Making mothers born again and much delayed Nobel prize!

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Making mothers born again and much delayed Nobel prize!

Tuesday, 22 December 2020 | Dr Rajendra Kr Jha

Louis Brown, the first test tube ( in fact ‘petri dish ‘ ) baby was born at 11.47 AM on 25 th July 1978 and since then around ten million healthy babies , now many of them attaining adulthood and even mothers themselves, have been born with the help of this technique making  parents and families ever so joyed and ecstatic.

The architects of this stupendous scientific feat were, much hailed Scientists duo of Dr Robert G Edward and Dr Patrick Steptoe. However, Dr Edward alone was awarded the coveted Nobel prize in 2010 for physiology or medicine because Dr Steptoe a Gynecologist, who contributed equally had died in 1988  Ironically this was awarded after more than forty years of their seminal scientific feat  squarely due to non scientific ill understood religious considerations ! Even Dr Edward would have remained without much deserved award, had it been delayed by just  a couple of years as Nobel prize is not awarded after fifty years of its discovery !

Considering the fact that as many as 10% of couples world over remain infertile in their life time withstanding excessive psycho-social pressure ,and the fact that in the year 2018 alone almost 4% of the total births were with the help of this assisted fertilisation technique of IVF ( In Vitro Fertilisation ) ,speaks volumes about it’s importance and lasting contribution it has made to the service of mankind by paradigm shift in understanding and treatment of much misconceived and  even cursed infertility .

HOW FERTISATION TAKES PLACE?

There is finite number of primordial Graafian follicles in two ovaries of women which mature and give rise to one egg cell or oocyte every month of menstrual cycle throughout their reproductive lifespan. Ovaries alternate in shedding one Graafian follicle in each month of cycle on ovulation. The oocyte drops into the adjacent Fallopian tube (connecting duct between ovary and uterus). While oocyte is still in the Fallopian tube it meets the active healthy single swimming spermatozoon from amongst millions of them which penetrate the oocyte and thus ‘zygote ‘is formed.  To start with Ovarian follicles like any other cell in the body contain 46 chromosomes which undergo meiosis,a process by which chromosomes reduce by half, in case of human being from 46 ( 44+ XX ) to two sets of 23 ( 22+X and 22+X ) chromosomes in two stages of meiosis under the influence of appropriate  female hormone named as FSH ( Follicular Stimulating Hormone) and LH (Leutinising Hormone ) controlled by famous Pituitary gland located deep in the brain.

Male counterpart the spermatozoa, present in the sperm itself undergoes reduction division of its chromosomes from 46 to 23 , is ready to meet and fuse with the egg cell to result into male -(44 + XY )or  female (44+ XX ) zygote.  It’s at this point that sex determination takes place and male or female gender is decided once for all. The process of meiosis and subsequent zygote formation is unique and has kept the evolution intact and progressing with its varieties. Genes present on the chromosomes carry the detailed chemistry of the human being within it are exchanged between them and reorganised  to give exclusivity to each zygote which multiplies into 8 call stage called blastocyst  and get ready for implantation into the endometrium of uterus kept ready by female hormones . This zygote in blastocyst stage gets imbedded in the prepared endometrium . They further multiply and differentiate into different tissues and develop as a thriving foetus which is a precursor of human adult. This journey from ovary to uterus for the oocyte and zygote takes about 3 - 5 days during which maturation and steady development simultaneously keeps taking place . The commonest cause of infertility in females is due to defects in Fallopian tube and the related structures which obstruct the pathway of oocyte and advancing spermatozoa from uterine cavity below and not let them meet. The defect can either be acquired mostly because of infective conditions such as tuberculosis or rarely due to congenital anomalies.

Such defects can be treated occasionally by surgery but most often surgery fails . Therefore, some technique which can take care of the mature egg cell and healthy spermatozoa to fertilise outside the body was considered crucial for finding cure for the infertility.

The writer is former Professor and Head of Medicine, RIMS, Ranchi, Jharkhand.

Scientists as always looked to nature and studied some aquatic animals who are known to develop the whole process of fertilisation outside female animal body.

In 1965 Dr Edward found for the first time that female egg cell ( oocyte) can be matured outside in Petri dish in buffer solution . By 1969 Dr Edward could develop a technique which successfully allowed spermatozoa to penetrate the oocyte and develop into a Zygote but such zygotes did not multiply beyond 2 cell stage . In order to reach the crucial 8 cell stage of the zygote which alone was capable to enter the endometrium required specific hormones and he could show that when such hormones were provided in adequate amount the much required maturation could be attained.

Till 1960 , in order to get sufficient number of matured oocyte open laparotomy a difficult proposition, was required thus making it a very arduous task. Dr Patrick C Steptoe who had become famous by then for fibre - optic laparoscopic technique , was approached by Dr Edward  . With Dr Steptoe utilising his skills of pin hole surgery with added ultrasound support it was possible to pickup only few mature follicles from the ovary  very easily and that too pain free and put it into the Petri dish with buffers and mix it with the collected sperm to be fertilised under controlled conditions.

Once the zygote reached the 8 cell blastocyst stage which takes about two and half days, it was possible to implant on hormone prepared endometrium of the uterus where it stays to multiply and differentiate into a healthy embryo.

Male contribution in failed fertility is almost fifty percent and the most important cause is the inadequate number of quality sperm.

 The recent technique known as Intra Cytoplasmic Sperm Inoculation ( ICSI) needs just a single healthy mature spermatozoa (singular -  spermetazoon ) which is made to penetrate the oocyte ( egg cell) and  thus providing comprehensive solution to the much vexed problem of male infertility with very high success rate .

Dr Edward’s work on human embryonic cells in the process to perfect IVF has significantly advanced the knowledge in the field of embryonic stem cell research and regenerative medicine in addition.

When to ask for IVF Help?

Needless to say that pregnancy is natural to all human however if any healthy adult couple desirous of raising family fails to conceive in six months after the age of 35 and one year after the age of 30 ,is a candidate for consultation for infertility .

Increasing age, obesity, smoking and alcohol abuse are well known relative causes for infertility in either sex. Additionally undescended and underdeveloped testis, low male hormone - testosterone and structural defects in the duct carrying the sperm to the urethral opening are additional causes.

Females may have poly-cystic disease of ovary with irregular menstruation, endometriosis and rarely ovarian failure as cause in addition to the above mentioned common causes.  Successful solution to infertility will all above factors in mind to address the problem of infertility.

It is also prudent to caution that there has been mushroom growth of fake or poorly qualified centers offering assisted fertility services like IVF and therefore diligent search for competence is extremely important to get the real benefit of this scientific wonder.

The writer is former Professor and Head of Medicine, RIMS, Ranchi, Jharkhand.

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