Case Studies in Assisted Reproduction

Case Studies in Assisted Reproduction Common and Uncommon Presentations

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Case Studies in Assisted Reproduction Common and Uncommon Presentations Nick S. Macklon University of Southampton, UK

Human M. Fatemi The Centre for Reproductive Medicine, NOVA-IVI Fertility, Abu Dhabi/UAE

Robert J. Norman The University of Adelaide, Australia

Pasquale Patrizio Yale School of Medicine, New Haven, CT, USA






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Library of Congress Cataloguing in Publication data Case studies in assisted reproduction : common and uncommon presentations / [edited by] Nick S. Macklon, Human M. Fatemi, Robert J. Norman, Pasquale Patrizio. p. ; cm. Includes bibliographical references and index. ISBN 978-1-107-66457-9 (paperback) I. Macklon, Nick S., editor. II. Fatemi, Human M., editor. III. Norman, Robert (Robert J.), editor. IV. Patrizio, Pasquale., editor. [DNLM: 1. Reproductive Techniques, Assisted–Case Reports. 2. Genital Diseases, Female–complications–Case Reports. 3. Genital Diseases, Male–complications–Case Reports. 4. Infertility–Case Reports. WQ 208] RG133.5 618.1′78–dc23 2014036818

ISBN 978-1-107-66457-9 Paperback

Cambridge University Press has no responsibility for the persistence or accuracy of URLs for external or third-party internet websites referred to in this publication, and does not guarantee that any content on such websites is, or will remain, accurate or appropriate.

Every eff ort has been made in preparing this book to provide accurate and up-to-date information which is in accord with accepted standards and practice at the time of publication. Although case histories are drawn from actual cases, every eff ort has been made to disguise the identities of the individuals involved. Nevertheless, the authors, editors and publishers can make no warranties that the information contained herein is totally free from error, not least because clinical standards are constantly changing through research and regulation. Th e authors, editors and publishers therefore disclaim all liability for direct or consequential damages resulting from the use of material contained in this book. Readers are strongly advised to pay careful attention to information provided by the manufacturer of any drugs or equipment that they plan to use.






v

1. Type 2 diabetes mellitus 1 Catherine Henry and William M. Hague

2. A woman with hypertension 7 Mark R. Morton and William M. Hague

3. Increased risk of venous thromboembolism (VTE) 12 Nick S. Macklon

4. Assisted reproduction in a subfertile couple with serodiscordant HIV infection 16 S. McDowell, B. Kroon, and A. Yazdani

5. A woman with renal impairment 19 Shilpa Jesudason and William M. Hague

6. A male with oligozoospermia and muscle weakness subsequently diagnosed with myotonic dystrophy 24 Inge Liebaers and Willem Verpoest

7. Never say never to a Klinefelter patient 27 Inge Liebaers and Herman Tournaye

8. A man with retrograde ejaculation 30 S. Alberto D á vila Garza and Pasquale Patrizio

9. A patient with severe lupus 33 Erin Clark and William M. Hague

10. One partner is a carrier of thalassemia, one a carrier of sickle cell anemia 38 Human M. Fatemi

11. A patient with Kallmann syndrome 41 Dimitra Kyrou

12. A patient with severe endometriosis needing IVF 43 Luk Rombauts, Sameer Jatkar, Sofi e Piessens, and Peter Carne

13. Recurrent miscarriage due to a balanced translocation: a case of PGS 46 Michael J. Paidas and S. Ornaghi

14. A patient found to have Cushing syndrome 50 Sunita De Sousa and Robert J. Norman

15. Postpartum pituitary problems 53 Tristan Hardy and Robert J. Norman

16. Large bilateral endometriomas 56 Juan A. Garcia-Velasco and Israel Ortega

17. A patient with a thin endometrium 60 Dimitra Kyrou

18. A poor responder 63 Katrina Rowan

19. Recurrent implantation failure 67 P. Donoso and P. Sanhueza

Contents

List of contributors ix Preface xv List of abbreviations xvii






Contentsvi

20. Fertility preservation in an adolescent with Turner syndrome 70 Michel De Vos

21. A young woman with a low AMH 73 Christophe Blockeel and Veerle Vloeberghs

22. The patient who bleeds in the early luteal phase 75 Robert Lahoud and Manveen (Manny) Mangat

23. Threatened OHSS in a long GnRH agonist protocol 80 E. Papanikolaou

24. An endometrial polyp detected during ovarian stimulation for IVF 82 Human M. Fatemi and Biljana Popovic Todorovic

25. Fluid in the endometrial cavity during IVF treatment 85 Carolien M. Boomsma and Nick S. Macklon

26. Tubal embryo transfer: a novel approach to manage diffi cult uterine access 90 Andrew Murray and John Hutton

27. Mild-approach ART in a patient with polycystic ovary syndrome 93 Michel De Vos

28. A slim patient with polycystic ovary syndrome (PCOS) 97 Robert Lahoud, Manveen (Manny) Mangat, and Cherise Mooy

29. Recurrent cycles with retrieval of immature germinal vesicle (GV) oocytes 102 Sonal Karia, Mark Bowman, and Derek Lok

30. Think heterotopic pregnancy 105 Amanda Kallen and Pasquale Patrizio

31. A woman with a hydrosalpinx 108 Biljana Popovic Todorovic and Gordana Ivanovic

32. A PCOS patient with microprolactinoma, autoimmune thyroid disease, and congenital thrombophilia 111 Biljana Popovic Todorovic and Jelena Todorovic

33. IVF outcome in the same patient before and after myomectomy 115 Hammed A. Tijani and Ying Cheong

34. A patient with factor XI defi ciency and immune thrombocytopenia 118 Hammed A. Tijani and Ying Cheong

35. Abnormal cavity; abnormal fertility? 121 Jenneke C. Kasius

36. A male partner with ’fl u 124 Elisabeth Carlsen

37. Selecting the day of triggering fi nal oocyte maturation when follicle growth is asynchronous 127 E. Papanikolaou

38. Late-onset ovarian hyperstimulation syndrome (OHSS) 129 Leo Doherty and Saioa Torrealday

39. The patient with recurrent poor embryo quality 133 Cindy M. P. Duke and Pasquale Patrizio

40. A high progesterone level during ovarian stimulation 137 Christophe Blockeel and Herman Tournaye






Contents vii

41. Repeated fertilization failure with normal sperm and MII oocytes 140 Denny Sakkas and Steven Bayer

42. A complete uterine septum: to treat or not to treat? 145 Jenneke C. Kasius

43. Endometritis detected prior to IVF 148 Jenneke C. Kasius

44. LH rise on the day of GnRH antagonist commencement 151 Human M. Fatemi and Biljana Popovic Todorovic

45. Controlled ovarian stimulation (COS) in a woman with normal ovarian reserve 154 Shane T. Lipskind and Elizabeth S. Ginsburg

46. Errors in dosing medications 158 Saioa Torrealday and Leo Doherty

47. Monozygotic triplets after single embryo transfer 163 Luk Rombauts, Sameer Jatkar, and Mark Teoh

48. A teenager facing total body irradiation 167 Kirsten Tryde Schmidt

49. A 30-year-old woman with breast cancer 170 Katrina Rowan

50. A spontaneous pregnancy in Turner syndrome 174 Outi Hovatta and Birgit Borgstr ö m

51. Fertility after conservative surgery for recurrent borderline ovarian tumor 177 Luk Rombauts, Sameer Jatkar, and Tom Manolitsas

52. Successful pregnancy after radical trachelectomy and McDonald cerclage placement in a 42-year-old with invasive cervical adenocarcinoma 180 Jonathan D. Black and Masoud Azodi

53. Childbearing after conservative management of endometrial cancer 183 Jen-Ruei Chen and Masoud Azodi

54. Fertility preservation in a female of reproductive age with ovarian cancer 187 Jen-Ruei Chen and Masoud Azodi

55. Mother daughter triplet surrogacy: the f irst reported case 192 Joel Bernstein

56. Known sperm donation: helping siblings in family building 195 Patricia Baetens and Herman Tournaye

57. A 5-year-old with pelvic rhabdomyosarcoma 199 Alison Fernbach and Jennifer Levine

58. Co-fatherhood: same-sex male couple and IVF 202 Saioa Torrealday and Dorothy A. Greenfeld

59. Sensorineural hearing loss following ovarian stimulation 206 Bala Karunakaran, Nicholas Brook, Daniel Hajioff , Geoff rey Trew, and Th eo Joseph

Index 209











ix

Contributors

Masoud Azodi Department of OB/GYN and Reproductive Sciences, Gynecologic Oncology Section, Yale University School of Medicine, New Haven, CT, USA

Patricia Baetens Psychologist at the Centre for Reproductive Medicine at the Universitair Ziekenhuis Brussel (UZ Brussel) Brussels, Belgium

Steven Bayer Boston IVF Inc., Waltham, MA, USA

Joel Bernstein Medical Director at Fertility East, Sydney, NSW, Australia

Jonathan D. Black Physician, Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, CT, USA

Christophe Blockeel Medical director/gynecologist at the Centre for Reproductive Medicine at Universitair Ziekenhuis Brussel (UZ Brussel), Brussels, Belgium

Carolien M. Boomsma Specialist training fellow in Obstetrics and Gynecology, University Medical Center Utrecht, Th e Netherlands

Birgit Borgstr ö m Department of Pediatrics, Karolinska Institute, Stockholm, Sweden

Mark Bowman Fertility Specialist, Genea, NSW, Australia

Nicholas Brook Complete Fertility Centre, University Hospitals Southampton NHS Foundation Trust, Southampton, UK

Elisabeth Carlsen Th e Fertility Clinic, Copenhagen University Hospital, Denmark

Peter Carne Colorectal Surgeon, Cabrini and Alfred Hospitals; Senior Lecturer, Cabrini Monash University Department of Surgery, VIC, Australia

Ying Cheong Associate Professor of Obstetrics and Gynaecology, University of Southampton, and Clinical Director, Complete Fertility Centre, Southampton, UK

Jen-Ruei Chen Division of Gynecologic Oncology, Department of OB/GYN, Mackay Memorial Hospital, Taipei, and Mackay Medicine, Nursing and Management College, Taipei, Taiwan, ROC

Erin Clark Consultant Physician in Obstetric Medicine, Women’s and Children’s Hospital, Adelaide, SA, Australia

S. Alberto D á vila Garza Instituto para el Estudio de la Concepci ó n Humana, IECH, Monterrey, Mexico

Sunita De Sousa Endocrine Fellow, University of Adelaide School of Medicine, Adelaide, SA, South Australia






List of contributorsx

Michel De Vos Medical director/gynecologist at the Center for Reproductive Medicine, Universitair Ziekenhuis Brussel (UZ Brussel), Brussels, Belgium

Leo Doherty IVF New Jersey, Somerset, NJ, USA

Patricio Donoso Reproductive Medicine Unit, Clinica Alemana, Vitacura 5951, Santiago, Chile

Cindy M. P. Duke Clinical Instructor, Reproductive Endocrinology & Infertility, Department. of Obstetrics and Gynecology, Yale University School of Medicine, New Haven, CT, USA

Human M. Fatemi Professor of Reproductive Medicine at the Centre for Reproductive Medicine, NOVA-IVI Fertility, Abu Dhabi/UAE

Alison Fernbach Pediatric Nurse Practitioner, Division of Pediatric Hematology/Oncology/Stem cell transplantation, Morgan Stanley Children’s Hospital of New York-Presbyterian, Columbia University Medical Center, NY, USA

Juan A. Garcia-Velasco Professor of Obstetrics and Gynecology, IVI-Madrid, Rey Juan Carlos University, Madrid, Spain

Elizabeth S. Ginsburg Medical Director of the In Vitro Fertilization Program at Brigham & Women’s Hospital, and an Associate Professor of Obstetrics, Gynecology and Reproductive Biology at Harvard Medical School, MA, USA

Dorothy A. Greenfeld Department of Obstetrics, Gynecology and Reproductive Science, Yale University School of Medicine, New Haven, CT, USA

William M. Hague Professor – Robinson Research Institute; Professor of Obstetric Medicine, School of Paediatrics and Reproductive Health, University of Adelaide; Senior Consultant Physician in Obstetric Medicine, Women & Children’s Hospital, Adelaide, SA, Australia

Daniel Hajioff North Bristol NHS Trust, Bristol, UK

Tristan Hardy Obstetric and Gynecology fellow, Royal Hospital for Women, University of New South Wales, Sydney, Australia

Catherine Henry Trainee in Internal Medicine, Royal Adelaide Hospital, Adelaide, SA, Australia

Outi Hovatta Senior professor of Obstetrics, Department of Obstetrics and Gynecology, Karolinska Institute, Stockholm, Sweden

John Hutton Professor of Reproductive Endocrinology and Infertility, University of Otago, Wellington, New Zealand

Gordana Ivanovic Special Gynecological Hospital ‘Ivanovic’ Belgrade, Serbia

Sameer Jatkar Fellow in Reproductive Medicine, Monash IVF, Richmond, VIC, Australia

Shilpa Jesudason Consultant physician, Renal Medicine, Central and Northern Adelaide Renal and Transplantation Service, Th e Royal Adelaide Hospital, Adelaide, SA, Australia

Theo Joseph Royal National Th roat, Nose and Ear Hospital, London, UK






List of contributors xi

Amanda Kallen Assistant Professor, Obstetrics, Gynecology, and Reproductive Sciences at the Department of Obstetrics, Gynecology & Reproductive Sciences, Yale School of Medicine, New Haven, CT, USA

Sonal Karia Fertility Specialist, Genea, NSW, Australia

Bala Karunakaran University Hospitals Southampton NHS Foundation Trust, Southampton,UK

Jenneke C. Kasius Department of Reproductive Medicine and Gynecology, University Medical Center Utrecht, Utrecht, Th e Netherlands.

Ben Kroon Queensland Fertility Group Research Foundation and the University of Queensland, Queensland, Australia

Dimitra Kyrou Specialist in Reproductive Medicine, Clinical Director of Assisted Reproduction Unit ‘Assisting Nature’, Th essaloniki, Greece

Robert Lahoud Clinical Director, IVFAustralia, Castle Hill, NSW, Australia

Jennifer M Levine Medical Director, Center for Survivor Wellness, Assistant Professor of Pediatrics at Columbia University Medical Center Division of Hematology, Oncology and Stem Cell Transplant

Inge Liebaers Emeritus professor in medical genetics, former Director of the Center for Medical Genetics, Vrije Universiteit Brussels, Brussels, Belgium

Shane T. Lipskind Arizona Center for Fertility Studies, Scottsdale, Arizona, USA

Derek Lok Fertility Specialist, Genea, NSW, Australia

Nick S. Macklon Professor of Obstetrics and Gynaecology, University of Southampton, UK

Manveen (Manny) Mangat Specialist in Infertility & IVF, Laparoscopic Surgery, Male Infertility and Gynecology, North Shore Specialist Day Hospital, North Shore Private and Mater Private, and IVFAustralia’s City and Northshore clinics, Sydney, NSW, Australia

Tom P. Manolitsas Gynecologist, Epworth Eastern Hospital, Box Hill, VIC, Australia

S. McDowell Queensland Fertility Group Research Foundation and University of Queensland, Queensland, Australia

Cherise Mooy Senior embryologist, IVFAustralia, Sydney, NSW, Australia

Mark R. Morton Senior consultant physician in Obstetric Medicine, Women’s and Children’s Hospital, North Adelaide, SA, Australia

Andrew Murray Medial Director, Fertility Associates, Wellington; Senior Lecturer, Otago School of Medicine, Wellington, New Zealand

Robert J. Norman Professor of Reproductive and Periconceptual Medicine, Robinson Research Institute, Department of Obstetrics & Gynecology, University of Adelaide, SA, Australia

Sara Ornaghi Department of Obstetrics and Gynecology, University of Milna-Bicocca and San Gerardo Hospital, Monza, Italy






List of contributorsxii

Israel Ortega IVI-Madrid, Rey Juan Carlos University, Madrid, Spain

Michael J. Paidas Professor of Obstetrics, Gynecology, and Reproductive Sciences, Co-Director, Yale Women and Children’s Center for Blood Disorders and Co-Director at the National Hemophilia Foundation-Baxter Clinical Fellowship at Yale School of Medicine, New Haven, CT, USA

Evaggelos Papanikolaou Director, Human Reproduction and Genetics Foundation, Th essaloniki, Greece

Pasquale Patrizio Professor of Obstetrics and Gynecology and Director, Yale Fertility Center, Yale University School of Medicine, New Haven, CT, USA

Sofi e Piessens Camberwell Ultrasound for Women, Hawthorn East, and Central Ultrasound for Women, Fitzroy, VIC, Australia

Biljana Popovic Todorovic Fertility specialist at IVF Center “Ivanovic”, Belgrade, Serbia

Luk Rombauts Adjunct Clinical Associate Professor in the Department of Obstetrics and Gynecology at Monash University and the Head of Reproductive Medicine at Monash Medical Centre, Southern Health, Melbourne,VIC, Australia

Katrina Rowan Fertility specialist, Genea, NSW, Australia

Denny Sakkas Boston IVF Inc., Waltham, MA, USA

P. Sanhueza Reproductive Medicine Unit, Clinica Alemana, Vitacura 5951, Santiago, Chile

Kirsten Tryde Schmidt Consultant Gynecologist, Fertility Clinic, University Hospital of Copenhagen (Rigshospitalet), Copenhagen, Denmark

Mark Teoh Camberwell Ultrasound for Women, Hawthorn East, and Central Ultrasound for Women, Fitzroy, VIC, Australia

Hammed A. Tijani Senior Special Interest Training Fellow, Obstetrics and Gynecology Department, University Hospitals Southampton NHS, Southampton, UK.

Jelena Todorovic Fertility specialist at IVF Center “Ivanovic”, Belgrade, Serbia

Saioa Torrealday Clinical Instructor, Department of Obstetrics, Gynecology and Reproductive Science, Yale University School of Medicine, New Haven, CT, USA

Herman Tournaye Professor in Reproductive Medicine, Developmental Biology and Embryology at Vrije Universiteit Brussel and Director of the Center for Reproductive Medicine at Universitair Ziekenhuis Brussel (UZ Brussel), Brussels, Belgium

Geoff rey Trew Institute of Reproductive and Developmental Biology, Hammersmith Hospital, London, UK

W. Verpoest Medical Director/gynaecologist at the Centre for Reproductive Medicine at Universitair Ziekenhuis Brussel (UZ Brussel), Brussels, Belgium






List of contributors xiii

Veerle Vloeberghs Resident gynecologist at the Center for Reproductive Medicine at Universitair Ziekenhuis Brussel (UZ Brussel), Brussels, Belgium

A. Yazdani Queensland Fertility Group Research Foundation and University of Queensland, Queensland, Australia











xv

As the range of indications for assisted conception expands and the number and complex-ity of treatment options available rise, busy clinicians require ready access to information which can guide the management of their patients. Case histories rarely appear now in international journals, but they can serve a very valuable role to illustrate key concepts and options for managing diffi cult clinical situations in practice.

For this book, four internationally recognized experts in Reproductive Endocrinology and Infertility Medicine have gathered a series of case histories which represent a compre-hensive view of the clinical challenges faced in contemporary practice. Written by experi-enced practicing clinicians, each case describes common and less common presentations, their investigation and management, and also provides the authors’ personal refl ection on the case and suggested references for further reading.

We thank all the contributors to this book and we hope that our colleagues will fi nd it to be a useful resource.

Preface











xvii

Abbreviations

ACE angiotensin-converting enzyme ACTH adrenocorticotropic hormone AFP alpha-fetoprotein AI artifi cial insemination AITD autoimmune thyroid disease ALT alanine aminotransferase AMH antim ü llerian hormone ANA antinuclear antibody APTT activated partial thromboplastin time ARDS acute respiratory distress syndrome ART assisted reproductive technology/technologies; assisted

reproduction treatment ASFC antral follicle count ASRM American Society for Reproductive Medicine AST aspartate aminotransferase (SGOT) BEP regimen bleomycin, etoposide(VP-16), and cisplatin BHCG beta-hCG BMI body mass index BP blood pressure CBC complete blood count CEA carcinoembryonic antigen CGH comparative genomic hybridization CHB congenital heart block CHIPS the Control of Hypertension in Pregnancy Study CI confi dence interval CIN cervical intraepithelial neoplasia CKD chronic kidney disease CMP complete metabolic panel CMV cytomegalovirus COC cumulus–oocyte complex COH controlled ovarian hyperstimulation COS controlled ovarian stimulation CRH corticotropin-releasing hormone CT computed tomography D&C dilatation and curettage DHEAS dehydroepiandrosterone sulfate DIE deep infi ltrating endometriosis DVT deep vein thrombosis E2 estradiol






List of abbreviationsxviii

ECG electorcardiography/electorcardiogram (e)GFR (estimated) glomerular fi ltration rate ENA extractable nuclear antigen ER estrogen receptor ESHRE European Society of Human Reproduction and Embryology FAI Free Androgen Index FEC-D 5-fl uorouracil–epirubicin–cyclophosphamide followed by doc-

etaxel FET frozen embryo transfer cycles FFP fresh frozen plasma FIGO International Federation of Gynecology and Obstetrics FSH follicle-stimulating hormone FT4 free thyroxine FXI factor XI G-CSF granulocyte colony-stimulating factor GCT glucose challenge test GDM gestational diabetes mellitus GIFT gamete intrafallopian (tube) transfer GnRH (GnRHa) gonadotropin-releasing hormone (agonist) GV germinal vesicle HA hyaluronic acid hCG human chorionic gonadotropin HCV hepatitis C virus HGH human growth hormone HIV human immunodefi ciency virus hMG/HMG human menopausal gonadotropin HOS hypo-osmotic swelling HP-HMG highly purifi ed human menopausal gonadotrophin HP-hMG high-purity human menopausal gonadotropin HRT hormone replacement therapy HSG hysterosalpingogram/hysterosalpingography HTLV human T-lymphotropic virus Hycosy hysterosalpingo-contrast sonography ICSI intracytoplasmic sperm injection IGF1 insulin-like growth factor 1 IM intramuscular(ly) IMSI intracytoplasmic morphologically selected sperm injection INR international normalized ratio ITP immune thrombocytopenia IUI intrauterine insemination IVF in vitro fertilization IVIG intravenous immunoglobulin IVM in vitro maturation LDH lactate dehydrogenase LDR long down-regulation (protocol)






List of abbreviations xix

LH luteinizing hormone LLETZ large loop excisions of transformation zone LMP low malignant potential LMWH low-molecular-weight heparin MFM maternal fetal medicine MPA medroxyprogesterone acetate MRI magnetic resonance imaging MTHFR methylene-tetrahydrofolate reductase NNT number needed to treat NSAID nonsteroidal anti-infl ammatory drug OCP oral contraceptive pill OHSS ovarian hyperstimulation syndrome OPU ovum pick-up OR odds ratio PCO polycystic ovary PCOS polycystic ovary syndrome PCR protein/creatinine ratio PGD preimplantation genetic diagnosis PGS preimplantation genetic screening PI pulsatility index PO by mouth; orally POI premature ovarian insuffi ciency PPROM preterm premature rupture of membranes PR progesterone receptor PRL prolactin PT prothrombin time PTT partial thromboplastin time RCT randomized controlled trial rFSH, rec-FSH, rh-FSH recombinant (human) follicle-stimulating hormone RI resistance index RR relative risk SC subcutaneous(ly) SCD sperm chromatin dispersion (test) SCSA sperm chromatin structure assay SGM surrogate gestational mother SHBG sex hormone-binding globulin SHG sonohysterogram SLE systemic lupus erythematosus SSRI selective serotonin reuptake inhibitor STD sexually transmitted disease T2DM type 2 diabetes mellitus TG thyroglobulin TPO thyroid peroxidase TSH thyroid-stimulating hormone TVS transvaginal sonography






List of abbreviationsxx

USS ultrasound scan VDRL Venereal Disease Research Laboratory (test for syphilis) VEGF vascular endothelial growth factor VTE venous thromboembolism (VTE) WBC white blood cell (count)






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Case Studies in Assisted Reproduction