B13. Treatment of infertility (ovulation induction therapy, AIH, IVF, ICSI)

Ovulation induction therapy

Definition and epidemiology

Ovulation induction therapy is a form of medical therapy used to induce ovulation. It involves blocking the negative feedback of oestradiol on the hypothalamus, causing an increase in GnRH pulse frequency, which causes increased FSH and LH levels. This induces ovarian follicular development. There are two drugs used for this:

  • Clomiphene citrate
  • Letrozole

Clomiphene citrate is the first choice. It is used when there is no known or obvious cause or infertility, the woman is < 35 years, and everything seems to be normal. It’s a selective oestrogen receptor antagonist which blocks the effect of oestradiol on the hypothalamus. As a side effect, it can cause a thinner endometrial layer and vaginal mucosa.

Letrozole is a second choice. It’s a selective aromatase inhibitor which has fewer side effects than clomiphene citrate. It blocks the negative feedback effect of oestradiol but does not increase the oestrogen level.

Assisted reproductive technologies (ART)

Assisted reproductive technologies are used to bypass the normal mechanisms of gamete transportation.

The following people are eligible for ART:

  • Women with tubal diseases
  • Unexplained infertility
  • Endometriosis
  • Immunological causes for infertility
  • Women with premature ovarian failure
  • Male factor infertility

The most important types are artificial insemination and in vitro fertilisation.

Artificial insemination

With artificial insemination, we insert processes and concentrated motile sperm cells close to the egg, into the uterus (intrauterine insemination). This is done after a mild controlled ovarian induction therapy. This increases the likelihood of pregnancy.

  • Artificial insemination by husband (AIH)
  • Artificial insemination by donor (AID)

Regular ultrasound of the ovaries is performed to determine the optimal time for the intrauterine insemination. At the optimal time, artificial α-hCG is administered to the woman to induce ovulation.

However, the effectiveness of this method is not high and so it’s rarely preferred over IVF.

In vitro fertilisation (IVF)

In vitro fertilisation refers to fertilising the egg with sperm outside the human body, after which it is implanted into the woman. It’s a process which takes weeks.

It begins with controlled superovulation, which is the stimulation of follicular development in the ovaries so that more eggs can be retrieved. A subcutaneous injection is given daily for some time to stimulate the ovaries. The drugs used can be recombinant FSH, recombinant LH, or a combination of the two. Purified gonadotropins from menopausal women’s urine may also be used.

The woman is monitored regularly with transvaginal ultrasound, as well as oestrogen and LH measurements. At the right time, artificial α-hCG is administered to the woman to induce ovulation.

After a set amount of time after the administration of artificial α-hCG, we aspirate the follicles from the ovary guided by transvaginal ultrasound. The follicular fluid is examined with a microscope to find the egg or eggs. At the day of egg retrieval, the husband gives a semen sample.

There are two ways of fertilising the egg with the sperm at this point:

  • Conventional IVF – the sperm and egg are placed together in a culture medium. The sperms fertilise the egg on their own
  • Intracytoplasmic sperm injection (ICSI) – one sperm cell is inserted into the cytoplasm of the egg

ICSI is indicated in certain cases:

  • Severe male infertility
  • Poor quality retrieved eggs
  • Previous treatment failure with conventional IVF
  • Anti-sperm antibodies
  • Sperm acquired surgically directly from the epididymis or testis

After fertilisation, the fertilised egg must be cultured for 3 or 5 days in a special culture media. The embryo is then transferred into the uterus via a small plastic catheter through the cervix. The embryo is too small to be visible on ultrasound, but the embryo in the catheter is cleverly surrounded by two air bubbles which are visible on ultrasound, and which can be used to determine if the embryo transfer was successful.

After the embryo transfer, the luteal phase must be supported by progesterone supplements, either parenterally or intravaginally administered.

2 weeks after the embryo transfer, the patient makes a blood test to check the β-hCG level. 3 weeks after the transfer, the first transvaginal ultrasound is performed to check for the presence of a 5-week pregnancy.

Problems with IVF

  • Stress
  • Cost
  • Surgical risks
  • Higher risk for multiple pregnancy
  • Ovarian hyperstimulation syndrome (topic B14)

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B12. Infertility; classifications and diagnosis

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B14. Ovarian hyperstimulation syndrome

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