Infertility Treatment Options Part 1

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Ovulation Induction (OI) and Cycle Monitoring

As the name suggests, ovulation can be induced with the aid of medical treatment. The most common agent used is Clomiphene Citrate or Clomid®. It is a tablet administered for 5 days at the beginning of the menstrual cycle (usually day 2-6). It is a highly effective treatment - 80% of patients with anovulatory infertility will become pregnant within 6 cycles/months of treatment.

It is very important that the effectiveness of the treatment is assessed. This is done by performing a trans vaginal ultrasound on day 12 of the menstrual cycle. Some women will require higher doses of Clomid® before the ovaries will respond.

If despite increasing doses of oral ovulation induction medications, the ovaries still do not respond then treatment with low dose Gonadotrophin injections can be tried (Menopur®, Puregon®). Cycle monitoring with ultrasound is also performed on all cycles with Gonadotropin.

Risks of ovulation induction cycles include:

1. Side effects of agent used: Occasional (10%) - hot flushes, nausea, headache, bloating, breast tenderness and rarely hair loss or visual disturbances.
2. Multiple Pregnancy: With oral agents the risk of multiple pregnancy is 5-10%. Nearly all multiple gestations will be twins. (Rates are higher with usage).

If the anovulation is caused by PCOS, sometimes a better response may be obtained by using other types of oral ovulatory agents such as Tamoxifen.

Intrauterine Insemination (IUI-H)

Intra Uterine insemination involves the insertion of the male partner’s semen into the female partner’s uterus in order to improve the chances of pregnancy.

The female partner’s menstrual cycles are tracked with ultrasound scanning to optimize the correct day for insemination. Ovulation induction with clomiphene or gonadotrophin injections is usually used, especially if the woman does not have regular menstrual cycles. Once ovulation is confirmed, the male partner is asked to produce a semen sample by masturbation. The specimen is prepared so that the normal active sperm are separated into a culture media. This prepared sample is then placed high up into the woman’s uterus by means of a fine catheter.

This procedure potentially treats cervical factor female infertility. It may also be beneficial for mild male factor infertility. However, is very unlikely to be successful in more severe male factor problems.

The success rate for this procedure is 10 – 15%.

Intracytoplasmic Sperm Injection (ICSI)

In a significant number of male factor couples, conventional techniques like IVF may not be possible due to a low number of motile sperm in the ejaculate. In other couples, IVF may no longer be a useful option because previous poor fertilisation rates imply a problem with sperm function. For this group, sperm microinjection (ICSI) provides the best means of achieving pregnancy.

The ICSI technique involves the injection of a sperm through both the zona pellucida and the wall of the egg directly into the centre of the egg. The procedure requires a great deal of technical skill in the picking up of individual sperm and their individual injection into the egg without damaging the ovum. All procedures are performed under a microscope using a sophisticated micromanipulation system.

Following injection, the eggs are cultured and assessed for fertilisation in a similar way to conventional IVF. Like IVF embryos are transferred into the uterus three days later or frozen for later use.

Risks

All aspects discussed under IVF apply. It is important to remember that ICSI is a relatively new treatment, the first children having been born in 1992. However, worldwide agencies collect data on the outcome of infertility treatments. Results to date do not indicate increased rates of abnormal pregnancy, miscarriage or birth defects (congenital malformations) in ICSI children. The only exception may be an increase in sex chromosome disorders such as Klinefelter's Syndrome.

As it is becoming more apparent that many cases of male infertility are genetic it is possible that these may be transmitted to future generations by ICSI. As boys inherit their Y chromosome from their father, they may have similar fertility problems later in life.

Long term assessment such as behavioral and intellectual outcomes of children born after ICSI is still ongoing. However, a number of studies have evaluated this and have not found any impairment

Success

Fertilisation and pregnancy rates are markedly improved with ICSI in severe male factor infertility (sperm counts less than 5 million/ml) and in patients with a previous history of failed IVF. In addition, men previously considered untreatable seem to have similar success, including those with completely immotile sperm, very abnormally- shaped sperm or those where sperm must be obtained from the testicle by surgery.

There is no doubt that ICSI has allowed men to father children who would previously not have been able to do so.

Intracytoplasmic Sperm Injection Video

Additional Aspects of ART Treatment

Assisted hatching

Before an embryo can implant it must hatch out of its 'shell'.  In some cases this hatching may not occur.  Assisted hatching is a procedure where the outer layer of the embryo is thinned of the embryo is thinned or opened to facilitate hatching and therefore implantation.

In general it is used when women are over 35 or if the FSH hormone level is elevated irrespective of age.

Blastocyst Culture

Conventional IVF involves culture or incubation of embryos for three days after egg retrieval. Embryos are then transferred to the uterus to be frozen.  It is now possible with new culture media that embryos can be cultured for longer - 5-6 days.

Blastocyst culture has the following potential advantages:

• It may better coincide with the timing of implantation in nature
• It potentially allows better selection of the strongest embryo for transfer
• As fewer embryos are transferred at the blastocyst stage it may reduce the incidence of multiple pregnancy.
• It may help identify a problem if patients have a number of failed IVF attempts.

Blastocyst culture does have potential disadvantages:

• The chance of having no embryos available for transfer is higher with blastocyst culture than with standard culture (up to 25%)
• A higher than expected incidence of monozygotic twins (5%) have been reported.

CONTINUE: Infertility Treatment Options Part 2

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article courtesy the Barbados Fertility Centre