Treatments

Louise Brown was the first In Vitro Fertilization (IVF) baby, and was born in England in 1978. Numerous assisted reproductive technologies have developed since 1981 when the first IVF baby was born in the United States. Infertile couples now face what is often a confusing collection of acronyms when deciding how to proceed with what may be their best possibility for their own genetic child. Understanding these technologies is important if couples are to make informed decisions regarding the applicability of different assisted reproductive technology procedures.

Graphic of a sample IVF Treatment Cycle

Testing and Selection for Assisted Reproductive Technologies

Before patients receive treatment through these assisted reproductive technologies, they typically undergo a basic infertility evaluation. The evaluation involves a series of tests, and starts with a comprehensive history and physical of both partners by a Reproductive Endocrinologist (RE). The testing involved can be arbitrarily divided into two general categories: screening and specific.

    Screening tests are necessary for both the protection of the patient and the potential child. Such tests may include HIV, Hepatitis B & C, Rubella, and others. Physicians will usually accept written reports of prior test results when it is feasible and clinically appropriate. Patients are screened for reproductive tract infections before In Vitro Fertilization (IVF) or Gamete Intra Fallopian Transfer (GIFT) procedures. This often includes testing for Chlamydia, which can cause pelvic infection and tubal damage- ranging from subtle deterioration in function to complete obstruction. Mycoplasma has been implicated, although not proven, to be associated with infertility, as well as repeated pregnancy loss. Chlamydia and Mycoplasma cultures are often obtained from both the man and the woman. Should infection be found in either, both are treated with doxycycline, a tetracycline-like antibiotic for 10 days. Many specialists also screen all patients with Chlamydia antibody titers, and should these be positive (indicating previous infection) the couple is treated with doxycycline. Some studies have found no difference in pregnancy rates between treated and untreated couples, but the treatment is simple and may be beneficial. Most programs also screen couples for the HIV virus using blood antibody tests. This testing is performed to protect the potential unborn child and the laboratory personnel who must work with the sperm and eggs. Patients are also screened for hepatitis B and C, syphilis, and in some states, HTLV-1 and HTLV-2. You can check with your nearest RE to learn which tests are required for his/her clinic.

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Diagnostic testing for women covers a broad spectrum of tests from simply charting basal body temperature, to endometrial biopsy and hormonal level analyses. To evaluate pelvic factors a hysterosalpingogram, sonohysterogram, diagnostic laparoscopy, and possibly hysteroscopy may be performed. A brief synopsis of each:

• Hysterosalpingogram (HSG): A radiology procedure in which a radio-opaque fluid is injected into the uterus and fallopian tubes and photographed via x-rays to examine tubal patency, the shape of the uterus, and any intrauterine lesions (such as polyps, fibroids, or scar tissue).
  
  
• Sonohysterogram (SHG): A noninvasive office procedure by which ultrasound is used to check the size and shape of the uterus, and to detect myomas, fibroids, and ovarian cysts.
  
  
• Diagnostic Laparoscopy: A minimally invasive or outpatient surgery in which internal pelvic and abdominal organs are examined through a telescope passed through a small incision just below the umbilicus.
  
  
• Diagnostic Hysteroscopy: A minimally invasive procedure to examine the uterus, endometrial lining, and openings into the fallopian tubes by passing a small telescope through the cervix to the inside of the uterus.

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Diagnostic testing of the male by an RE skilled in the treatment of infertile males typically includes at least two semen analyses and possibly a hamster egg penetration assay (HEPA) if the man has not sired a previous pregnancy. Semen analysis provides an average sperm count, as well as an examination of the sperm motility and morphology. While the outcomes of the HEPA test will not predict with certainty the success or failure of fertilization with the woman's eggs, the test does carry some prognostic significance for non-IVF or GIFT treatments: men with poor hamster egg penetration assays have approximately half the pregnancy rate of men with normal results. The couple's cervical factor (the ability of the sperm to pass through the cervical mucus) can be evaluated by a post-coital test (PCT) and possibly a cervical mucus penetration test. Should these tests be abnormal, then more sophisticated antiserum antibody tests such as immunobead antibody testing may occasionally be appropriate in selected patients.

Not all patients need all tests. The decision about which tests are appropriate depends on physiological, psychological, social, and financial factors which are unique for each couple.

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Treatment Procedures

In Vitro Fertilization is a process whereby eggs are removed from the ovaries with a small needle passed through the top of the vagina and combined with prepared semen in the laboratory. Upon fertilization, one or more embryos are returned via a small catheter passed through the cervix into the uterus where the embryo implants and develops. With Gamete Intra Fallopian Transfer (GIFT) the eggs are combined with washed semen inside the fallopian tubes before fertilization. The relative indications and success rates for IVF and GIFT remain somewhat unclear. Numerous papers have been written which suggest that GIFT provides a higher pregnancy rate than IVF, especially in women over 40. In 1996 the United States birth rate per oocyte retrieval as reported by the SART/CDC report at http://www.cdc.gov was 25.9% for IVF and 28.7% for GIFT. It is felt a higher success rate may occur with GIFT for the following reasons:

• The fallopian tube provides a more physiologic environment for conception and early development.
  
  
• The gametes are outside the body for a shorter period of time.
  
  
• The timing of the embryo entry into the uterine cavity is more synchronized with endometrial development.
  
  
• The general IVF patient population may have a greater occurrence of altered ovarian function secondary to tubal or other disease.

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Many investigators think, however, that the comparison between IVF and GIFT may not be valid since no large prospective randomized controlled studies comparing IVF and GIFT have been carried out, so the noted differences may well be due to different types of patient populations. Much of the decision regarding which procedure to pursue will depend on the individual laboratory's experience since the success rates of IVF and GIFT in any program are relative to each other. Where a clinic is having apparently higher success rates with GIFT, it may be that they are simply having relatively lower success rates with IVF, and vice versa. The average age, diagnostic categories, and degree of infertility of the population being treated will also influence relative success rates of IVF and GIFT. It is still not clear for which patients GIFT is more appropriate than IVF. Most clinicians agree that for significant tubal disease IVF is more appropriate. However, in the presence of known male fertility- such as previous fertilization documented in a pregnancy or during IVF- then most clinicians feel GIFT is appropriate if other conditions for GIFT are met. Where there is no proof of prior male fertility and/or any evidence of male factor infertility, IVF will provide information on the fertilizing capability of the sperm, but GIFT will not. It is important, in most cases, to evaluate the male's fertility prior to exposing the patient to GIFT. The proportion of GIFT procedures have dropped dramatically in the past few years, and now comprise only approximately 1% of all assisted reproduction technology procedures.
   

For men with very poor sperm a procedure called Intra Cytoplasmic Sperm Injection (ICSI) at the time of IVF can normalize fertilization rates. During the ICSI procedure a single sperm is injected into each egg, using a microscope for visualization, as a part of the regular IVF cycle treatment. ICSI cannot be performed without IVF- it is performed in the laboratory as part of the IVF treatment cycle. Sometimes a urologist performs a Testicular Epididymal Sperm Aspiration (TESA) to collect sperm specimens through a small testicular biopsy. Sperm can often be retrieved directly from the testicles or epididymus even in men who have no sperm at the time of ejaculation. A single sperm is then injected manually into a harvested egg via micropipettes and micromanipulation. This procedure has given new hope to men who have been previously diagnosed with male factor infertility. If ICSI treatment is unsuccessful, or if patients prefer, Donor Insemination (DI) can be attempted by cervical or intrauterine insemination with cryopreserved donor sperm specimens.

    Immunologic factor infertility is confusing to both patients and their physicians. It occurs in only 2-3% of infertile patients. Investigators differ as to whether tail, head, cervical, or serum antibodies are the most important predictors of pregnancy rates-- or whether it matters much at all. Prospective randomized controlled studies are too sparse to be able to make firm conclusions regarding the best approach. Each couple will have to make their own decisions based on discussions with their physician.

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