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Unexplained Infertility View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Helsingin yliopiston digitaalinen arkisto Department of Obstetrics and Gynaecology, Helsinki University Central Hospital, University of Helsinki, Finland UNEXPLAINED INFERTILITY Studies on aetiology, treatment options and obstetric outcome RITA ISAKSSON ACADEMIC DISSERTATION To be presented by permission of the Medical Faculty of the University of Helsinki for public criticism in the Auditorium of the Department of Obstetrics and Gynaecology, Helsinki University Central Hospital, Haartmaninkatu 2, Helsinki, on October 18th, 2002, at 12 noon. Helsinki 2002 1 Supervised by Docent Aila Tiitinen, M.D., Ph.D. Department of Obstetrics and Gynaecology Helsinki University Central Hospital Docent Bruno Cacciatore, M.D., Ph.D. Department of Obstetrics and Gynaecology Helsinki University Central Hospital Reviewed by Docent Anne-Maria Suikkari, M.D., Ph.D. The Family Federation of Finland, Infertility Clinic, Helsinki Docent Aydin Tekay, M.D., Ph.D. Department of Obstetrics and Gynaecology Oulu University Central Hospital Offi cial opponent Docent Hannu Martikainen, M.D., Ph.D. Department of Obstetrics and Gynaecology Oulu University Central Hospital ISBN 952-91-5071-7 (print) ISBN 952-10-0712-5 (PDF) Yliopistopaino Helsinki 2002 2 To my family 3 CONTENTS LIST OF ORIGINAL PUBLICATIONS ....................................................................7 ABBREVIATIONS .................................................................................................. 8 ABSTRACT ............................................................................................................. 9 I INTRODUCTION .............................................................................................. 11 II REVIEW OF THE LITERATURE 1. Infertility ................................................................................................. 12 2. Unexplained infertility ............................................................................ 13 2.1. Defi nition and incidence ............................................................ 13 2.2. Speculations on possible underlying causes ...............................14 2.3. Treatment options ...................................................................... 17 3. Ultrasound examination .......................................................................... 20 3.1. Basic ........................................................................................... 20 3.2. Doppler ultrasound .................................................................... 21 3.3. Doppler ultrasound during natural and IVF cycles .................... 22 4. Assisted reproductive technology ........................................................... 28 4.1. Defi nition and rate of success .................................................... 28 4.2. Prognostic markers for successful outcome .............................. 31 4.3. Pregnancy outcome of ART-induced pregnancies ...................... 35 III AIMS OF THE STUDY ................................................................................... 41 IV PATIENTS AND METHODS ........................................................................... 42 1. Study populations and protocols ............................................................ 42 Study I ............................................................................................... 43 Study II ...............................................................................................43 Studies III and IV ............................................................................... 44 Study V .............................................................................................. 44 2. Hormonal assays ...................................................................................... 47 3. Ultrasound and Doppler assessment ....................................................... 47 4. Statistical analysis .................................................................................... 48 V RESULTS .......................................................................................................... 49 1. Uterine and spiral artery blood fl ow in unexplained infertility .............. 49 2. Prognostic signifi cance of uterine artery impedance ............................. 50 3. Comparison of ovulation induction combined with intra-uterine insemination, intraperitoneal insemination and timed intercourse ......... 50 4. Course of ART-induced and spontaneous pregnancies ........................... 52 VI DISCUSSION .................................................................................................. 55 1. Uterine and spiral artery impedance among women with unexplained infertility ............................................................................ 55 2. Prediction of pregnancy outcome with uterine artery impedance measurement ...................................................................... 57 3. Treatment options of women with unexplained infertility ..................... 58 4. Long-term prognosis of couples with unexplained infertility ................. 59 5. Obstetric outcome of couples with unexplained infertility ................... 60 VII SUMMARY AND CONCLUSIONS ................................................................ 62 ACKNOWLEDGEMENTS .................................................................................... 63 REFERENCES ...................................................................................................... 65 LIST OF ORIGINAL PUBLICATIONS I. Isaksson R, Tiitinen A, Reinikainen L and Cacciatore B. Comparison of the uterine and spiral artery blood fl ow in women with unexplained and tubal infertility. Ultrasound Obstet Gynecol, in press. II. Isaksson R, Tiitinen A and Cacciatore B. Uterine artery impedance to blood fl ow on the day of embryo transfer does not predict obstetric outcome. Ultrasound Obstet Gynecol 2000; 15: 527-530. III. Isaksson R and Tiitinen A. Superovulation combined with insemination or intercourse in the treatment of couples with unexplained infertility and minimal endometriosis. Acta Obstet Gynecol Scand 1997; 76: 550-554. IV. Isaksson R and Tiitinen A. Obstetric outcome in patients with unexplained infertility: Comparison of treatment-related and spontaneous pregnancies. Acta Obstet Gynecol Scand 1998; 77: 849-853. V. Isaksson R, Gissler M and Tiitinen A. Obstetric outcome among women with unexplained infertility after IVF: a matched case-control study. Hum Reprod 2002; 17: 1755-1761. The orginal Publications are reproduced with permission of the copyright holders. 7 ABBREVIATIONS ART assisted reproductive technology CC clomiphene citrate COH controlled ovarian hyperstimulation CV coeffi cient of variation DIPI direct intraperitoneal insemination ET embryo transfer FSH follicle-stimulating hormone GIFT gamete intra-fallopian transfer GnRHa gonadotrophin-releasing hormone agonist hCG human chorionic gonadotrophin hMG human menopausal gonadotrophin HSG hysterosalpingography HSSG hysterosalpingosonography ICD international classifi cation of diseases ICSI intracytoplasmic sperm injection im intramuscular IU international unit IUI intra-uterine insemination IUGR intra-uterine growth retardation IVF in-vitro fertilization LH luteinizing hormone Mhz megahertz MBR Medical Birth Register OPU ovum pick-up PIH pregnancy-induced hypertension PI pulsatility index PSV peak systolic velocity RI resistance index sc subcutaneous SE standard error of mean SD standard deviation SGA small for gestational age SPSS statistical package for social sciences TI timed intercourse US ultrasound WHO World Health Organization ZIFT zygote intra-fallopian transfer 8 ABSTRACT Unexplained infertility, refering to the failure to conceive of a couple in whom no defi nitive cause for infertility can be found, has an incidence of 10-20% in all infertile couples. The purpose of this study was to examine the impedance to uterine blood fl ow, different treatments and obstetric outcome in unexplained infertility. Main uterine and spiral artery impedance to blood fl ow was compared in 20 women with unexplained and 18 women with tubal infertility. Measurements were taken both during the natural cycle (on days 11-12, 16-17 and 21-23) and during the in-vitro fertilization (IVF) treatment cycle (on days 1, 5, 10, ovum pick-up and embryo transfer). The mean uterine artery impedance was below three in women with unexplained infertility during the natural and IVF cycles, and no signifi cant differences were observed between the groups. The mean impedance (± SD) in spiral arteareries was lower (pulsatility index 0.96 ± 0.25) in women with unexplained infertility on day 5 of gonadotrophin stimulation compared with women with tubal infertility (pulsatility index 1.24 ± 0.30; p<0.05). The main uterine artery impedance to blood fl ow was studied among 102 women during 111 conceptional IVF cycles. The aetiology of infertility was either unexplained, tubal, endometriosis or multifactorial. Predicting obstetric complications with measurement of uterine artery impedance among these women was not possible. The mean uterine artery pulsatility index (PI) was comparable in pregnancies leading to spontaneous abortion (PI 2.71 ± 0.67), ectopic pregnancy (PI 2.36 ± 0.54) and normal intra-uterine pregnancy (PI 2.69 ± 0.71). Seventy women with unexplained infertility were treated with ovulation induction combined with intra-uterine insemination, direct intraperitoneal
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