Assisted reproductive technology after the birth of Louise Brown. (2024)

Introduction

The beginning of in vitro fertilization (IVF) was an inspiringevent. Lesley Brown and her husband John, from Bristol city in theUnited Kingdom had failed to conceive naturally throughout nine years oftheir continuous marriage. Lesley Brown had bilateral tubal blocks.Bilateral salpingostomy was done without success. In 1976, she wasreferred to Dr. Patrick Christopher Steptoe, a gynaecologist in theOldham general hospital, Manchester city, United Kingdom. He advised herto try a new experimental technique to bypass her tubal blockage.Accordingly, Lesley underwent a laparoscopic oocyte retrieval during anatural non- stimulated ovulatory cycle. Mr. Robert Geoffrey Edwards, aBritish physiologist, used her husband's sperm to fertilize theretrieved oocyte in the lab. A few days later, an 8-cell stage embryowas placed inside Lesley's uterine cavity. At 11.47 PM on July 25th1978, Louise Brown was delivered by an elective caesarean section atOldham hospital by the registrar John Webster at gestational age of 38weeks and 5 days due to coincidence of maternal pre-eclampsia. Louisewas healthy at birth and her weight was 5 pounds and 12 ounces (2700grams). By the birth of Louise Brown, the world celebrated the start ofa new era of assisted human reproductive technology.

Early attempts: The history of IVF dates back as early as the1890's when Walter Heape, a professor at the University ofCambridge, UK, reported the first known case of embryo transplantationin rabbits. In 1932, Aldous Huxley described the technique of IVF in hisscience fiction novel "Brave New World". In 1934, GregoryPincus mixed rabbit's eggs and sperm in the glass top of his watchand implanted the developing embryo in a surrogate rabbit. Fourteenyears later, in 1948, Miriam Menken and John Rock retrieved more than800 oocytes from women. However, it was not until 1959 that Min ChuehChang, a young Chinese reproductive investigator, obtained indubitableevidence of in vitro fertilization by achieving live births for thefirst time from a white rabbit by using eggs and sperm from black ones.

[FIGURE 1 OMITTED]

The first human IVF pregnancy was in 1973 reported by professorsCarl Wood and John Leeton in Melbourne, Australia. Unfortunately, itended in an early embryo death (less than one week) (1). In 1976,Patrick Steptoe and Robert Edwards published a report on an ectopicpregnancy following a transfer of a human embryo at its late morulastage (2).

ART Progress: The birth of Louise Brown on July 25th 1978 (3) wasfollowed by the birth of Courtney Cross on October 16th 1978 andAlastair MacDonald on January 14th 1979, the world's first threeIVF babies. Since then, IVF has become a common procedure with a recordof more than 5 million births worldwide. The years followed have broughtrapid progress that allows more infertile couples to have their owngenetic babies (4).

Back to the year 1978 (Figure 1), Alex Lopata, in Melboure,Australia described the first ovarian cycles stimulated by clomiphenecitrate (5).

In 1979, Alastair MacDonald, the world's third IVF baby (alsoconsidered as the world's first IVF male baby) was born on January14th. Pez and his colleagues in France started tracing the growth of thegraffian follicles by using pelvic ultrasonography (6). Theirsonographic findings were correlated with the laparoscopic observations.They further indicated that the diameter of the graffian follicles, asmeasured by ultrasound, is a better predictor of follicular maturationrelative to the serum Oestradiol levels alone (on day 8th of the cycleE2 level should be [greater than or equal to] 300 pg). In 1980, theMelbourne IVF team led by Alan Trounson succeeded to deliver theAustralia's first IVF baby (the world's fourth IVF baby) afemale called Candice Elizabeth Reed (7). In the same year, the firstAmerican IVF clinic was opened in Virginia, United States (6). WHOpublished the "Laboratory manual for the examination of human sem*nand sem*n-cervical mucus interaction" to standardize sem*n analysis(8). Alan Handyside, in the United Kingdom, introduced PreimplantationGenetic Diagnosis (PGD) to identify genetically abnormal embryos by cellbiopsy (8).

In 1981, Howard and Georgianna Jones announced the delivery of thefirst American IVF baby, Elizabeth Jordan Carr in Virginia after ovarianstimulation by human menopausal gonadotrophin (hMG), (6) while SamanthaSteel was the first IVF baby born to American parents in England on thesame year. Clomiphene Citrate (CC) and human menopausal gonadotrophin(hMG) were introduced in the IVF treatment protocols by Alan Trounsonand John Leeton in Australia (9). In stimulated ovarian cycles, thenumber of mature oocytes retrieved increased and by the administrationof human chorionic gonadotrophin (hCG) identification of the exacttiming of ovulation ([+ or -] 36 hours later) and oocyte collection wasattained. Moreover, Alan Trounson noticed that a delay between oocytecollection and insemination allows the immature oocytes collected tocomplete its meiotic maturation in the culture media (10, 11). TheClamart's IVF working group in France, led by Jacques Testar,developed a luteinizing hormone-Surge Initiating Rise (LH-SIR) assaythat could detect the LH-surge at its initial rise (not at its peak) inhuman plasma for an accurate prediction of ovulation and best timing foroo-cytes retrieval (6, 12).

In 1982, the first IVF twins, Taylor and Freddie Axton, were bornat Queen Elizabeth hospital in King's Lynn, United Kingdom. Thefirst French IVF babies were born in the same year; Amandine, at Clamartin February followed by Alexia at Hopital Sevres in June (6). The firstSwedish IVF baby was born in Gothenburg (13). The first frozen embryotwins were born in Australia in 1982 and the world's first deliveryafter intrauterine insemination (IUI) was done in the same year as well(6). On April 16th at the University Hospital in Erlangen, Oliver, theGermany's first test-tube baby was born by caesarean section andZlatan Jovanovic was the first IVF baby born in Vienna's AKHhospital in Austria. Culture media for growing embryos started to beused (14). Richard Fleming was the first who demonstrated thatgonadotrophin releasing hormone (GnRH) agonists could be used toeliminate premature luteinization of the graffian follicles and controlthe process of ovarian stimulation (15). Danish gynaecologists, SusanLenz and Jorgen G Lauritsen, demonstrated how to use the ultrasound as aguide for trans abdominal trans-vesical oocyte aspiration (16).

In 1983, Alan Trounson's working group in Australia succeededto achieve the first pregnancy in a woman with bilateral oophorectomy byusing donor oocytes (17) and in an infertile woman with primary ovarianfailure by using donor embryo (18). The Monash IVF team in Australiareported a successful pregnancy by the first frozen embryo (19). In thesame year, in-vitro maturation (IVM) for fertilizing immature oocyteswas introduced (20). Gleicher and his colleagues reported the early useof vagin*l route oocytes retrieval via culdocentesis by the aid oftransabdominal ultrasonography (21). Robert Casper and his co-workerswere the first to describe the use of low dose human chorionicgonadotrophin (hCG) to support the luteal phase in assisted ovariancycles (22). The first report on the Canadian IVF baby, Robert JohnSaunders Reid, was written by the working group of Victor Gomel at theUniversity of British Columbia. In the same year, the birth ofworld's first IVF triplets was reported by Christopher Chen.

In 1984, the world's first IVF quadruplets were born onJanuary 6th at the Royal Women's Hospital, in Melbourne, Australia.On March 28th, the birth of the world's first frozen embryo, ZoeLeyland, was a breakthrough in ART history. This baby was delivered bycaesarean section at the Queen Victoria Medical Centre in Melbourne,Australia by Alan Trounson and Carl Wood (6). During the year 1984, thefirst legislation to regulate the IVF and human embryo research in theAustralia by Government of Victoria, the Infertility (MedicalProcedures) Act 1984, was promulgated (6, 23). The first surrogacyembryo transfer baby was born in California, USA, (6) while the firstreported pregnancy following trans laparoscopic gamete intrafallopiantransfer (GIFT) was announced by the endocrinologist Ricardo Asch (24).The first pregnancy following IVF and oo-cyte donation in a woman withprimary ovarian failure was successful (25). The early trans vagin*loocyte retrieval was introduced by Pierre Dellenbach and his colleaguesin Strasbourg, France (26). The first two pregnancies following thetransfer of intact frozen-thawed embryos were successful (27).

In 1985, the first pregnancy achieved by IVF using percutaneousepididymal sperm aspiration (PESA) succeeded (28). It was the year ofthe first human birth after replacement of hatching blastocystcryopreserved at an expanded blastocyst stage (29). A Nordic group, ledby the gynaecologist Matts Wikland in Gothenburg, Sweden, described thepossibility of using transvagin*l scanning for oocyte retrieval for thefirst time (30). By this technique, the ovaries' visualization wasmore effective than by the abdominal approach, and the smaller follicleswere easily punctured. The procedure could be done under localanaesthesia and the patient could leave the IVF center after an hour.The first report on the use of abdominal ultrasonography as a guide forembryo transfer was published. (31) Dan Szollosi with JacquelineMandelbaum described the microstructures of the human oocyte, whichbecame known as "Oocyte Dysmorphia" (32). Testart's groupin France published impressive results about using propanediol andsucrose as cryoprotectants for embryo freezing, instead of usingdimethyl sulphoxide (DMSO) (33). Quinn and Warnes published a formulaentitled Human Tubal Fluid (HTF) that mimics in vivo environment towhich the embryo is exposed (34). The European Society of HumanReproduction and Embryology (ESHRE) was established by the help ofRobert Edwards (from UK) and Jean Cohen (from Paris) after its firstmeeting in Bonn in 1985.

In 1986, Lupron[R] (GnRH agonist) was used for the first time toprevent premature ovulation. Monash IVF team reported the world'sfirst pregnancy achieved by surgical sperm retrieval from a patient withbilateral vas deferens ducts obstruction (6). Wilfried Feichtinger andPeter Kemeter used ultrasound-guided trans-vagin*l needle aspiration ofmature graffian follicles for oocytes retrieval (35). It was the year ofthe first successful pregnancy following IVF donated oocytes which wasachieved by a woman with non-ovarian failure, Zev Rosenwaks (36). DanielNavot and his co-workers reported the ability to induce endometrialcycles artificially and to establish pregnancy in the absence offunctioning ovaries (37). Paul Devroey and his colleagues reported thefirst successful pregnancy following laparoscopic zygote intrafallopiantransfer (ZIFT) (38). The introduction of the direct intraperitonealinsemination (DIPI) was in 1986 (6). Christopher Chen in Australiareported the world's first pregnancy resulting in the birth oftwins by using a previously cryopreserved oocyte (slow freezing withdimethylsulfoxide-DMSO/rapid thawing technique) (39). The first SovietIVF baby, Lena, conceived at Leonov's laboratory in Moscow was bornin February. A few months later, another IVF child, Kirill, Lena'sbrother, was born in Saint Petersburg.

Melissa Stern (Baby M) was born on March 27th in the United States.Her surrogate and biological mother, Mary Beth Whitehead (who conceivedby artificial insemination) refused to yield custody of Melissa to thecouple (William Stern and his wife, Elizabeth Stern) with whom she madethe surrogacy contract. The court of New Jersey found it in the bestinterest of the infant to award custody of Melissa to her biologicalfather William Stern and his wife Elizabeth Stern, rather than to hersurrogate mother, Mary Beth Whitehead.

In 1987 (Figure 2), the first report on using ultrasound machineduring embryo transfer (ET) was published. Laws-King and his co-workersreported a new technique called SUZI (sub-zonal injection) that wouldadvance assisted reproductive technology and offers a hope for coupleswith recurrent failed cycles (40). The introduction of a new effectivemethod, Ultra-rapid freezing, for cryopreservation of the human embryoswas in 1987 (41). Norway was the first country in the world to pass alaw on ART on June 12th, 1987 (Norwegian law on Assisted Reproductionand Genetics). In the Nordic law, treatment is limited to the married orcohabiting couples. Same sex couples, lesbians and single women wereexcluded from the IVF treatment and further surrogacy and embryodonation was not permitted.

In 1988, Patrick Christopher Steptoe died on March 21st. In thesame year, the world's first baby after home monitoring offertility treatment was born (6). Leeanda Wilton and Alan Trounsonintroduced the early embryo biopsy technique for genetic study (42). Thefirst report about two babies born after microsurgical epididymal spermaspiration (MESA) in men with congenital bilateral absence of vasdeferens (CBAVD) was published in 1988 (43). In May, Linda Kirkman gavebirth to Alice, who was conceived from her mother Maggie's egg,fertilized by sperm from a donor since her husband, Sev, had no sperm.The world's first IVF surrogate birth occurred in Australia (6). Itwas the year of the successful pregnancy achieved through sub-zonalsperm injection (SUZI), (44) and after oocyte zona pellucida drillingand mechanical partial zona dissection that facilitated spermpenetration (45).

In 1989, the first report on biopsy taking from pre-implanted humanembryos and sex detection by DNA amplification was published (46). Itwas the same year when laser was used for the first time in the field ofassisted reproduction (47). Yael Gonen and her co-workers in Toronto,Canada, pioneered the use of ultrasound for assessment of endometrialquality instead of IVF procedures (48).

[FIGURE 2 OMITTED]

In 1990, successful deliveries following human embryovitrification, (49) and biopsy of preimplantation embryos sexed byY-specific DNA amplification were reported (50). A Dutch embryologist,Jacques Cohen, published the first report on assisted hatching in humanembryos (51). The use of first polar body biopsy for genetic diagnosiswas done in the same year (52). Yael Gonen and her co-workers proposedthe use of GnRH agonist instead of hCG to trigger the endogenousLH-surge for IVF cycles (53). The use of combined oral contraceptivepills for follicular synchronization and cycle scheduling in IVF programhas been suggested (54). The British Human Fertilization and EmbryologyAct set out a framework for ART practice and research under the licensefrom the Human Fertilization and Embryology Authority (HFEA) (6).

In 1991, in vitro maturation (IVM) of donor oocytes in anon-stimulated cycle resulted in a successful pregnancy (55). GnRHantagonist was introduced to prevent premature LH-surge in a controlledovarian hyperstimulation program (6). Daniel Palanker used Excimer laserfor zona pellucida drilling (56).

In 1992, the first successful pregnancy after intracytoplasmicsperm injection (ICSI) by Gianpiero Palermo and Andre Van-Steirteghem occurred in Brussels, Belgium (57). A further successful in-vitrofertilization and embryo transfer (IVF-ET) was achieved after treatmentwith recombinant human FSH (rh-FSH) (58). It was the year of delivery ofthe first British SUZI treated baby. Two births were recorded byPasquale Patrizio from frozen embryos produced by epididymal aspiratedsperm (59). A published scientific report stated that men withcongenital bilateral absence of vas deferens (CBAVD) have a mild form ofcystic fibrosis (CF) (60). Administration of luteinizing hormonereleasing hormone (LHRH) agonist induced ovulation by triggeringendogenous LH-surge (61).

In 1993, Sherman Silber and his co-workers reported, for the firsttime, that infertile men with non-obstructive azoospermia become able tofather their own babies by the use of Testicular Sperm Extraction (TESE)and ICSI procedures (62). The genetic cause of congenital bilateralabsence of vas deferens (CBAVD) among infertile men (cystic fibrosismutations) could be transmitted to their offspring (63). The first livebirth was reported following treatment with rh-FSH (64).

In 1994, a successful in-vitro oocyte maturation (IVM) andfertilization in non-ovulating women with polycystic ovary (PCO)syndrome was achieved by Alan Trounson and his co-workers in Australia(65). It was the year of birth of the first British triplets aftermaternal surrogacy (6). The first IVF unit in the world, MidlandFertility Ser vice in United Kingdom was accredited with ISO 9002:1994.The first highly purified FSH preparation was developed (66) and thefirst pregnancy after the use of r-hLH was recorded (67).

In 1995, a successful human birth was reported by Frank Barnesafter in vitro primary oocyte maturation (IVM), ICSI, and assistedhatching (68). The first report of aneuploidy testing was published byJacques Cohen, (69) while the first report of spermatids to achievepregnancy was published by Simon Fishel and Green (70). Dmitri Dozortsevand his co-workers discovered oocyte activation during ICSI proceduretriggered by a water-soluble, heat-sensitive, non-species, specificcytosolic sperm factor (71).

In 1996 (Figure 3), Manuel Gil-Salom and his co-workers reportedsuccessful pregnancies employing ICSI after cryopreserved testicularsperm (72). The males with severe oligo-asthenozoospermia werediscovered to have deletion in their Y-chromosomes (6). AndreaJurisicova, a Canadian embryologist, was the first who recognized thatpreimplantation embryo fragmentation leads to a programmed cell death(73). Robert Casper and his colleagues at the University of Toronto,Canada used hypo-osmotic swelling test for selection of viable immotilesperm for ICSI procedure in men with complete astheno-zoospermia (74).Although the successful fertilization of a human oocyte by a late stagespermatid using ICSI was first reported by Vanderzwalmen in 1995, it wasnot before the year 1996 when Jan Tesarik and Simon Fishel announced thedelivery of the world's first two successful testicular spermatidbabies (6). This technique introduced the concept of using immaturesperm (spermatids) to overcome the problem of males'non-obstructive azoospermia (75). On July 5th, Ian Wilmut and KeithCampbell, succeeded to clone a sheep (Dolly) at Roslin Institute inScotland by using cells from the mammary glands of an adult sheep andenucleated egg cell.

[FIGURE 3 OMITTED]

In 1997, Sun, Jurisicova and Robert Casper described the use ofterminal deoxynucleotidyl transferase-mediated dUTP-biotin end labeling(TUNEL) for detection of DNA fragmentation in sperm and its correlationto IVF outcome (76). They found that sperm with fragmented DNA were lesslikely to fertilize the oocytes. The first successful birth after thetransfer of enucleated donor oocyte cytoplasm into a recipient oocyte(Ooplasm Donation) was in 1997 (77). The Australia's first twinswere born after open testicular biopsy. Gamete intra-fallopian transfer(GIFT) was accomplished by Porcu and Dal Prato through trans-cervicalfalloposcopy (78).

In 1998, Hannatu Kupchi, the first successful IVF baby, was born inNigeria. The first case report on a successful pregnancy aftercontrolled ovarian hyperstimulation induced by recombinant FSH and GnRHantagonist (Ganirelix[R]) was published by Joseph Itskovitz-Eldor (79).David Gardner at Colorado Center for Reproductive Medicine in the USAintroduced a serum-free medium for blastocyst transfer and culture (80).Gianpiero Palermo and his assistants succeeded to get sperm from menwith non-mosaic Klinefelter's syndrome by testicular extraction andachieve pregnancy by using ICSI procedure (81). A live birth followingcryopreservation of immature oocytes, thawing, IVM and thenfertilization through ICSI procedure took place (6). The DNA sequence ofthe human chromosomes (Human Genome Project) was broadcasted. OnDecember 1998, the first set of octuplets in the world (8 babies; 6girls and 2 boys) were born at St. Luke's Episcopal Hospital inHouston, Texas, USA, after the use of ovulation induction therapy to aNigerian-born American couple, Nkem Chukwu and Iyke Louis Udobi. MonashIVF-team in Australia announced the birth of twins by using CellRobotics Laser Assisted Hatching technique (6).

In 1999, the first unaffected pregnancy was reported after usingpreimplantation genetic diagnosis (PGD) for sickle cell anemia (82).Lilia Kuleshova and her colleagues announced a successful birthfollowing vitrification of a human oocyte (83). During this year, theworld's first baby was born to a man after multiple ejacul*teresuspension centrifugation technique. Ri-Cheng Chian and his colleaguesdemonstrated that hCG priming prior to immature oocyte retrieval inwomen with PCO syndrome increases oocyte maturation and pregnancy rate(84). The world's first baby for a patient with cystic fibrosis wasborn. It was the world's first successful IVF-ICSI pregnanciesafter airplane transport of oocytes as reported by McGill ReproductiveCentre, Toronto, Canada (85). Denmark reported the highest number of IVFcycles (1826 cycles) per million inhabitants followed by Finland (1440cycles) and then Sweden, Iceland and Norway (around 1000 cycles). Theseexceptionally high numbers of IVF cycles are probably due to acombination of relatively high practice levels in the Nordic countriesand a high public recognition of the technique (86). In spite of that,Louise Brown's younger sister, Natalie, in the United Kingdom whowas also conceived through IVF in 1982 (the world's 40th IVF baby)was the first IVF baby in the world to give birth herself, naturally, toa daughter named Casey on May 1999.

In 2000, Kutluk Oktay and Guvenc Karlikaya were the first to reporton the success of human ovarian tissue transplant after frozen storage(87). The first successful pregnancy in Japan was achieved throughblastocyst vitrification. A completely defined new protein-free embryoculture medium was introduced (6).

In 2001, the implantation rate on the running IVF programs wasimproved by using trans-vagin*l ultrasound guided embryo transfercatheter (88). Ri-Cheng Chian and his co-workers reported a successfulbirth of an infant developed from cryopreserved embryo which wasproduced by IVM oocytes and was delivered by a non-stimulated woman withPCO syndrome (89). Mc Gill group in Canada reported the first ongoingtwin pregnancy after ICSI of PESA retrieved spermatozoa into in vitromatured oocytes (90). A baby was born after sperm retrieval from amoribund man (91). The first British license was awarded for PGD andHLA-tissue typing (6). Australian scientists succeeded in fertilizingmice eggs without using sperm. This step opened the door for futuresingle-sex procreation. The first human cloned 6-cell embryos wereachieved by a private American company, Advanced Cell Technology for thepurpose of stem cell research (6).

In 2002, Kylie de Boer and her assistants reported the first livebirth after blastocyst biopsy for PGD (92). A comparative genomichybridization and polar body testing for PGD of chromosomal aneuploidywere applied for the first time (93).

In 2003, Tae-Ki Yoon and his working group reported a live birthafter vitrification in a stimulated IVF-ET program (94). The first IVFbirth after ovarian stimulation by a long-acting human recombinantfollicle stimulating hormone (rFSH) agonist was reported (95). Dr.Barash and Prof. Dekel demonstrated increased IVF implantation ratefollowing endometrial curettage by Pipelle curette as a simpleoutpatient procedure (96).

In 2004, Jacques Donnez reported the first live birth baby afterorthotopic transplantation of cryo-preserved ovarian tissue (97).Fertility preservation programs for women undergoing cancer treatmentusing IVM and oocyte vitrification were provided (98). The first reporton the natural ovulatory cycle in IVF combined with IVM as a potentialapproach to infertility treatment was published (99). David Gardner andhis colleagues performed the world's first single blastocysttransfer trial to improve pregnancy rate and to reduce the risk ofmultiple gestation (100). The British National Health System (NHS)funded PGD program and preimplantation HLA-tissue typing (101). A Koreangroup claimed to produce the first cloned human blastocyst. Furthermore,a live baby birth following pre-implantation genetic diagnosis forRetinoblastoma took place (102).

In 2005 (Figure 4), Adriana Iliescu was reported as theworld's oldest mother to give birth at the age of 66 years and 320days at Giulesti Maternity Hospital, Bucharest, Romania. She had an IVFusing donated eggs and sperm. Sherman Silber, in USA, announced thefirst case of successful ovary transplantation between two identicaltwin sisters discordant for ovarian function. The first birth fromthawed ovarian cortex transplants in a woman with post-chemotherapyovarian failure was reported (103). The first baby was born alive aftertrophectoderm biopsy and preimplantation genetic testing of humanblastocysts for beta Thalassaemia (104).

In 2006, Mohamed Bedaiwy and his group reported a successfulcryopreservation of intact human ovary with its vascular pedicle (105).The first successful pregnancy after PGD for aneuploidy screening inembryos was generated from a natural ovulatory cycle reported by McGillReproductive Centre, Toronto, Canada (106). Maria del Carmen Bousadabecame the world's oldest mother to give birth to twins at the ageof 66 years and 358 days in Spain. She conceived by the aid of IVF usingdonated eggs and sperm. On December 20th, Louise Brown (the world'sfirst IVF baby) who married to a nightclub security officer WesleyMullinder gave birth herself to a naturally conceived son Cameron, at StMichael's Hospital in Bristol, United Kingdom.

In 2007, the first baby was born alive from an egg that had beenmatured in vitro, frozen, thawed and then fertilized at McGillReproductive Center, Canada (6). A report was published from the Mc GillReproductive Center in Canada and the Maria Infertility Hospital inKorea on successful births after transfer of blastocysts that derivedfrom matured oocytes by IVM (107). The first European baby was bornafter screening by using comparative genomic hybridisation (CGH) (6).The concept of mild treatment strategy that substantially reduces therisk of multiple gestation and overall costs was widely held (108).Pasquale Patrizio introduced a novel multi-gradient freezing techniquefor cryopreservation of the whole ovary that resulted in preservation ofthe normal ovarian architecture (109).

[FIGURE 4 OMITTED]

In 2008, a viable pregnancy was achieved for the first time in a 38year old woman who carried a defective BRCA2 gene. Son Weon-Young andhis colleagues recommended 38 hr interval between hCG injection andoocyte retrieval to increase in vivo and in vitro oocyte maturationrates (110). On December 2008, the Midland Fertility Services in the UKlaunched vitrification flash-freezing process. The first report, atMonash immunology and stem cell laboratories (MISCL), on DNAfingerprinting to identify the blastocyst of the origin for live birthsand that of gene expression profiles of biopsied trophectoderm coulddiscriminate between viable and non-viable blastocysts (111). The firsthealthy twins were delivered after oocyte cryopreservation and bilateralovariectomy for ovarian cancer (112). Rajo Devi Lohan and Omkari Panwarbecame the world's oldest mothers to give birth at the age of 70years in India.

In 2009, octuplets (8 babies; 6 boys and 2 girls) were born toNadya Suleman, a 33 year old Iraqi-American woman in California, USA(The second octuplets in the world). Her treating doctor Michael Kamravahad transferred twelve frozen embryos that left from her previousstimulated IVF cycles, which the medical board of California found it tobe a "life-threatening practice" and withdrew his medicallicense. The first baby boy was born from vitrified oocytes in Australia(6). Cetrorelix acetate (LHRH antagonist) was approved by FDA forclinical use in IVF programs. Simon Fishel and his working group fromCARE Fertility, Nottingham, reported a live birth after polar body arraycomparative genomic hybridization (113).

In 2010, the Midland Fertility Services in the UK confirmed thefirst successful pregnancy from vitrified blastocysts. Several minorchanges to the 8th HFEA Code of Practice were incorporated into theprint version of the Code on April 2010. The Nobel Assembly atKarolinska Institute, Sweden, offered the 2010 Nobel Prize in Physiologyor Medicine to the British physiologist, Robert Edwards for hisremarkable work in the field of in vitro fertilization. An Indian womanbecame the oldest mother in the world to have triplets at the age of 66years. After being childless for 44 years of marriage, Bhateri Devi gavebirth to two boys and a girl after IVF.

In 2011, the novel monitoring system for continuous observation ofearly embryo development around the hour (EmbryoScope[R]) was introducedby Unisense Fertilitech, USA. In December, Clare and Charlotte were theworld's first twins born to Ed and Caroline Marks by use of the newEmbryo Scpe[R] at Cleveland Reproductive Center, Ohio, USA.

In 2012, the family of Lesley Brown, the first world's IVFmother, confirmed her death at Bristol Royal Infirmary. In the sameyear, the world's five-millionth IVF baby was born.

In 2013, Professor Sir Robert Edwards, scientist and co-pioneer ofIVF, passed away peacefully in his sleep on the morning of April 10thafter a long illness. In April, the first baby was born, Heath atHammersmith hospital, UK to Suzannah and Calum Kidd, from Hitchen, byusing a new lower risk IVF treatment, Kisspeptin for induction ofovulation without the risk of ovarian hyper stimulation syndrome (aclinical trial NCT01667406 led by Professor Waljit Dhillo at ImperialCollege London). In May, a group of scientists led by ShoukhratMitalipov, a reproductive biology specialist at Oregon Health SciencesUniversities (OHSU) published a report on a successful human cloning.The approach involved nuclear transfer from human fibroblasts toenucleated oocytes and resulted in viable embryos developing to theblastocyst stage. The researchers planned to obtain embryonic stem cellfrom these developed blastocysts for the purpose of therapeutic cloning.Alison Campbell, a senior British clinical embryologist in Manchester,introduced the novel Time-lapse imaging for early developingpreimplantation embryos for clinical selection of healthy-lookingembryos without the need for biopsy and preimplantation geneticscreening (PGS) in cases with recurrent IVF failure (114).

Bottom of Form: In June, Ruth Carter, 42-year-old clinicalpsychologist, became the world's first mother to give birth to agirl at Liverpool's Women Hospital, UK after using the new systemEarly Embryo Viability Assessment (Eeva) implementing the Time-lapseimaging technique.

ART Expectations: The prospects hold promise for rapid evolution inART. Advances in molecular medicine will help in mapping the Ychromosome. Males with testicular failure will be able soon to fathertheir own genetic children. Future researches with oocyte maturation,culture media and endometrial receptiveness may allow immature oocyteretrieval with in vitro maturation to replace the conventional in vitrofertilization. Cryopreservation of human oocytes will provide analternative to embryo cryopreservation with its ethical repercussions.Advances in Time-lapse imaging technique will increase IVF success rateand avoid the need for invasive and expensive preimplantation geneticdiagnosis (PGD) to screen out abnormal embryos. New drugs such as GnRHantagonists hold promise of leading to a better ovarian stimulation, eggquality and implantation rates. The transfer of cytoplasm from youngerdonor oocytes into older oocytes may improve the viability of developingzygotes and give a better chance for older women to carry their ownbiological babies.

Conclusion

Advances in assisted reproductive technology for infertile coupleswere among the great medical successes of the last century. ART has madehuge strides and fast progress towards finding suitable treatmentoptions for each infertile couple. Costs and complexity of treatmenthave been reduced to alleviate the stress and social troubles. Problemsrelated to the risk of multiple pregnancy and the use of stimulatedcycles are nearly solved and new techniques for management of severemale factor infertility and the detection of genetic anomalies in theembryo prior to transfer are being introduced. Further refinements ofthe techniques and modification of treatments will probably occur withongoing use and practice.

Acknowledgement

The author deeply acknowledges the assistance of medical fellows atSt Michael hospital and staff of the Faculty of Medicine and Dentistry,University of Bristol. The help of The Bristol Centre for ReproductiveMedicine, Southmead Hospital is highly appreciated.

Conflict of Interest

I hereby declare that this work is carried out in accordance withthe requirements of the University of Bristol Regulations and Code ofEthics for Research Programs. Furthermore, it is approved by theResearch Review Board. Except where indicated by specific reference inthe text, this work is my own and there was no contribution of any otherauthors. Any views expressed in the study are those of the author. Thework was self-funded. I did not receive any financial funding or supportfrom any person or institution. In addition, I state that I have nocompeting interests.

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Remah Moustafa Kamel *

Department of Obstetrics and Gynaecology, Faculty of Medicine,Dammam University, Dammam, Saudi Arabia

* Corresponding Author: Remah Moustafa Kamel, 4 Tyndall's ParkRoad, Clifton, Bristol, BS8 IPG, United Kingdom

E-mail: [emailprotected]

Received: Apr. 10, 2013

Accepted: Aug. 4, 2013