Standard ART techniques

In-vitro fertilization – embryo transfer (IVF-ET)

What it means?
IVF stands for in-vitro-fertilization and ET for embryo transfer. It actually means fertilization i.e. meeting of eggs and sperms outside the female body in the IVF laboratory. The embryo which is thus formed is put back into the womb. Popularly known as test tube baby.

Who are suitable candidates?
Almost any condition which is leading to infertility can be helped by IVF.

  • 1. Bilateral blocked or absent tubes
  • 2. Endometriosis
  • 3. Unexplained infertility
  • 4. Genital tuberculosis
  • 5. Moderate male factor
  • 6. Failed IUI
  • 7. PCOD failed ovulation induction
  • 8. Prolonged infertility
  • 9. Time short
  • 10. Advancing maternal age

 
Who should not get IVF-ET?

  • Very short infertility
  • Contraindications to pregnancy
  • Poor endometrial cavity or lining
  • Badly distorted uterus
  • Poor ovarian reserve
  • Big hydrosalpinx
  • Big fibroids
  • Active pelvic infection

 
What are its main steps?

  • Step-1 Complete workup for general fitness and assessment of ovarian and uterine function
  • Step-2 Giving injections to knock out control of the menstrual cycle by pituitary and higher centres. This can be achieved by two protocols. In long protocol injections known as GnRH-agonists are started few days before menses. In short protocol these are added after the follicles start developing. Both these protocols have their own role, advantages and disadvantages.
  • Step-3 Hormone injections are started with the onset of menses as to achieve 10-12 follicles. The growth is monitored with the help of ultrasound and blood hormone tests. Final maturation trigger is given once at least three lead follicles are more than 16-17 mm diameter.
  • Step-4 Ovum pick-up (OPU) is done 36 hours after final maturation trigger. It is a short procedure done under short general anaesthesia. Eggs are removed from ovaries under ultrasound guidance with the help of a needle mounted on trans-vaginal ultrasound probe. There are no cuts or stitches. There is no intra or post op pain.
  • Step-5 Semen is taken from male partner and processed in laboratory to take out best sperms.
  • Step-6 Eggs are mixed with sperms in culture dish. Sperms enter the eggs with their own power.
  • Step-7 Development of the fertilized eggs (now called embryos) is checked
  • Step-8 Embryo transfer is done at 48-72 hours when embryo is at 4-8 cell stage.
  • Step-9 Medicines are given to support the possible pregnancy
  • Step-10 Blood test for pregnancy is done 12 days after ET to confirm pregnancy.

 
Advantages:

  • It is a highly effective technique. Success rates per cycle are in the range of 40-45 %. Although costly but this is the most cost effective technique available.

 
Disadvantages:

  • Cost, time (nearly 6 weeks total) and success rate less than 50%. Generally very safe but serious side effects like OHSS etc. and multiple pregnancy can occur.

 
Legal status:

  • Allowed by the Indian Council of Medical Research guidelines, when done with the consent of both partners. The child thus born has all legal rights and obligations. The female partner should be above the age of 21 years.

Intracytoplasmic sperm injection (ICSI)

What it means?
ICSI stands for intracytoplasmic sperm injection. It actually means injecting single sperm in every egg one by one with the help of a very fine equipment called micromanipulator. It is an additional procedure to IVF.

Who are suitable candidates?

  • Primary indication is severe decreased sperm count or motility.
  • Unexplained infertility
  • Almost any condition where IVF is being done ICSI can be done

 
Who should not get ICSI?
There are no specific contraindications for ICSI in a couple going for IVF-ET.

What are its main steps?
Steps are same as for IVF-ET except that for the lab procedure of insemination of eggs.

  • Step-1 Complete workup for general fitness and assessment of ovarian and uterine function
  • Step-2 Giving injections to knock out control of the menstrual cycle by pituitary and higher centres. This can be achieved by two protocols. In long protocol injections known as GnRH-agonists are started few days before menses. In short protocol these are added after the follicles start developing. Both these protocols have their own role, advantages and disadvantages.
  • Step-3 Hormone injections are started with the onset of menses as to achieve 10-12 follicles. The growth is monitored with the help of ultrasound and blood hormone tests. Final maturation trigger is given once at least three lead follicles are more than 16-17 mm diameter.
  • Step-4 Ovum pick-up (OPU) is done 36 hours after final maturation trigger. It is a short procedure done under short general anaesthesia. Eggs are removed from ovaries under ultrasound guidance with the help of a needle mounted on trans-vaginal ultrasound probe. There are no cuts or stitches. There is no intra or post op pain.
  • Step-5 Semen is taken from male partner and processed in laboratory to take out best sperms.
  • Step-6 Eggs are mixed with sperms in culture dish. Sperms enter the eggs with their own power.
  • Step-7 Development of the fertilized eggs (now called embryos) is checked
  • Step-8 Embryo transfer is done at 48-72 hours when embryo is at 4-8 cell stage.
  • Step-9 medicines are given to support the possible pregnancy
  • Step-10 Blood test for pregnancy is done 12 days after ET to confirm pregnancy.

 
Advantages:

  • It is a highly effective technique. Success rates per cycle are in the range of 40-45 %. Although costly but this is the most cost effective technique available.

 
Disadvantages:

  • Cost, time (nearly 6 weeks total) and success rate less than 50%. Generally very safe but serious side effects like OHSS etc. and multiple pregnancy can occur.

 
Legal status:

  • Allowed by Indian Council of Medical Research guidelines, when done with the consent of both partners.
  • The child thus born has all legal rights and obligations. The female partner should be above the age of 21 years.

ICSI with Testicular sperm (TESA/TESE/Micro TESE/PESA)

What it means?
ICSI stands for intracytoplasmic sperm injection. It actually means injecting single sperm in every egg one by one with the help of a very fine equipment called micromanipulator. It is an additional procedure to IVF. When ICSI is done with sperms taken directly from testis it is called ICSI with testicular sperm. TESA/TESE/Micro TESE/PESA are various techniques for obtaining sperms from testis. The choice depends upon the indication of obtaining testicular sperms directly from the testis. PESA and micro TESE are the most commonly performed techniques.
TESA – testicular sperm aspiration
TESE – testicular sperm extraction
Micro-TESE – retrieval of best sperms from healthy tubules of testes under operating microscope
PESA – percutaneous epididymal sperm aspiration
 
Who are suitable candidates?

  • Primary indication is azoospermia or absent sperm in semen
  • Severe decreased sperm count or motility, sometimes testicular sperm give better result
  • Blockage of vas or ejaculatory ducts (the male ducts)
  • Spinal injury, severe sexual dysfunction, retrograde ejaculation. Anejaculation
  • High DNA fragmentation in semen

 
Who should not get ICSI –with testicular sperm?

  • Very High FSH
  • High surgical risk, e.g. very high BP, uncontrolled diabetes heart disease etc.
  • Men with genetic abnormalities

 
Is FNAC required to decide?

  • No. Spermatogenesis in testes can be patchy and FNAC can give information on the area sampled
  • Can Patients with Sertoli cell only, or testicular atrophy on FNAC try testicular sperm?
  • Yes, there is nearly 50 % chance of getting functional sperms even in these cases
  •  
    How much rest is required?

    • Not much. Only cases of micro-TESE may require a few days’ rest.

     
    What are its main steps?
    Steps are same as for IVF-ET and ICSI. In addition procedures for sperm retrieval and isolation are required.

    • Step-1 Complete workup for both partners for general fitness and assessment of ovarian and uterine function. The male partner needs to be thoroughly examined and counselled for selection of procedure and anaesthesia.
    • Step-2 Giving injections to knock out the control of menstrual cycle by pituitary and higher centres. This can be achieved by two protocols. In long protocol injections known as GnRH-agonists are started few days before menses. In short protocol these are added after the follicles start developing. Both these protocols have their own role, advantages and disadvantages.
    • Step-3 Hormone injections are started with the onset of menses as to achieve 10-12 follicles. The growth is monitored with the help of ultrasound and blood hormone tests. Final maturation trigger is given once at least three lead follicles are more than 16-17 mm diameter.
    • Step-4 Ovum pick-up (OPU) is done 36 hours after final maturation trigger. It is a short procedure done under short general anaesthesia. Eggs are removed from ovaries under ultrasound guidance with the help of a needle mounted on trans-vaginal ultrasound probe. There are no cuts or stitches. There is no intra or post op pain.
    • Step-5 Spermatozoa are taken out from testes by the surgeon and isolated in the IVF laboratory to take out the best sperms. Except for micro-TESE all other procedures can be done under local anaesthesia. For micro-TESE spinal or general anaesthesia is required.
    • Step-6Eggs are injected with sperms isolated from testicular aspirate. Isolation of sperms is a highly technical and specialized procedure and takes almost 2-3 hours.
    • Step-7 Development of the fertilized eggs now called embryos is checked every day.
    • Step-8 Embryo transfer is done when at 48-72 hours when embryo is at 4-8 cell stage.
    • Step-9 Medicines are given to support the possible pregnancy.
    • Step-10 Blood test for pregnancy is done 12 days after ET to confirm pregnancy.

     
    Advantages:

    • It is a highly effective technique. Success rates per cycle are in the range of 40-45 %. In young couples success is even higher. Although costly but this is the only technique which gives the men suffering from azoospermia or very poor sperm counts a chance to get their own biological child. The only other option is adoption.

     
    Disadvantages:

    • The procedure costs nearly 35 to 40 thousand rupees over and above the cost of IVF. Generally there are no complications but rare cases of bleeding and pain may be there.

     
    Legal status:

    • Since the child is genetically linked to the male partner there are no legal issues involved.

     


    IVF with OD

    What it means?
    IVF stands for in-vitro-fertilization and ET for embryo transfer. It actually means fertilization i.e. meeting of eggs and sperms outside the female body in the IVF laboratory. The embryo which is thus formed is put back into the womb. Popularly known as test tube baby. When eggs are taken from another women it is called IVF withovum donation or briefly IVF with OD.

    Who are suitable candidates?
    When the women’s ability to produce good quality eggs ovum donation is required.

    • Age related decline in fertility. Nearly 10-13 years before menopause ( stoppage of menses) ovaries get weak. They keep on ovulating and bringing hormonal changes adequate for menstruation. But the quantity and quality of eggs is severely compromised.
    • Postmenopausal women
    • premature ovarian failure
    • ovaries absent by birth
    • unexplained fertilization failure or implantation failure.
    • Carriers of genetic diseases especially sex linked inherited diseases.
    • serious medical illness contraindicating egg retrieval
    • unapproachable ovaries due to previous surgeries, endometriosis etc
    • surgically removed ovaries
    • Gay couples

     
    Who should not get IVF-ET with OD?

    • Poor endometrial cavity or lining
    • Badly distorted uterus
    • Big hydrosalpinx
    • Big fibroids
    • Active pelvic infection

     
    What are its main steps?

    • Step-1 complete workup for both partners for general fitness and assessment of ovarian and uterine function
    • Step-2 selection and detailed assessment of donor
    • Step-3 synchronization of menstruation of donor and recipient
    • Step-4 stimulation of ovaries of donors. This involves giving injections to knock out the control of menstrual cycle by pituitary and higher centres. This can be achieved by two protocols. In long protocol injections known as GnRH-agonists are started few days before menses. In short protocol these are added after the follicles start developing. Both these protocols have their own role, advantages and disadvantages.
      The recipient is also given Medicines to control her cycle.
    • Step-5 the donor is started with hormone injections with the onset of menses as to achieve 10-12 follicles. The growth is monitored with the help of ultrasound and blood hormone tests. Final maturation trigger is given once at least three lead follicles are more than 16-17 mm diameter.
      Simultaneously recipient is also given hormones to build the lining of uterus or endometrium.

    • Step-6 Ovum pick-up (OPU) of donor is done 36 hours after final maturation trigger. It is a short procedure done under short general anaesthesia . Eggs are removed from ovaries under ultrasound guidance with the help of a needle mounted on trans-vaginal ultrasound probe. There are no cuts or stitches.There is no intra or post op pain.
    • Step-7 Semen is taken from male partner and processed in laboratory to take out best sperms.
    • Step-8 Eggs are inseminated with sperms in culture dish.
    • Step-9 Development of the fertilized eggs now called embryos are checked
    • Step-10 Embryo transfer is done when at 48-72 hours when embryo is at 4-8 cell stage.
    • Step-11 medicines are given to support the possible pregnancy to recipient. No more medicines are given to donor.
    • Step-12 Blood test for pregnancy is done 12 days after ET to confirm pregnancy.

      
    Advantages:

    • It is a highly effective technique. Success rates per cycle are in the range of 40-45 %. Although additional cost of arranging donor is there but this is the only method with which a women can carry her husband’s sperm in her own uterus. Only other option is adoption.

     
    Disadvantages:

    • Additional cost. Waiting list because of shortage of donors.Generally very safe. In older women especially who have medical problems hormones and pregnancy have higher risks.

     
    Legal status:

    • Allowed by Indian Council of medical research guidelines when done with the consent of both partners. The child thus born has all legal rights and obligations. Donation from known donors or relations is not allowed.

    Assisted Hatching

    What it means?
    There is a protective shell outside the egg and embryo. The embryo comes out of it before implantation. This process is called hatching. When this procedure is done artificially it is called assisted hatching. Basically means making a hole in zonapellucida.

    Who are suitable candidates?

    • Recurrent implantation failure
    • After cryofreezing
    • before trophoectoderm biopsy (blastocyst biopsy)
    • thick zona
    • highly fragmented embryos

     
    Who should not get embryo-cryofreezing?
    There is no role of routine assisted hatching in all cases . It improves implantation only in selected cases.
     
    What are its main steps?

    • Step-1 Embryos are selected
    • Step-2 Consent from both partners is taken
    • Step-3 A hole is made in the zona with the help of laser, sharp needle or acid tyrode.
    • Step-4 Embryos are further cultured or transferred to uterus.

     
    Advantages:

    • It is a moderately effective technique. In well selected cases it improves implantation.

     
    Disadvantages:

    • Additional cost.

     
    Legal status:

    • It is a laboratory procedure and there are no restrictions.

    Blastocyst Culture and Transfer

    Blastocyst Culture and Transfer is a technique in which an embryo is developed in the laboratory for 4-6 days after fertilization before being placed in womb. The embryo gains many cells as a result of being developed for so many days. The embryos developed for 4-6 days are much more advanced than the ones developed for just three days. These Embryos are called blastocysts.

    The embryos which survive for 4-6 days are more likely to produce the fruitful results. This enables embryologists to select from the more advanced embryos with better potential for implantation.

    The biggest advantage of Blastocyst Culture and Transfer method is that it significantly reduces the risk of multiple pregnancies. Also, the pregnancy and implantation success rate is higher in this technique because it is easy to determine the robust embryos after developing for 4-6 days hence only the competent embryo are transferred to uterus.

    With the advent of cutting-edge technology, it has become a feasible option to perform ‘minimally invasive’ surgeries with precision and finesse. Laparoscopy and Hysteroscopy are two such surgeries used to diagnose and cure certain female infertility conditions.

    Laparoscopy: It is done using a small but significant telescope named ‘Laparoscope’ to which a light source and camera are attached. It enables doctors to see ovaries, outside of uterus and fallopian tubes inside the abdomen. The doctors can perform surgeries while looking inside the abdomen. Laparoscopy is done to determine the causes of infertility, symptoms like pelvic pain & abdominal pain and to check if there are any scar tissues or blockage in the fallopian tubes. The doctors use this technique to treat cysts, endometriosis and fibroids.


    Embryo transfer

    What it means?
    ET or embryo transfer means the transfer of fertilized and cultured embryo into the woman’s uterus under ultrasound guidance.

    Who are suitable candidates?

    • Any patient who has undergone IVF for formation of embryos (fresh cycle) or has cryopreserved embryos from previous cycle (frozen embryo transfer).
    • Patient may also undergo embryo transfer of donor embryo in case the couple’s gametes (both sperm and egg) are defective. These donor embryos may be frozen or from fresh cycle.

     
    Who should not get ET?

    • Women who do not have suitable uterus for implantation eg thin endometrium, uterine adhesions etc.

     
    What are its main steps?

    • Development of the embryos is checked
    • Embryo transfer is done 48-72 hours after OPU when embryo is at 4-8 cell stage, under ultrasound guidance
    • Medicines are given to support the possible pregnancy
    • Blood test for pregnancy is done 12 days after ET to confirm pregnancy

     
    Advantages:

    • It is a highly effective technique. Success rates per cycle are in the range of 40-45 %.

     
    Disadvantages:

    • high cost, being part of IVF cycle

     
    Legal status:

    • Allowed by Indian Council of medical research guidelines when done with the consent of both partners. The child thus born has all legal rights and obligations. The female partner should be above the age of 21 years.

    Surrogacy

    What it means?
    IVF stands for in-vitro-fertilization and ET for embryo transfer. It actually means fertilization i.e. meeting of eggs and sperms outside the female body in the IVF laboratory. The embryo which is thus formed is put back into the womb. Popularly known as test tube baby. When embryos are implanted in another women’s uterus (womb) then it is called surrogacy. The baby grows for nine months in surrogate’s uterus but it is genetically linked to the couple who commissioned the surrogate.

    Who are suitable candidates?
    When the women’s uterus is absent, badly damaged or women has risk carrying pregnancy to term then surrogacy is required.
     

    • women after hysterectomy who have functioning ovaries
    • women have absent uterus by birth but have ovaries
    • Badly damaged uterus due to TB, adenomyosisetc
    • Repeated abortions due to weak uterus or cervical incompetence.
    • Serious medical illness in female partner where carrying pregnancy may be dangerous for her or baby.
    • unexplained recurrent implantation failure.
    • Gay couples and transsexuals

     
    Who should not get IVF-ET with surrogacy?

    • implantation failure due to poor eggs
    • women demanding surrogacy for social reasonsPoor endometrial cavity or lining

     
    What are its main steps?

    • Step-1 complete workup for both partners for general fitness and assessment of ovarian and uterine function
    • Step-2 selection and detailed assessment of surrogate
    • Step-3 detailed contracts and consents according to ICMR guidelines
    • Step-4 synchronization of menstruation of donor and recipient
    • Step-5 stimulation of ovaries of female partner. This involves giving injections to knock out the control of menstrual cycle by pituitary and higher centres. This can be achieved by two protocols. In long protocol injections known as GnRH-agonists are started few days before menses. In short protocol these are added after the follicles start developing. Both these protocols have their own role, advantages and disadvantages.
      The surrogate is also given Medicines to control her cycle.
    • Step-6 the female partner is started with hormone injections with the onset of menses as to achieve 10-12 follicles. The growth is monitored with the help of ultrasound and blood hormone tests. Final maturation trigger is given once at least three lead follicles are more than 16-17 mm diameter.
      Simultaneously surrogate is also given hormones to build the lining of uterus or endometrium.
    • Step-7 Ovum pick-up (OPU) of female partner is done 36 hours after final maturation trigger. It is a short procedure done under short general anaesthesia . Eggs are removed from ovaries under ultrasound guidance with the help of a needle mounted on trans-vaginal ultrasound probe. There are no cuts or stitches.There is no intra or post op pain.
    • Step-8 Semen is taken from male partner and processed in laboratory to take out best sperms.
    • Step-9 Eggs are inseminated with husbands sperms in culture dish.
    • Step-10 Development of the fertilized eggs now called embryos are checked
    • Step-11 Embryo transfer is done when at 48-72 hours when embryo is at 4-8 cell stage in surrogates uterus
    • Step-12 medicines are given to support the possible pregnancy to surrogate. No more medicines are given to female partner.
    • Step-13 Blood test for pregnancy is done 12 days after ET on surrogate to confirm pregnancy

     
    Advantages:

    • It is a highly effective technique. Success rates per cycle are in the range of 40-45 %. Although additional cost of arranging surrogate is there but this is the only method with which a couple can have their own genetic baby even in the absence of uterus. Only other option is adoption.

     
    Disadvantages:

    • Very high additional cost. Waiting list because of shortage of surrogates. Generally very safe.

     
    Legal status:

    • Allowed by Indian Council of medical research guidelines when done with the consent of both partners. The child thus born has all legal rights and obligations. Surrogacy is allowed only for Indian couples married for at least two years.