cases more successful with IVF treatments than those who have never been pregnant.

Due to advances in reproductive technology, IVF success rates are substantially higher today than they were just a few years ago.

Live birth rate:

The live birth rate is the percentage of all IVF cycles that lead to a live birth. This rate does not include miscarriage or stillbirth and multiple-order births such as twins and triplets are counted as one pregnancy.

 

<35

35-37

38-40

41-42

>42

 

Pregnancy rate

46.7

37.8

29.7

19.8

8.6

 

Live birth rate

40.7

31.3

22.2

11.8

3.9

 

IVF attempts in multiple cycles result in increased cumulative live birth rates. 40% success rate after first cycle and 90% after three cycles.

Pregnancy rate:

 

<35

35-37

38-40

41-42

Pregnancy rate

47.6

38.9

30.1

20.5

Predictors of success:

The main potential factors that influence pregnancy (and live birth) rates in IVF have been suggested to be maternal age, duration of infertility or subfertility, bFSH and number of oocytes, all reflecting ovarian function. Optimal woman's age is 23–39 years at time of treatment.

Biomarkers that affect the pregnancy chances of IVF include:
  • Antral follicle count, with higher count giving higher success rates.
  • Anti-Müllerian hormone levels, with higher levels indicating higher chances of pregnancy, as well as of live birth after IVF, even after adjusting for age.
  • Factors of semen quality for the sperm provider.
  • Level of DNA fragmentation as measured e.g. by Comet assay, advanced maternal age and semen quality.
  • Women with ovary-specific FMR1 genotypes including het-norm/low have significantly decreased pregnancy chances in IVF.
  • Progesterone elevation (PE) on the day of induction of final maturation is associated with lower pregnancy rates in IVF cycles in women undergoing ovarian stimulation using GnRH analogues and gonadotrophins. At this time, compared to a progesterone level below 0.8 ng/ml, a level between 0.8 and 1.1 ng/ml confers an odds ratio of pregnancy of approximately 0.8, and a level between 1.2 and 3.0 ng/ml confers an odds ratio of pregnancy of between 0.6 and 0.7. On the other hand, progesterone elevation does not seem to confer a decreased chance of pregnancy in frozen–thawed cycles and cycles with egg donation.
  • Characteristics of cells from the cumulus oophorus and the membrana granulosa, which are easily aspirated during oocyte retrieval. These cells are closely associated with the oocyte and share the same microenvironment, and the rate of expression of certain genes in such cells are associated with higher or lower pregnancy rate.
  • An endometrial thickness (EMT) of less than 7 mm decreases the pregnancy rate by an odds ratio of approximately 0.4 compared to an EMT of over 7 mm. However, such low thickness rarely occurs, and any routine use of this parameter is regarded as not justified.
Other determinants of outcome of IVF include:
  • Tobacco smoking reduces the chances of IVF producing a live birth by 34% and increases the risk of an IVF pregnancy miscarrying by 30%.
  • A body mass index (BMI) over 27 causes a 33% decrease in likelihood to have a live birth after the first cycle of IVF, compared to those with a BMI between 20 and 27. Also, pregnant women who are obese have higher rates of miscarriage, gestational diabetes, hypertension, thromboembolism and problems during delivery, as well as leading to an increased risk of fetal congenital abnormality. Ideal body mass index is 19–30.
  • Salpingectomy or laparoscopic tubal occlusion before IVF treatment increases chances for women with hydrosalpinges.
  • Success with previous pregnancy and/or live birth increases chances
  • Low alcohol/caffeine intake increases success rate
  • The number of embryos transferred in the treatment cycle
  • Embryo quality
  • Some studies also suggest the autoimmune disease may also play a role in decreasing IVF success rates by interfering with proper implantation of the embryo after transfer.

Method:

Theoretically, IVF could be performed by collecting the contents from a woman's fallopian tubes or uterus after natural ovulation, mixing it with sperm, and reinserting the fertilised ova into the uterus. However, without additional techniques, the chances of pregnancy would be extremely small. The additional techniques that are routinely used in IVF include ovarian hyperstimulation to generate multiple eggs or ultrasound-guided transvaginal oocyte retrieval directly from the ovaries; after which the ova and sperm are prepared, as well as culture and selection of resultant embryos before embryo transfer into a uterus.