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Introduction

In vitro fertilization (IVF) is now a fairly common mode of treatment used for infertility and has resulted in the birth of millions of babies every year. Initially it was first used for treating couples with tubal factor infertility. Further it was used for decreased ovarian reserve by using oocyte donation. But now infertility treatment has evolved so much so that it is used in various aspects including oocyte preservation, fertility preservation for cancer patients, genetic abnormality, HLA- typing for stem cell donation, three parenting
technique and designer babies.

There are various factors causing infertility, of which 40% accounts for both male factor and female factor each while 20% remains of unknown origin. Among female factor most common reason is ovarian followed by tubal and uterine factors.

Couple may not require IVF as the primary mode of treatment. In properly evaluated cases of certain male and female factors such as mild ovulatory dysfunction, mild low sperm count or mild motility dysfunctions, simple treatment like ovulation induction, natural trial or IUI may give them success.

Indications for IVF:

1) Tubal disease. In diseased tubal cases and in cases of tubal ligation or sterilization, this mode of treatment is more useful. In tubal damage cases either we can surgically repair the tubes and try naturally or use IUI (intrauterine insemination). In certain cases where surgery is difficult or may cause a high risk of an ectopic pregnancy, where better option in vitro techniques.

2) Diminished Ovarian Function & Age Related Infertility – In premature ovarian failure and diminished reserve aggressive treatment with IVF may be required in conjunction with techniques such as assisted laser hatching and ICSI. Donor oocyte may also be an option in certain cases.

3) Anovulation & Polycystic Ovarian Syndrome (PCOS)– For cases who do not respond to other modes of ovulation induction and requiring high doses of gonadotropin therapy, there is an excellent prognosis and less risk of multiple pregnancies.

4) Endometriosis : in cases of advanced stages of endometriosis, including the presence of large or multiple endometriomas, it is the optimal 1st line of treatment.

5) Male factor. In cases with defective sperm quality or in case of sperm have difficulty in penetrating the egg such as azoospermia, oligozoospermia, asthenozoospermia, antiserum antibody etc, in vitro fertilisation with intracytoplasmic sperm injection (ICSI) may benefit.

6) Genetic Diseases / Preimplantation Genetic Screening or Diagnosis (PGS or PGD) : PGD or PGS is useful for couples who have family history or history of previous anomalous fetus or recurrent pregnancy losses or repeated IVF failures, there is chances of one or both of the partners being carriers for the genetic disease or chromosomal abnormalities.

7) Unexplained Infertility : In cases with unidentifiable cause of infertility, where other conservative treatments have failed, ART is found to more promising.

8) Other applications in-

a) HLA-typing for stem cell donation: Revolutionay designer baby concept has come up where PGD is also being used for Alzheimer’s disease, Huntington disease and cancer predisposition. Human leukocyte antigen (HLA) matching was first used to cure a child with Fanconi’s anemia. Similar approaches are being used for acute lymphoblastic leukemia, thalassemia, and Wiscott-Aldrich.

b) Fertility preservation of cancer patients: In cancer patients requiring surgery or chemotherapy or radiotherapy, gamete freezing or embryo freezing may be offered. There are options for cryopreservation of metaphase II oocytes and germinal vesicles. Ovarian tissue cryopreservation are also being done in which ovarian cortex containing primordial follicles is cryopresreved and is later transplanted after cancer treatment. Transplantation can be heterotopic in which they are transplanted back in forearm or abdomen or it may be orthotopic in which they are placed in close proximity to the infundibulo-pelvic ligament.

c) Need for embryo donation : required in women with no eggs due to surgery, chemotherapy, or genetic causes; or with poor egg quality, previously unsuccessful IVF cycles or advanced maternal age.

d) Surrogacy : Women without a uterus ( aplasia, hypoplasia or hysterectomy) or with distorted uterus or distorted uterine cavity or women with severe medical conditions may require surrogacy.

e) Single parenting and for same sex couple: in the boundaries of legality many such people are now achieving their dream to become parents.

8) Multiple failed IUI attempts: ART is recommended usually following six failed cycles of IUI.

Demerits of ART:

1) Complications related to egg retrieval: chances of bleeding ,infection, bowel or bladder damage, injury to blood vessels. Complications related to anaesthesia and drugs used.
2) Ovarian hyperstimulation : It is a life threatening condition.GnRH agonist protocol has more chances for OHSS. Use of agonist for trigger instead of hCG, anticipation of OHSS and pre managements with different drugs available has also reduced this deadly side effect.
3) Multiple pregnancies: Incidence increased due to transfer of more than one embryo, use of Laser hatching, spontaneous splitting of embryo after transfer.

4) Premature delivery and low birth weight: chances are higher in cases of multiple pregnancies and in other associated factors of infertility.
5) Miscarriage: rate of miscarriage is same for natural conception as compared to in ART conception , which is 15-25%.
6) Sex ratio distortion: it has been seen that with use of ICSI, chances for female baby increases slightly (51.3%). And with use of blastocyst transfer there is slight increase in male baby (56.1%).
7) Ectopic pregnancies: chances of 2% to 5% of ectopic pregnancies as well as heterotopic pregnancies.
8) Stress: As the precess itself is time taking with multiple visits, multiple injections, repeated scans and investigations, uncertainty of the result, couple need proper time to time counselling along with supports from friends and family.
9) Birth defects: there is a relative risk of 1.32 for babies born with in vitro techniques as compared to normal conceptions. Septal heart defects, cleft lip, cleft palate, esophageal atresia, anorectal atresia, genital defects are among the few defects expected to increase. Long term follow-up data suggest increased incidence of hypertension, impaired fasting glucose, increase in total body fat composition, advancement of bone age, subclinical thyroid disorder, cerebral palsy neurodevelopment delay, autism, attention deficit syndrome, early adulthood clinical depression and binge drinking. There is increased risk of imprinting disorders like Prader-willi syndrome and Angolan syndrome with ICSI process.

10) Transfer of Male factor infertility to male offsprings, associated with ICSI process which has made pregnancies possible in couples with sperm defects but meanwhile increases chances of genetic transfer of such defects to fetus.

Conclusion:

In the last three decades IVF has gained lot of interest and with lot of newer technologies and research, many couples have fulfilled their dream of parenthood.

Despite technological advances, there is an intense need for evaluation of long term impact of these technologies on children born through ART. Periodic meta-analysis needs to be conducted to pool well-conducted studies which may help uncover true associations between ART and infrequent diseases, birth defects and imprinting disorders.
As ART is advancing, these technologies must be used responsibly so as not to compromise with health and well being of individuals at the cost of hustle for treatment in the race to fulfil couples wishes and for the sake of doing it as everyone is doing it and making it a money business.
Right selection, right decision and right treatment is the goal for healthy mankind.

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