Why do IVF cycles fail recurrently?

Infertility is a growing concern in the developed as well as developing countries like India. According to WHO, one in every four couples is infertile. Infertility is defined as a failure to achieve pregnancy, even after one year of frequent and unprotected sexual intercourse.

What are the causes of infertility?

In males:

  1. Low sperm count, an absence of sperm in the semen, and reduced sperm structure or motility.
  2. Obstruction is limiting the flow of sperms into the semen.

In females:

  1. Ovarian malfunction is leading to poor quality of eggs or no release of eggs.
  2. Structural abnormalities in the uterus, which prevent implantation or growth of the embryo.
  3. Blockage of fallopian tubes due to which the sperm cannot reach the egg or the fertilised egg cannot move into the uterus.
  4. Obesity can cause hormonal problems which lead to infertility.
  5. Smoking
  6. Immunologic causes that prevent the sperms from fertilising the ovum.

What is IVF?

If a couple is unable to attain pregnancy despite treatment of all apparent causes, they are referred to an assisted reproductive technology (ART) expert. One of the techniques used in ART is in vitro fertilisation (IVF), where the sperm and ovum are united outside the body in a laboratory, and the resulting embryo is introduced into the uterus via various methods. The best quality eggs are then combined with the best quality sperms in the laboratory. Out of all the embryos that are formed, the embryologist selects healthiest embryos that are transferred into the uterus.

However, not all IVF procedures result in a successful pregnancy. The success rate improves with each cycle, up to 3 cycles.

If the couple fails to conceive after 3 IVF cycles, with at least 1-2 healthy embryos being transferred every time, it is termed as Recurrent Implantation Failure (RIF).

Causes of RIF:

  1. Ovarian reserve and quality of eggs drastically reduce with increasing age.
  2. Uterine abnormalities that include anatomical malformations, fibroids, and polyps.
  3. Poor health of the uterine lining.
  4. Decreased blood supply to the uterus due to a condition called thrombophilia, where blood clots block uterine blood vessels.
  5. Autoimmune causes such as thyroid autoimmunity and the presence of antiphospholipid antibody, lupus anticoagulant (LAC), anticardiolipin antibody (ACA), and antinuclear antibody (ANA).
  6. Poor quality of sperms.
  7. Genetic abnormalities in the embryo.
  8. The inability of the embryo to hatch and implant.
  9. Ovarian hyperstimulation syndrome (OHSS) caused by drugs given during IVF.

How can we help improve the success rate of IVF?

  1. Techniques like intracytoplasmic morphologic sperm insertion (IMSI), where only high-quality sperms are selected and inserted into the ovum.
  2. Surgical treatment of uterine deformations preventing implantation of an embryo.
  3. Administration of hormones to improve the thickness and quality of uterine lining.
  4. Drugs like sildenafil, aspirin or low molecular weight heparin help improve uterine blood supply.
  5. Corticosteroids, immunoglobulins, and intra-lipid therapy for autoimmune causes of RIF.
  6. Prenatal genetic testing of embryos (PGD).
  7. Zygote Intra-Fallopian Transfer (ZIFT): Embryos are transferred into the fallopian tube on days 2-3 to mimic the physiological process. Assisted hatching of the embryo to make implantation easier.
  8. Embryo culture: Embryos that grow and survive in the laboratory till day 5 (blastocysts) have higher chances of implantation.
  9. Frozen embryo transfer (FET) in the case of OHSS allows the body to recover before transferring the embryos.

Lastly, embryo transfer needs to be stress-free and painless to promote implantation.

 

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