Human reproduction today has become a major health concern. A process which was thought to be so natural and producing babies was never so difficult as it has become today. Human race is the most unfertile of all mammals and it is estimated that about 10% to 15% of women aged 15–44 are infertile and seek medical help. Why has this so private and loving process moved out of the bedrooms to Infertility Clinics & ART labs, so rapidly, is baffling and even serious as it threatens the very existence of human species. Why are couples seeking medical intervention in this once so very private part of their lives ? The reasons are many and varied and both sided; its the all potent thought to be male is now implicated as a 50% reason for infertility : The detoriating semen quality is the bane of Modern Society. The part 10 years or so have seen the drastic fall in semen quality and sperm morphology attributed to many reasons like pollution, wide spread pesticide use, chemicals, stress, smoking, alcohol, sexually transmitted diseases, contraception and above all the increased influence of estrogen on men’s life. The modern day man today lives in an environment which is a virtual sea of estrogens. Dietary fats, fashions, dairy products, soya all have increased exogenous & endogenous estrogens. The sperm count of Indian males have fallen from 60–110 million to 20 million per ml of semen, this has widely contributed to the male factor of infertility and lead to many a advances in this field.
The complex female is at 50% fault, couples are putting of start of family until they have their careers established and their nests built. Most of these are nearing 35 years before they actually start trying, by this time the fixed reserve of the female ovarian oocytes has almost run out, modern stress, P.I.D., S.T.D. multiple sex partners, contraceptives further aggravate the delicate female fertility control from hypothalamus to the vagina, consequently more women than even before are seeking diagnosis and treatment of infertility.
The origin of sexual reproduction was considered to be a solved problem some 30 years ago. “Sex was said to be good for the species” (Richard Michod) By sex he meant mating of genetic material from two individuals to produce another individual with a new combination of genes; what had love got to do with this ? Was a question debated over the years without a satisfactory answer. Single celled organisms solved their problems by cloning, the others followed the group selection theory. The humans went the wrong way & the modern stress has lead to the current 15% infertility in the human race.
On July 25th 1978 infertility was conquered when Louise Brown was born. It was the efforts of Patrick Steptoe & Robert Edwards who fiddled with the gametes for 10 long years to finally produce Louise Brown as the first IVF baby of the world.
Only two decades ago did clinicians and scientists begin to work with human gametes for the purpose of treating infertility. Interest and respect for this land mark accomplishment travelled quickly to all corners of the world, for after only 20 years, hundreds and thousands of children have been born to loving homes using IVF technology.
IVF requires a team of doctors and scientists very well versed in the human reproductive physiology and gamete biology.
The ovaries are down regulated and stimulated using pure FSH and now recombinant FSH injections to the woman to produce multiple eggs. Eggs are retrieved placed in petridishes, sperms are added and left in incubator for fertilization. Carefully periodic observations are made to observe the embryo formation, several of 4 cell – 8 cell embryos are replaced and then one hopes for implantation and development of a uncomplicated pregnancy.
The advances in the development of Media and the newer ready-made media by Medicult, Scandinavian, M3blastocyst culture media has made the process of IVF very simple. Advances in machine technology incubators, integrated laminar flows etc has also made the process more simpler and less expensive.
Advances in ultrasound, color doppler and scoring of ovarian follicles and endometrium further have simplified our understanding of implantation failures and IVF-ET and in the unreceptive uteri embryo’s can be frozen for further use.
The development of cryofreezing has lead to good, matched & tested sperm banks and embryo banks with the development of electronic freezing devices it is now possible to even freeze oocytes.
With the development of high purity drugs and recombinant FSH the problems of stimulation are today almost eliminated. The use of Gn Rh antagonists in down regulation protocols with use of pure FSH and recombinant FSH it is now possible to time the cycles and batch them together to get better results.
IVF has become an indispensable technique for treatment of infertility in humans. However the implantation rates of embryos in this treatment has been reported to be approx. 10% which is significantly lower than in normal fertile couples. In older women, especially over 35 year of age, the decline in the embryonic implantation rate accelerates markedly. Hardening of zona pellucida caused by aging is partly responsible for the decline in the embryonic implantation rate. The in vitro culture procedure for embryos also leads to hardening of ZP and presumably impairs blastocyst hatching and subsequent implantation.
Cohen et al first reported that artificial opening of ZP (assisted hatching) facilitates the hatching process of blastocyts produced by human IVF and this gave better results in > 35 year old, in those with elevated FSH and in embryos with thick ZP.
Assisted hatching can be achieved by breaching the ZP (zona opening) or by thinning the ZP (zona thinning). These can be done by several methods.
Methods for zona opening :
1. Mechanical dissection
2. Acid Tyrode’s solution
3. Laser beam
Methods for zona thinning :
1. Chemical dissolution
2. Laser beam ablation
In view of the various advantages and disadvantages of above techniques newer techniques of hatching are being developed in the form of using of piezo-micromanipulators.
The development of Micromanipulation and ICSI make certain that the propagation of the species continues in spite of the declining sperm quality. Today ICSI remains the last and often first resort for most cases of severe male infertility, successful pregnancies and live births have been reported with ICSI using ejaculated sperm, sperm retrieved from epididymis (MESA), sperm aspirated from testes (TESA), sperm obtained by electro ejaculation and more recently even late spermatids. On the horizon we have the prospects of aspirating oocytes which are immature especially from PCO ovaries, prospects of germ cell injection into a mature oocyte, culturing embryo to late Blasto cyst stage for better implantation rates.
The biggest breakthrough in reproductive science is the birth of ‘Dolly‘ the first cloned mammal by the efforts of Prof. Wilmut and what more even Dolly has produced babies to prove that she is perfectly normal.
Cloning from adult differentiated cells has now become almost a reality. How for is human cloning and will we do it ? Should we do it ? has to be answered after a big debate. But imagine no sperms will be needed for human reproduction, no sex is needed. An adult cell from some one can be taken put into a empty female oocyte and coaxed to become a totipotent cell by electrical charges to develop into an embryo and this is introduced in a prepared womb to develop into an off spring and deliver after a normal gestation.
The future is Human cloning and transgenic animals, genetic engineering, gene therapy, pre implantation genetic diagnosis and ofcourse designer babies. No longer will sperms be needed to reproduce, thats how far the advances in human reproduction have reached by the start of next millennium.
Year 2000 here we come and who said Love & Sex were needed to reproduce ?
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