Preimplantation Genetics

Lead: Dr Joyce Harper

Main aims

UCL Centre for PGD has both clinical and research aims. We also run the MSc and post graduate diploma in Prenatal Genetics and Fetal Medicine which was set up in 1997.

Clinical

We have been performing preimplantation genetic diagnosis (PGD) since 1991. Three years ago we also introduced a programme of preimplantation genetic screening (PGS). The majority of our clinical research has been to develop single cell diagnosis for PGD and to develop an accurate method of analysing chromosomes for PGS. We are currently working towards laboratory accreditation.

Research

Our research concentrates on the origin of genetically determined human disease and the genetics of preimplantation embryo development.

Background

Since the successful application of in vitro fertilization in 1978, it has been possible to study the chromosomes of human preimplantation embryos. Preimplantation genetic diagnosis (PGD) was developed as an alternative to prenatal diagnosis, for couples at risk of transmitting an inherited disease to their offspring. With PGD, the couple undergo routine IVF procedures so that the embryos are produced outside the body. Embryo biopsy is usually undertaken when the embryo is at the 6-8 cell stage, and 1-2 blastomeres are removed. Single cell diagnosis is performed using the polymerase chain reaction (PCR) or fluorescent in situ hybridisation (FISH), depending on the disease being diagnosed. Unaffected embryos are then transferred to the uterus so that the pregnancy is started knowing that the fetus is unaffected. PGS uses PGD technology to determine the chromosome status of embryos produced by couples going through IVF or those with recurrent miscarriages.

Research stemming from our work on PGD has shown that the majority of embryos in vitro are chromosomally abnormal. A variety of studies have been conducted to investigate the origin of these abnormalities. Follow up studies on embryos found to be chromosomally abnormal after PGS allows us to investigate the reasons for reproductive failure. Follow up studies of embryos diagnosed with a single gene defect allow us to investigate a number of genetic disorders, such as DM.

Current Projects

Development of new PGD protocols, especially for the inherited cancers such as TP53, APC, RB1 and BRCA 1 & 2
Gene expression in preimplantation embryos
Investigation of mismatch repair in preimplantation embryos
Use of metaphase-CGH to study chromosomes in preimplantation embryos
Use of array-CGH for prenatal and preimplantation diagnosis
Whole genome amplification techniques
Analysis of the trinucleotide repeat sequence associated with the DM1 locus and its biological effect
Analysis of the methylation pattern in IVF embryos to study imprinting
Chromosome abnormalities of patients at high risk
The origin of binucleate cells

Main Achievements

UCL Centre for PGD was one of the first centres in the world to offer PGD. Our clinical achievements include the first use of FISH for sex determination, one of the first clinics to use FISH for the diagnosis of chromosome abnormalities, first UK centre to offer PGD for myotonic dystrophy (second centre worldwide) and first centre to specialise in PGD for inherited cancers. Some of our team were involved in setting up the ESHRE PGD Consortium (Joyce Harper is currently Chair and Sioban SenGupta is on the steering committee). Our group were responsible for the only text book on PGD published in 2001, and Joyce Harper is editing another PGD book with CUP. We are often invited to international conferences to talk about PGD. We have run 12 hands on PGD workshops.

For our research activities we were one of the first group to describe the level of chromosome abnormalities in human preimplantation embryos and the first to describe chaotic embryos. The majority of PGD clinics concentrate on clinical work but we are lucky to be able to study early human development in detail.

Key staff

Joy Delhanty, Emeritus Professor
Sioban Sengupta, Head Of Pcr
Karen Fordham, Nurse Co-Ordinator
Seema Dhanjal, Research Fellow
Barbara Smith, Research Fellow
Georgia Kakourou, Mlso/Phd Student
Thalia Mamas, Mlso/Phd Student
Leoni Xanthopoulou, Mlso/Phd Student
Anna Mantzouratou, Mlso/Phd Student
Anastasia Mania, Mlso
Stavros Glentis, Phd Student
Souraya Jaroudi, Phd Student
Soha Tashkandi, Phd Student

Future Plans

Development of array-CGH technology for prenatal and PGD.
Development of PGD for more diseases, especially the inherited cancers.
In depth study of the genetics of early human development.

Funding

MRC JREI Equipment Grant. Title: Molecular genetic and cytogenetic analysis of human gametes and preimplantation embryos Amount: £20,000 Date: January 1999. Joint with Joy Delhanty
Tommy’s Campaign. Project grant. Title: Innovative approaches to the prevention of recurrent miscarriage by preimplantation diagnosis of chromosome imbalance. Amount: £71,214 Duration: 2 years Date: January 2000- December 2002. Joint with Joy Delhanty
UCL Special Trustees Grant Title: Analysis of chromosomes in preimplantation embryos. Amount: £16,000. Duration two years. Date April 2001 - 2003
Lifeforce Research, Analysis of chromosomes in preimplantation embryos. Amount; £24,000. Duration 2 years. Date 2002-2004.
Wellbeing Grant, Grant title: Detection of chromosome anomalies in the first polar body by CGH and validation in the oocyte and embryo, Amount: £94,494. Duration 2 years. Date June 2004-2006. Joint with Joy Delhanty and Mike Faed
Saudi Government, Chromosome analysis of embryos and investigation of genomic imprinting. Amount; 77,000. Duration 3 years. Date 2004-2007
Lifeforce Research, Development of microarrays for analysis of human preimplantation embryos. Amount; £30,000. Duration 3 years. Date 2005-2008.
Lifeforce Research, Investigation of chromosomes in mouse and human embryos. Amount; £15,000. Duration 3 years. Date 2005-2008.

Publications

Co-Edited Books

Littleton, J.M., Harper, J.C., Hudspith, M.J., Pagonis, C., Dolin, S., and Little, H. (1988) Adaptation in neuronal calcium channels may cause alcohol physical dependence. In Psychotropic Drug Tolerance and Dependence. Eds. M. Lader, Croom Helm, pp 60-72
Littleton, J.M., and Harper, J.C. (1989) Cellular tolerance and dependence. In 'The Nature of Dependence' Oxford University Press. Eds. M. Lader and G. Edwards. pp113-134
Harper, JC and Delhanty, JDA (1996) FISH in preimplantation diagnosis. In Methods in Molecular Biology, Molecular Diagnosis of Genetic Disease. Ed. John Walker Humana (New York)
Delhanty, JDA and Harper, JC (2000) Preimplantation Genetic Diagnosis In: Diagnosis of Genetic Defects in the Fetus, Rodeck, CH, Ed. Ballière’s Best Practice & Research in Clinical Obstetrics and Gynaecology. Ballière Tindall London, 691-708
Harper JC (2000) Preimplantation Genetic Diagnosis In. In Vitro Fertilisation Eds Dale and Elder, Publishers Cambridge University Press
Harper, JC and Delhanty, JDA (1997 and 2000) Preimplantation Genetic Diagnosis. In Fetal Medicine: Basic Science and Clinical Practice. Editors Rodeck and Whittle. Publishers, Churchill Livingstone.
Harper, JC and Bui, TH (2002) Preimplantation Genetic Diagnosis, For Baillière’s – Best Practice and Research in Obstetrics and Gynaecology, volume 16, (5) Edited by Mark Evans and The-Hung Bui, Tindall London
Harper, JC and Doshi, A (2003) Micromanipulation: Biopsy In Laboratory guide to the mammalian embryo, Editors Gardner, Lane and Watson, Published by Oxford University Press
Harper, JC and Delhanty, JDA (2004) Clinical aspects of Preimplantation Genetic Diagnosis, In Good clinical practice in assisted conception. Publisher Cambridge University Press, Editors, Serhal and Overton, pp209-225

Referred Articles

Harper, J.C., Pagonis, C., and Littleton, J.M. (1987) Altered characteristics of catecholamine release from rat cortical slices and adrenal chromaffin cells in culture after chronic exposure to ethanol and the effect of dihydropyridines on these systems. Alcohol and Alcoholism 22 725-730
Littleton, J.M., Harper, J.C., Brennan, C.H., and Guppy, L.J. (1988) Adaptation in membrane calcium channels as a basis for alcohol-related pathology. Australian Drug and Alcohol Dependence Review 7 35-38
Harper, J.C., Pagonis, C., and Littleton, J.M. (1988) An adaptive increase in neuronal calcium channels alters catecholamine release in alcohol dependence. Neurology and Neurobiology 42 453-456
Harper, J.C., Brennan, C., and Littleton, J.M. (1989) Genetic up-regulation of calcium channels in a cellular model of ethanol dependence. Neuropharmacology 28 1299-1302
Harper, J.C., and Littleton, J.M. (1990) Development of tolerance to ethanol in cultured adrenal chromaffin cells. Alcohol Clin. Exp. Res. 14 508-512
Harper, J.C., and Littleton, J.M. (1990) Characteristics of catecholamine release from adrenal chromaffin cells in medium containing ethanol. I. Spontaneous and K+-induced release. Alcohol and Alcoholism 26 25-32
Harper, J.C., and Littleton, J.M. (1990) Characteristics of catecholamine release from adrenal chromaffin cells in medium containing ethanol. II. Carbachol- and veratrine-induced release. Alcohol and Alcoholism 26 33-38
Al-Shawaf, T., Serhal, P., Fiamanya., W., Harper, J.C., and Craft, I.L. (1990) Transfallopian tube embryo transfer: Successful pregnancy outcome. J. of IVF and ET 7 337-340
Webley, G., Richardson, M., Given, A., and Harper, J.C. (1990) Pre-incubation of human granulosa cells with gonadotrophin prevents the cloprostenol inhibition of progesterone production. Human Reproduction 6 779-782
Al-Shawaf, T., Nolan, A., Nadkarni, P., Harper, J.C., Brown, J., Guirgis, R., Emerson, G., Bayly, M., and Craft, I.L. (1991) The reproductive outcome following a superhigh response to stimulation in a gamete intrafallopian transfer program. J. of IVF and ET 8 202-207
Al-Shawaf, T., Nolan, A., Harper, J.C., Serhal, P., and Craft, I.L. (1991) Pregnancy following gamete intrafallopian transfer (GIFT) with cryopreserved semen from infertile men following therapy for lymphomas or testicular tumour: Report on three cases. Human Reproduction 6 365-366
Al-Shawaf, T., Nolan, A., Guirgis, R., Harper, J., Santis, M., and Craft, I. (1992) The influence of ovarian response on gamete intra-fallopian transfer outcome in older women. Human Reproduction 7 1106-1110
Al-Shawaf, T., Dave, R., Harper, J.C., Lineham, D., Riley, P., and Craft, I. (1993) Transfers of embryos into the uterus: How much do technical factors affect pregnancy rates? J. of Assisted Reproduction and Genetics. 10 31-36
Delhanty, J., Griffin, D., Handyside, A.H., Harper, J.C., Atkinson, G., Pieters, M.H.E.C., and Winston, R.M.L. (1993) Detection of aneuploidy and chromosomal mosaicism in human embryos during preimplantation sex determination by fluorescent in situ hybridisation (FISH). Human Molecular Genetics 2 1183-1185
Harper, J.C., Coonen, E., Ramaekers, F.C.S., Delhanty, J.D.A., Handyside, A.H., Winston, R.M.L., and Hopman, A.H.N. (1994) Identification of the sex of human preimplantation embryos in two hours using an improved spreading method and fluorescent in situ hybridisation (FISH) using directly-labelled probes. Human Reproduction 9, 721-724
Harper, J.C., Robinson, F., Duffy, S., Griffin, D., Delhanty, J.D.A., Handyside, A.H., and Winston, R.M.L. (1994) Identification of fertilisation in embryos with accelerated cleavage by fluorescent in situ hybridisation. Human Reproduction 9 1733-1737
Griffin, D.K., Handyside, A.H., Harper, J.C., Wilton, L., Atkinson, G.H., Soussis, I., Wells, D., Kontogianni, E.H., Tarin, J., Geber, S., Ao, A., Winston, R.M.L., and Delhanty, J.D.A. (1994) Clinical experience with preimplantation diagnosis of sex by dual fluorescent in situ hybridisation. J. Assist. Reprod. Genet. 11, 132-143
Coonen, E., Harper, J.C., Ramaekers, F.C.S., Delhanty, J.D.A., Hopman, A.H.N., Geraedts, J.P.M., and Handyside, A.H. (1994) Presence of chromosomal mosaicism in abnormal preimplantation embryos detected by fluorescent in situ hybridisation. Hum. Genet. 54 609-615
Harper, J.C., Coonen, E., Handyside, A.H., Winston, R.M.L., Hopman, A.H.N., and Delhanty, J.D.A. (1995) Mosaicism of autosomes and sex chromosomes in morphologically normal, monospermic, preimplantation human embryos. Prenatal Diagnosis 15 41-50.
Harper, JC., Dawson, K., Delhanty, JDA and Winston, RML. (1995) The use of FISH for the analysis of IVF embryos: a diagnostic tool for the infertile couple. Hum Reprod. 10 3255-3258
Harper, JC and Delhanty, JDA.(1996) Detection of chromosomal abnormalities in human preimplantation embryos using FISH. J. Assit Reprod. Genet. 13(2), 137-139
Soussis, J., Harper, JC, Kontogianni, E, Paraschos, T., Packham, D., Handyside, AH and Winston, RML. (1996) Pregnancies resulting from embryos biopsied for preimplantation diagnosis of genetic disease. Biochemical and ultrasonic studies in the first trimester of pregnancy. J. Assist Reprod Genet. 13 254-257
Ao, A., Ray, P., Harper, JC, Lesko, J., Atkinson, G., Paraschos, T., Taylor, D., Hughes, M., Handyside, AH., and Winston, RML. (1996) Clinical experience with preimplantation diagnosis of deltaF508 deletion in cystic fibrosis. Prenatal Diagnosis, 16, 137-142
Soussis, J., Harper, JC, Handyside, AH and Winston, RML. (1996) Obstetric outcome of pregnancies resulting from preimplantation diagnosis of inherited disease. Br. J. Obs. Gynae 103, 784-788
Delhanty, JDA, Harper, JC, Ao, A, Handyside, AH, and Winston, RML (1997) Multicolour FISH detects frequent chromosomal mosaicism and chaotic division in normal preimplantation embryos from fertile patients. Human Genetics, 99, 755-760
Conn CM, Harper JC, Winston RML & Delhanty JDA. (1998) Infertile couples with Robertsonian translocations: Preimplantation genetic analysis of embryos reveals chaotic cleavage divisions. Human Genetics 102: 117-123
Conn CM, Cozzi J, Harper JC, Winston RML, Delhanty JDA, (1999) Preimplantation genetic diagnosis for couples at high risk of Down syndrome pregnancy due to parental translocation or mosaicism Journal of Medical Genetics 36: 45-50
Cozzi, J, Conn, CM, Harper, JC, Winston, RML, Rindl, M., Farndon, PA, and Delhanty, JDA (1999) A trisomic germ cell line and precocious chromatid segregation leads to recurrent trisomy 1 conception Human Genetics 1999; 104: 23-28.
Harper, JC and Wells, D (1999) Recent Advances and Future Developments in PGD. Prenatal Diagnosis, 19, 1193-1199
Ray, PF, Harper, JC, Ao, A, Taylor, DM, Winston, RML, Hughes, M and Handyside, AH (1999) Successful PGD for sex linked Lesch Nyhan Syndrome using specific diagnosis. Prenatal Diagnosis 19, 1237-1247
Moore GE, Ruangvutilert P, Chatzimeletiou K, Bell G, Chen C-K, Johnson P and Harper JC (2000) Examination of trisomy 13, 18, and 21 fetal tissues at different gestational ages using FISH. European Journal of Human Genetics 8, 223-228
Ruangvutilert P, Delhanty JDA, Rodeck, C and Harper, JC (2000) Relative efficiency of FISH on metaphase and interphase nuclei from non-mosaic trisomic or triploid fibroblast cultures. Prenatal Diagnosis. 20, 159-162
Ruangvutilert P, Delhanty JDA, Serhal, P, Rodeck, C and Harper, JC (2000) FISH analysis on day 5 post insemination of human arrested and blastocyst stage embryos. Prenatal Diagnosis, 20, 552-560
A Ioulianos, D Wells, JC Harper, JDA Delhanty (2000) A successful strategy for preimplantation diagnosis of medium-chain acyl-CoA dehydrogenase (MCAD) deficiency Prenat Diagn 20, 593-598.
Piyamongkol, W, Harper, JC, Sherlock, JK, Doshi, A, Serhal, PF, Delhanty, JDA, Wells, D (2001) A Successful Strategy for Preimplantation Genetic Diagnosis of Myotonic Dystrophy using Multiplex Fluorescent PCR. Prenatal Diagnosis 21, 223-232.
Piyamongkol, W., Harper, J.C., Delhanty, J.D.A. Wells, D. (2001) Preimplantation genetic diagnostic protocols for alpha- and beta-thalassaemia using multiplex fluorescent PCR. Prenatal Diagnosis 21, 753-759.
Piyamongkol, W., Harper, J.C., Delhanty, J.D.A., Wells, D. (2001) PGD protocols using multiplex fluorescent PCR: beta-thalassaemia SEA mutation. Reproductive BioMedicine Online 2, 212-213.
Piyamongkol, W., Harper, J.C., Delhanty, J.D.A., Wells, D. (2001) PGD protocols using multiplex fluorescent PCR: myotonic dystrophy. Reproductive BioMedicine Online 2, 213-214
Apessos A., Abou-Sleiman P.M., Harper J.C. and Delhanty J.D.A. (2001) Preimplantation genetic diagnosis of the fragile X syndrome by use of linked polymorphic markers. Prenatal Diagnosis, 21, 504-511.
Abou-Sleiman P.M., Apessos A., Harper J.C., Serhal P. and Delhanty J.D.A (2002) Pregnancy Following Preimplantation Genetic Diagnosis for Crouzon Syndrome. Molecular Human Reproduction, 8, 101-104
Harper JC, Wells, D, Piyamongkol, W, Abou Sleiman, P, Apessos, A, Ioulianis, A, Davis, M, Doshi, A, Serhal, P, Ranieri, M, Rodeck, C and Delhanty, JDA (2002) PGD for Single Gene Disorders: Experience with five single gene disorders; Prenatal Diagnosis 22, 1-9
Abou-Sleiman P.M., Apessos A., Harper J.C., Serhal P., Winston R. M. L. and Delhanty J.D.A. (2002) First application of preimplantation genetic diagnosis to Neurofibromatosis type 2 (NF2), Prenatal Diagnosis 22
Wirawit Piyamongkol, Mercedes Garcia Bermudez, Joyce C. Harper, Dagan Wells, (2003) Detailed investigation of factors influencing amplification efficiency and allele dropout in single cell PCR: implications for preimplantation genetic diagnosis, Molecular Human Reproduction, 9, 411-420
M. Simopoulou, J. C. Harper, E. Fragouli, A. Mantzouratou, B. E. Speyer, P. Serhal, D. M. Ranieri, A. Doshi, J. Henderson, C. H. Rodeck and J. D. A. Delhanty, (2003) Preimplantation Genetic Diagnosis of Chromosome Abnormalities: Implications from the Outcome for Couples with Chromosomal Rearrangements. Prenatal Diagnosis, 652-662
Daphnis, D, Jerkovic, S, Geyer, J, Craft, I, Delhanty,, JDA, Harper, JC (2005) Detailed FISH analysis of day 5 human embryos reveals the mechanisms leading to mosaic aneuploidy, Human Reproduction, 20, 129-137
Fragouli, E, Wells, D, Doshi, A, Gotts, S, Harper, JC, Delhanty , JDA (2006). Complete cytogenetic investigation of oocytes from a cancer patient with the use of comparative genomic hybridisation reveals meiotic errors. Prenat Diagn, 26, 71-7

Other Publications

Yang, D., and Harper, J. (1992) Capacitated or acrosome-reacted sperm? Fert. and Stert. 58 860-861
Verlinsky, Y., Handyside, AH., Grifo, J., Munne, S., Cohen, J., Liebers, I., Levinson, G., Arnheim, N., Hughes, M., Delhanty, J., Harper, J., Mathews, C., Kuliev, A., Simpson, JL., Monk, M., Strom, C., Findlay, I., Gore-Langhton, R., Lansendorf, S., Braude, P., Muggleton-Harris, A., Lissens, W., Ginsberg, N., Jackson, L., Gitlin, S., Fisher., J. Readhead, C., Wilton, L., De Sutter, P., Selva, J., Ray, P., Thornhill, A., Kontogianni, E., Johnson, M. (1994) Preimplantation Diagnosis of Genetic and chromosomal disorders. J. Ass. Reprod. Genet 11 236-243.
Harper, J, Griffin, D, Wells, D., Handyside, A.H., Winston, R., and Delhanty, JDA. (1994) The use of FISH for genetic diagnosis and analysis of human preimplantation embryos. Proceedings of 7th International Conference on Early Prenatal Diagnosis, Monduzzi Editore, Ed. Haim Zakut, 141-146
Harper, J.C. (1995) Review of The 7th International Conference on Early Prenatal Diagnosis: Some personal impressions. Prenatal Diagnosis 15, 401-406
Delhanty, JDA, Wells, D., and Harper, JC (1997) Editorial - Diagnosis before implantation. BMJ 315, 828-829.
Harper, JC, Delhanty, JD and Pergament, E (1998) Editorial - Special issue of Prenatal Diagnosis - Preimplantation Genetics and Diagnosis.
Harper, JC, Delhanty, JD and Pergament, E (1999) Editorial - Special issue of Prenatal Diagnosis - Preimplantation Genetics and Diagnosis.
ESHRE Preimplantation Genetic Diagnosis (PGD) Consortium (1999). Preliminary assessment of data from January 1997 to September 1998 ESHRE PGD Consortium Steering Committee. Human Reproduction, ; 14: 3138-3148.
ESHRE PGD Consortium Steering Committee (2000) ESHRE Preimplantation Genetic Diagnosis (PGD) Consortium: data collection II (May 2000). Hum. Reprod. 15, 2673-2683.
Joep P.M.Geraedts, Joyce Harper, Peter Braude, Karen Sermon, Anna Veiga, Luca Gianaroli, Noelle Agan, Santiago Munné, Sue Gitlin, Elisabeth Blenow, Kylie de Boer, Nicole Hussey, Emmanuel Kanavakis,Soo-Huan Lee, Stéphane Viville, Lewis Krey, Pierre Ray, Serena Emiliani, Yung Hsien Liu, Stefan Vermeulen. (2001) Preimplantation Genetic Diagnosis (PGD), a collaborative activity of clinical genetic departments and IVF centres. Prenatal Diagnosis, 21: 1086-1092
ESHRE PGD Consortium Steering Committee (2002) ESHRE Preimplantation Genetic Diagnosis (PGD) Consortium: data collection III (May 2001), Hum Reprod., 17, 233-246.
Harper, JC, Pergament, E, Delhanty, JDA (2004) Genetics of gametes and embryos. European Journal of Obstetrics & Gynaecology and Reproductive Biology, 115, S80-S84
Sermon, K., Moutou, C., Harper, J., Geraedts, J., Scriven, P., Wilton, L., Magli, M.-C., Michiels A, Viville, S., De Die, C. (2005) ESHRE PGD Consortium data collection IV: May-December 2001, Human Reproduction, 20(1):19-34.
Thornhill , AR, deDie-Smulders, CE, Geraedts, JP, Harper, JC, Harton, GL, Lavery, SA, Moutou, C, Robinson, MD, Schmutzler, AG, Scriven, PN, Sermon, KD, Wilton, L (2005) ESHRE PGD Consortium Best Practice Guidelines for Clinical Preimplantation Genetic Diagnosis (PGD) and Preimplantation Genetic screening (PGS), Human Reproduction, 20 (1):35-48.
Harper, J.C, Boelaert, K, Geraedts, J., Harton, G., Kearns, WG, Moutou, C., Muntjewerff, N., Repping, S, SenGupta, S, Scriven, P.N., Traeger-Synodinos, J, Vesela, K, Wilton, L, Sermon, K.D. (2006) ESHRE PGD Consortium data collection V: Cycles from January to December 2002 with pregnancy follow-up to October 2003, Human Reproduction, 21, 3-21
Soini S, Ibarreta D, Anastasiadou V, Ayme S, Braga S, Cornel M, Coviello DA, Evers-Kiebooms G, Geraedts J, Gianaroli L, Harper J, Kosztolanyi G, Lundin K, Rodrigues-Cerezo E, Sermon K, Sequeiros J, Tranebjaerg L, Kaariainen H., (2006) The interface between assisted reproductive technologies and genetics: technical, social, ethical and legal issues. European Journal Human Genetics, 14, 588-645.
Sermon, K.D, Michiels, A, Harton, G, Moutou, C, Repping, S, Scriven, P.N, SenGupta, S,Traeger-Synodinos, J, Vesela, K, Viville, S, Wilton, L, Harper, J.C (2006) ESHRE PGD Consortium data collection VI: Cycles from January to December 2003 with pregnancy follow-up to October 2004, Human Reproduction, in press

Reviews

Lea, R.G., Harper, J.C., Banwatt, D., Manuel, J., Daya, S., Porat, O., Craft, I.L., and Clark, D.A. (1991) Is there an early embryo associated suppressor factor. In Cellular and Molecular Biology of Materno-fetal relationships. Eds. Chaouat, John Mowbray 212 161-168
Harper, J.C., and Handyside, A.H. (1994) The current status of preimplantation diagnosis. Current Obs and Gynae. 4, 143-149
Harper, JC (1996) Preimplantation diagnosis of inherited disease by embryo biopsy. An update of the world figures. J. Assit Reprod. Genet. 13(2)90-94
Harper JC and Delhanty, JDA (2000), Preimplantation Genetic Diagnosis, Current Opinions in Obstetrics and Gynaecology. Apr;12(2):67-72
Harper JC and Rodeck, C (2002) Preimplantation Genetic Diagnosis, Progress in Obstetrics and Gynaecology, Volume 15, 33-43
Delhanty, JDA and Harper, JC (2002) Preimplantation Genetic Diagnosis, Reproductive Medicine Review, 10 (1), 1-19
Bui, TH and Harper, JC (2002) Preimplantation Genetic Diagnosis, Clinical Obstetrics and Gynaecology, 45 (3) 1-9