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Editorials

What is new in IVF?

Assisted has come a long way in 40 years

Gabor T Kovacs t was just over 40 years ago that the fi rst ever human now becoming the preferred method in leading IVF units MD, FRANZCOG, CREI Director conceived through in-vitro around the world. This not only more closely matches (IVF) was reported by the team from Melbourne.1 the normal physiological process of conception, in which Monash IVF, Melbourne, VIC. I Unfortunately, the pregnancy only lasted for a few days the reaches the uterine cavity at the gkovacs@ and was what we would now call a biochemical preg- stage (Day 5 after fertilisation) rather than the cleavage monashivf.com nancy. It took another 5 years before , the stage (Day 2 or 3), but it also allows a more scientifi c world’s fi rst IVF child, was born in the United Kingdom selection of the “best” embryo. Another major advance doi: 10.5694/mja14.01000 on 25 July 1978, through the efforts of and in the laboratory is the use of time-lapse photography of 2 Bob Edwards, from their 102nd human . embryo development, which is being used to predict the The British team had another birth, a less well known embryo most likely to result in a successful pregnancy. Alastair MacDonald, in January 1979, but the next 11 The other change is the use of vitrifi cation rather than 33,4,4 births occurred in Melbourne. slow freezing to preserve , a technique that is Melbourne then became the international centre for better suited to blastocyst freezing, with survival rates IVF, not only converting the process to clinical treat- exceeding 95%.1144 ment with a near 10% success rate by using stimulated There has been a move towards single embryo trans- cycles,5 but also pioneering world-fi rsts such as embryo 6 7 8 fer (SET), in which Australia is again leading the world. freezing, , in-vitro maturation, blastocyst While may be “cute” and seem like a good solution transfer9 and microinjection techniques — although the for childless couples, the perinatal morbidity and pos- fi rst human birth using microinjection was in Singapore. sible long-term medical and social problems of a multiple IVF was initially developed to overcome tubal disease pregnancy1155 mean that moving towards SET is the only before being adapted for use in women with unexplained responsible way to go. We have recently reported that the subfertility.1100 It also became the fi rst effective treatment chance of taking home a healthy, full-term baby is higher of male subfertility.1111 if SET rather than double embryo transfer is performed.1166 Now, in 2014, IVF is practised in virtually every de- IVF has also been used in the area of pre-implantation veloped country. Well over fi ve million babies have been genetic diagnosis for fertile couples who do not want to born using the technology, from fresh and frozen embryo resort to antenatal diagnosis and possible termination of transfers. There have been several changes to the practice of IVF pregnancy when they are at risk of transmitting serious in recent years. genetic conditions. For controlled ovarian hyperstimulation (COH), the More recently, IVF technology has been applied to ability to predict response by measuring the anti-Mülleri- preservation. This can be undertaken by freezing an hormone level1122 has introduced greater precision. The embryos, oocytes or ovarian tissue, with subsequent IVF application of -releasing hormone (GnRH) treatment. The fi rst successful Australian pregnancy after antagonist regimens has enabled shorter treatment cycles, frozen ovarian tissue autotransplantation, which resulted and the availability of a long-acting follicle-stimulating in the birth of a healthy female baby, was reported in the 1177 hormone injection (corifollitropin alfa) has reduced the Journal in 2013. This was followed by a set of IVF twins number of injections women have to administer. The born after implanting ovarian tissue into the anterior 1188 risk of ovarian hyperstimulation syndrome, a potentially abdominal wall. serious complication of COH, has been almost eliminated Another exciting development is the possibility of ther- by the ability to induce ovarian maturation by using a apeutically improving the mitochondria within oocytes GnRH agonist in GnRH antagonist cycles. in the IVF laboratory. In the UK, the Human Fertilisation The technique of oocyte collection has changed little and Authority is in the process of approv- since the introduction of the transvaginal ultrasound- ing the use of mitochondrial transfer from a third-party guided technique in 1985,1133 although there has been move- donor in the case of . A modifi ca- ment from the operating theatre to procedure rooms in tion of this technique is the use of autologous germline some centres. mitochondrial energy transfer (AUGMENT; OvaScience), There have also been major changes in the IVF labora- which acts a bit like putting a new battery in an old car, tory. Although fi rst reported in 1998,9 blastocyst transfer is and may make older eggs more fertile.

244 MJA 201 (5) · 1 September 2014 Editorials

We have come a long way in 9 Jones GM, Trounson AO, Gardner DK, et al, Evolution of a culture protocol for successful blastocyst development and pregnancy. Hum Reprod 1998; during the past 40 years, and I cannot even imagine where 13: 169-177. the next 40 years will take us. 10 Trounson AO, Leeton JF, Wood C, et al. The investigation of idiopathic Competing interests: I am a shareholder in Monash IVF. by fertilization. Fertil Steril 1980; 34: 431-438. 11 Yates CA, Thomas C, Kovacs GT, de Kretser DM. Andrology, male factor Provenance: Commissioned; externally peer reviewed. infertility and IVF. In: Wood C, Trounson A, editors. Clinical in vitro fertilization. 2nd ed. London: Springer-Verlag, 1989: 95-111. 1 de Kretzer D, Dennis P, Hudson B, et al. Transfer of a human . Lancet 1973; ii: 728-729. 12 Nelson SM, Yates RW, Lyall H, et al. Anti-Müllerian hormone-based approach to controlled ovarian stimulation for assisted conception. Hum 2 Steptoe PC, Edwards RG. Birth after the reimplantation of a human embryo. Reprod 2009; 24: 867-875. Lancet 1978; ii: 366. 13 Kovacs GT, King C, Cameron I, et al. A comparison of vaginal ultrasonic- 3 Lopata A, Johnston IW, Hoult IJ, Speirs AI. Pregnancy following intrauterine guided and laparoscopic retrieval of occytes for in vitro fertilization. Asia implantation of an embryo obtained by in vitro fertilization of a Oceania J Obstet Gynaecol 1990; 16: 39-43. preovulatory egg. Fertil Steril 1980; 33: 117-120. 14 Potdar N, Gelbaya TA, Nardo LG. Oocyte vitrifi cation in the 21st century and 4 Wood C, Trounson A, Leeton J, et al. A clinical assessment of nine post-warming fertility outcomes: a and meta-analysis. obtained by in vitro fertilization and embryo tranfer. Fertil Steril Reprod Biomed Online 2014; 29: 159-176. 1981; 35: 502-508. 15 Kovacs GT, Breheny S, Maclachlan V, et al. Outcome of pregnancies 5 Trounson AO, Leeton JF, Wood C, et al. Pregnancies in humans by achieved by techniques and diagnosed as twins at the 6 fertilization in vitro and embryo transfer in the controlled ovulatory cycle. week ultrasound. Aust N Z J Obstet Gynaecol 2004; 44: 510-513. Science 1981; 212: 681-682. 16 Wang YA, Kovacs G, Sullivan EA. Transfer of a selected single blastocyst 6 Trounson A, Mohr L. Human pregnancy following , thawing optimizes the chance of a healthy term baby: a retrospective population and transfer of an eight-cell embryo. 1983; 305: 707-709. based study in Australia 2004–2007. Hum Reprod 2010; 25: 1996-2005. 7 Trounson A, Leeton J, Besanko M, et al. Pregnancy established in an infertile 17 Burmeister L, Kovacs GT, Osianlis T. First Australian pregnancy after ovarian patient after transfer of a donated embryo fertilised in vitro. Br Med J (Clin tissue cryopreservation and subsequent autotransplantation. Med J Aust Res Ed) 1983; 286: 835-838. 2013; 198: 158-1 59. 8 Trounson A, Anderiesz C, Jones G. Maturation of human oocytes in vitro and 18 Stern CJ, Gook D, Hale LG, et al. Delivery of twins following heterotopic their developmental competence. Reproduction 2001; 121: 51-75. grafting of frozen-thawed ovarian tissue. Hum Reprod 2014; 29: 1828. 

Changes to cervical screening in Australia: applying lessons learnt The potentially more eff ective new program will rely heavily on successful implementation

n Australia, the organised approach to preventing cer- shows a signifi cant reduction in screening participation Annabelle Farnsworth MB BS(Hons), FRCPA, FIAC vical cancer began over 20 years ago. This approach in 20–24-year-old and 25–29-year-old vaccinated women Medical Director,1 and Ihas been a great public health success story that has compared with unvaccinated women in Victoria (37.6% Adjunct Professor2 resulted in substantial reductions in incidence of and v 47.7% and 45.2% v 58.7%, respectively, over the period 1 Douglass Hanly Moir 1 mortality from . The key reason for this 2010–2011).5 When HPV vaccination was being assessed, Pathology, success was recognition of the complexity of the screening modelling showed that vaccination alone would be less Sydney, NSW. 2 2 School of Medicine, pathway — which includes recruitment, sample taking, effective in reducing the incidence of cervical cancer than University of laboratory quality assurance, reporting, management 6 Notre Dame Australia, the current screening program. Consequently, when the Sydney, NSW. recommendations, follow-up and monitoring — and the vaccination program began, there was a public education afarnsworth@ need for high quality in each of these processes. Defi ned campaign emphasising that screening needed to continue. dhm.com.au quality standards were implemented, assisted by the The results of the study by Budd et al indicate that this establishment of Pap test registers. Over the same period, message has not been heeded. doi: 10.5694/mja14.00935 there has been a great increase in the understanding of In April this year, the Medical Services Advisory the pathobiology of cervical cancer, including its strong Committee announced recommendations to signifi cantly association with human papillomavirus (HPV) infection, alter cervical screening in Australia.7 The recommenda- which led to development of an HPV vaccine that provides tions include: replacing cytological testing for primary protection against the two HPV subtypes that are most screening with HPV testing using a molecular diagnostic strongly linked to cervical cancer. assay; increasing the age of commencement to 25 years; Australia successfully introduced an HPV vaccina- screening every 5 years until age 69–74 years; and using tion program in 2007. High coverage rates have been cytological testing for triage purposes in those who test reported3 and early data show a reduction in the incidence positive for HPV. These recommendations are based on of the vaccine-targeted viral subtypes.4 However, in this an extensive review of scientifi c literature and modelling issue of the Journal, research by Budd and colleagues studies of disease and cost-effectiveness. The review Research p 279

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