Journal of Reproductive Endocrinology & Infertility

Short Communication

Beginning in the early 1970s, work utilizing assisted reproductive technology (ART) to treat human infertility intensified. The credit goes to Robert Edwards and Patrick Steptoe for successfully integrating ART in human reproduction, which, in 1978, yielded the birth of the world’s first so-called “test-tube baby” Louise Brown. In fact, Edwards’ work with ART earned him the Nobel Prize in 2010. The specific form of ART that allowed Lesley Brown, the mother of Louise Brown, to conceive was termed in vitro fertilization (IVF). This medical breakthrough received so much media attention that IVF quickly became a lay term. The initial unsatisfactory outcome of IVF compelled the ART pioneers to refine the culture media and stimulation medications. Over time, IVF was perfected and led to the development of new technologies. To accommodate all the emerging reproductive techniques under one umbrella, the medical literature started collectively referring to them as assisted reproductive technologies (ART). However, IVF remained the nucleus of ART. Between 1978 and 2016, ART has undergone many new developments, and ART-based infertility treatment has become a broader and stronger discipline within this incredibly short time span [1,2].

Next to IVF, intra-cytoplasmic sperm injection (ICSI) is perhaps the second most impactful ART. When it came into practice in 1990s, initially there were lot of concerns regarding its safety; however, close surveillance of ICSI born babies alleviated these fears. Available data show no significant difference between ICSI babies and IVF babies or spontaneously conceived babies. ICSI is now a routine laboratory procedure, and experts are reluctant to call ICSI a special procedure any more [3,4].

Use of cryopreservation in medicine has been around for a long time, certainly long before the introduction of ART in reproductive medicine. However, extrapolating cryotechniques from other fields and models in human reproduction had inadequate success. The researchers involved with ART gradually refined the cryo-techniques to make them suitable for use in humans. As a consequence, verification is rapidly replacing conventional slow freezing in the ART laboratory. The implantation success of vitrified embryos is now comparable to that of fresh embryos. Verification of human sperm, egg, embryos, and gonadal tissues is now a reality and an affordable option. The improvement of cryo-technology has widened the application of ART in reproductive medicine. In addition to reducing the cost of infertility treatment and creating the flexibility to choose an appropriate conception time, it created an opportunity for requisite screening to prevent the transmission of infectious pathogens. Further, cryo-technology can now help circumvent the aging effect on an individual’s reproductive potential by cryopreserving reproductive tissues at an ideal time [5-7].

Pre-implantation genetic diagnosis (PGD) technology is another ART milestone. The application of PGD in human reproduction is expanding rapidly. The primary objective of PGD is to ascertain chromosomal normalcy of the transferred embryos so that it produces a normal pregnancy. Another benefit of PGD is sex-linked diseases are preventable because pre-implantation identification of sex of the embryos is possible. PGD also has a clear advantage over amniocentesis. Amniocentesis is done in early pregnancy to assess the quality of the implanted foetus; however, PGD determines the chromosomal normalcy of the embryos before implantation, which alleviates the need for pregnancy termination. PGD technology has led to the development of a new laboratory technique called embryo biopsy (EB). EB involves polar body biopsy in oocytes, blastomere biopsy in cleaving embryos, and trophectoderm biopsy in blastocysts. Over the years, there have been significant positive changes in PGD techniques. The PGD today is not the same as it was in 80s and 90s. In previous years, PGD utilized for aneuploidy screening was based on analysing only a few chromosomes by employing fluorescence in situ hybridization (FISH). We now know that FISH is not always reliable. PGD today utilizes more sophisticated techniques, like comparative genomic hybridization by microarray technology, single nucleotide polymorphism genotyping- karyo-mapping, and next generation sequencing. Normalcy of all 24 pairs of chromosomes can be tested simultaneously, and the test accuracy is high. Thus, PGD in 2016 has reached another level of sophistication compared to previous years and is expected to continue to improve. Recent progress in PGD hints at the widespread use of reproductive genetics in human reproduction in the future [8,9].

Despite bringing tremendous success in reproduction, ART has been blamed for increasing multiple gestation rates in the patient population. The risk of multiple gestations on obstetric outcome is well documented. ART specialists are taking this issue seriously and refining embryo selection techniques so that single embryo transfer is feasible—a solution to eliminate multiple gestation. Recently immerging time-lapse and “omics” technologies have presented brighter prospects for more precise investigation of embryo viability and implantation potential. When these technologies are standardized, embryologists will be able to select the best embryo of a cohort with certainty. The research data raises hope that time-lapse imaging and “omics” will make the single embryo transfer a reality, thus eliminating the occurrence of multiple gestations [10-14].

On-going ART research may continue to push ART ahead. The advent of stem cell research has led scientists to foresee the future prospect of generating gametes—the reality of manufacturing sperm and eggs for infertile patients. They have demonstrated substantial progress using animal models. Success has already been reported in isolating stem cells from adult rodent ovary, which can become eggs. Similarly, culture of grinded testicular tissues from laboratory animals is also showing success producing spermatozoa. The somatic cell nuclear transfer also has a promising future for treating infertility. These anticipated achievements may further reshape the current mode of infertility treatment. However, cautions about the safety and unknown impact of these innovations have been expressed. Continued scientific and clinical research will help to safely transfer these technologies to clinics in the future [2,15,16].

The future of ART is full of promise, but it faces challenges. A few ARTs, such as PGD, time-lapse, and “-omics” technologies, are anticipated to create a paradigm shift in fertility care. PGD and “-omics” are likely to expand the application of genetics in human reproduction, thus building safeguards against the spread of hereditary diseases in the population. It is also projected that time-lapse imaging and “- omics” will make single embryo transfer a reality, which will eliminate the risk of multiple gestation. The challenge will be not only to make these technologies work, but also to make them simple and affordable so infertility clinics of any capacity can adapt them for patient care. The prospect of generating gametes using stem cell technology will likely require more basic research to deepen our knowledge and understanding.

References

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