Đang tải... (xem toàn văn)
(BQ) Part 1 book “Infertility in practice” has contents: Infertility – Epidemiology, diagnosis and counselling, prevention of infertility, investigating infertility, anovulatory infertility and ovulation induction, polycystic ovary syndrome, premature ovarian insufficiency (failure) and oocyte donation,…. And other contents.
RepRoductive Medicine & Assisted RM&ART RepRoductive techniques seRies Infertility in Practice Fourth Edition A d A m H B A l e n Infertility in Practice REPRODUCTIVE MEDICINE AND ASSISTED REPRODUCTIVE TECHNIQUES SERIES David Gardner University of Melbourne, Australia Zeev Shoham Kaplan Hospital, Rehovot, Israel Kay Elder, Jacques Cohen Human Preimplantation Embryo Selection, ISBN: 9780415399739 Michael Tucker, Juergen Liebermann Vitrification in Assisted Reproduction, ISBN: 9780415408820 John D Aplin, Asgerally T Fazleabas, Stanley R Glasser, Linda C Giudice The Endometrium, Second Edition, ISBN: 9780415385831 Nick Macklon, Ian Greer, Eric Steegers Textbook of Periconceptional Medicine, ISBN: 9780415458924 Andrea Borini, Giovanni Coticchio Preservation of Human Oocytes, ISBN: 9780415476799 Steven R Bayer, Michael M Alper, Alan S Penzias The Boston IVF Handbook of Infertility, Third Edition, ISBN: 9781841848105 Ben Cohlen, Willem Ombelet Intra-Uterine Insemination: Evidence-Based Guidelines for Daily Practice, ISBN: 9781841849881 Adam H Balen Infertility in Practice, Fourth Edition, ISBN: 9781841848495 Infertility in Practice Fourth Edition AdAm H BAlen MB BS, MD, DS c , FRCOG Professor of Reproductive Medicine and Surgery, Leeds Teaching Hospitals, UK Boca Raton London New York CRC Press is an imprint of the Taylor & Francis Group, an informa business CRC Press Taylor & Francis Group 6000 Broken Sound Parkway NW, Suite 300 Boca Raton, FL 33487-2742 © 2014 by Taylor & Francis Group, LLC CRC Press is an imprint of Taylor & Francis Group, an Informa business No claim to original U.S Government works Version Date: 20130919 International Standard Book Number-13: 978-1-84184-850-1 (eBook - PDF) This book contains information obtained from authentic and highly regarded sources While all reasonable efforts have been made to publish reliable data and information, neither the author[s] nor the publisher can accept any legal responsibility or liability for any errors or omissions that may be made The publishers wish to make clear that any views or opinions expressed in this book by individual editors, authors or contributors are personal to them and not necessarily reflect the views/opinions of the publishers The information or guidance contained in this book is intended for use by medical, scientific or health-care professionals and is provided strictly as a supplement to the medical or other professional’s own judgement, their knowledge of the patient’s medical history, relevant manufacturer’s instructions and the appropriate best practice guidelines Because of the rapid advances in medical science, any information or advice on dosages, procedures or diagnoses should be independently verified The reader is strongly urged to consult the drug companies’ printed instructions, and their websites, before administering any of the drugs recommended in this book This book does not indicate whether a particular treatment is appropriate or suitable for a particular individual Ultimately it is the sole responsibility of the medical professional to make his or her own professional judgements, so as to advise and treat patients appropriately The authors and publishers have also attempted to trace the copyright holders of all material reproduced in this publication and apologize to copyright holders if permission to publish in this form has not been obtained If any copyright material has not been acknowledged please write and let us know so we may rectify in any future reprint Except as permitted under U.S Copyright Law, no part of this book may be reprinted, reproduced, transmitted, or utilized in any form by any electronic, mechanical, or other means, now known or hereafter invented, including photocopying, microfilming, and recording, or in any information storage or retrieval system, without written permission from the publishers For permission to photocopy or use material electronically from this work, please access www.copyright.com (http://www.copyright.com/) or contact the Copyright Clearance Center, Inc (CCC), 222 Rosewood Drive, Danvers, MA 01923, 978-750-8400 CCC is a not-for-profit organization that provides licenses and registration for a variety of users For organizations that have been granted a photocopy license by the CCC, a separate system of payment has been arranged Trademark Notice: Product or corporate names may be trademarks or registered trademarks, and are used only for identification and explanation without intent to infringe Visit the Taylor & Francis Web site at http://www.taylorandfrancis.com and the CRC Press Web site at http://www.crcpress.com Dedicated to Toby and Cara © 2011 Taylor & Francis Group, LLC Contents Foreword ix Preface .xi Section I Infertility – Background, Diagnosis and Counselling Infertility – Epidemiology, Diagnosis and Counselling Prevention of Infertility 13 Planning a Pregnancy 27 Obesity and Reproduction 49 Investigating Infertility 63 Counselling 135 Section II Management – Diagnosis and Treatment Anovulatory Infertility and Ovulation Induction 145 Polycystic Ovary Syndrome 201 Premature Ovarian Insufficiency (Failure) and Oocyte Donation 239 10 Endometriosis 251 11 Tubal Infertility and Fibroids 269 12 Male Factor Infertility 291 13 Unexplained Infertility 315 © 2011 Taylor & Francis Group, LLC vii viii Contents Section III Assisted Conception, Ethical Issues and Regulation 14 Assisted Conception 323 15 The Human Fertilisation and Embryology Authority and Regulation 365 16 Ethical Issues 375 17 Follow-Up of Children Born from Assisted Reproduction Techniques 387 Section IV Complications of Treatment and New Technologies 18 Complications of Ovarian Stimulation 395 19 Emerging Technologies 417 Section V Pregnancy 20 Miscarriage after Fertility Treatment 427 21 Recurrent Miscarriage 441 22 Ectopic Pregnancy 451 Section VI Treatment Failure 23 When to Stop Treatment and Other Options 459 Useful Addresses 465 Books for Further Reading 467 Appendix 469 © 2011 Taylor & Francis Group, LLC Foreword It gives me great pleasure to write the foreword for the Fourth Edition of Infertility in Practice, written by Professor Adam Balen With the current emphasis on sophisticated assisted reproductive techniques (ARTs), the critical contribution of clinical experience and expertise and common practical sense to diagnosis and clinical decision making is often overlooked This book presents a practical perspective and gives the clinician a clear picture of the aetiology of infertility The most common causes of infertility, such as polycystic ovary syndrome (PCOS), endometriosis, tubal damage, male factor and unexplained aetiology, have been described in detail, avoiding speculations that are not based on scientific knowledge Infertility treatment options are described in detail, and the book gives the reader a clear understanding of the current treatment practices I especially liked Chapter 14, Assisted Conception, which describes the present view on treating patients in some special situations For example, the indication of hydrosalpinges in ultrasound is a clear sign for their removal as the procedure improves implantation and pregnancy rates Furthermore, in moderate-to-severe endometriosis, in vitro fertilisation (IVF) is recommended if pregnancy is not anticipated within 12 months after surgery Similarly, in severe sperm dysfunction or after unsuccessful cycles of superovulation combined with intrauterine insemination (IUI), IVF should be offered, and in men with azoospermia it is reasonable to attempt 12 cycles of donor insemination in women younger than 35 years of age An interesting option is to test fertilisation after one IVF treatment before superovulation and IUI Some of the less commonly used – and also these days, obsolete – ART treatments are described briefly, but, understandably, the most frequently used procedures of IVF have received most space and different stimulation options have been described in detail Also, special situations, such as ovarian cysts, PCOS and patients with decreased ovarian reserve, have been clarified in separate chapters The results of different treatment options, and the impact of the number of attempts on pregnancy outcome, have been described Ethical issues are a very essential part of ART treatments, and questions such as experiments on human pre-embryos, cloning, stem cell research, fetal sex selection and reduction have been considered in many respects The book identifies potential ART-treatment-related complications and pregnancy problems, and it summarises the present data on the possible health consequences of the children born from ART treatments This fourth edition echoes the format of previous editions, but many of the tables and images have been updated All in all, the book gives an excellent insight into the leading causes of infertility, infertility treatments, pregnancy and health of the child I believe that the readers can easily obtain a comprehensive understanding of the recent developments in this particular field, and I am sure they would enjoy reading © 2011 Taylor & Francis Group, LLC ix 300 Infertility in Practice The development of ASABs in women could be due either to a deficient epithelial barrier in the genital tract, peritoneal cavity or gastrointestinal tract or to inadequate immunosuppressive substances in the seminal plasma Reassuringly, although perhaps surprisingly, there does not appear to be an increased rate of ASAB formation in women who have undergone IUI The rate of detection of ASABs in the serum, semen and cervical mucus of infertile couples ranges from 5% to 25%, compared with less than 2% in fertile couples A wide range of tests is used (see Chapter 5), and the cut-off levels of a significant concentration of antibodies are poorly defined Furthermore, the detection of ASABs in the serum does not necessarily equate with a significant problem in the genital tract, so the value of performing serum assays is uncertain ASABs may impair sperm motility Sperm-associated IgG activates complement and results in binding to polymorphonuclear leukocytes that then inactivate the sperm IgA is secreted from the endocervix and fallopian tubes and further affects sperm motility and, possibly, fertilisation There is a good correlation between the presence of cervical mucus ASABs and both sperm motility in cervical mucus and pregnancy rates Fertilisation rates also are reduced if more than 80% of sperm are bound with IgA ASABs, possibly by interfering with capacitation and the a crosome reaction There are numerous publications that deal with the effects of ASABs, but opinions still differ as to whether IgA or IgG antibodies are the more significant Furthermore, although some studies suggest that antibodies directed against the sperm head disrupt fertilisation directly, others consider that antibodies directed to the tail are of greater significance because they interfere with sperm movement Management The management of patients with ASABs is problematic Corticosteroids are used widely in men and suppress serum ASAB concentrations, but they appear to have less of an effect on sperm-bound ASABs Corticosteroid therapy has several side effects (e.g mood changes, which can be severe; gastritis; weight gain) and complications (e.g duodenal ulceration, hypertension, glucose intolerance, aseptic necrosis of the femoral neck) A suggested regimen is prednisolone 40 mg daily from day to day 10 of the partner’s menstrual cycle, reducing to 20 mg on day 11 or 12 and then stopping (some use or 10 mg/day for day 11 or 12) [17] It has been suggested that therapy should continue for at least months to have a beneficial effect on pregnancy rates, although some studies have found that steroids provide no benefit [18] It has been suggested that the men who gained most benefit from oral corticosteroids were those men who started with significantly higher concentrations of IgG (tail) antibodies and grade I motility [19] Since the advent of ICSI, the use of corticosteroid therapy has largely been abandoned At present, it is not possible to wash antibodies off sperm in vitro without damaging the sperm Pregnancy rates tend to be low with IUI when there are associated ASABs IVF offers a better chance of a pregnancy, although it is important not to use the female partner’s serum for incubation (as was often done in the past) if she has a significant concentration of ASABs There is conflicting evidence as to whether steroid therapy improves the outcome of IUI or IVF for men with ASABs If these therapies are required, in our opinion it is probably the assisted conception rather than the steroids that enhances fecundity © 2011 Taylor & Francis Group, LLC Male Factor Infertility 301 Obstructive Azoospermia No underlying cause can be found in more than one-half of patients with obstruction of the epididymis The cause is often infective in origin, particularly in developing countries, although less so in the West; infective causes include gonorrhoea, Chlamydia, filariasis, tuberculosis and bilharzia Congenital Bilateral Absence of the Vasa Deferentia In two-thirds of European men with congenital bilateral absence of the vasa deferentia (CBAVD), there are associated mutations of the genes that cause cystic fibrosis (CF) Pregnancies have been achieved using epididymal sperm, but the fertilisation rates are reduced Furthermore, the CF gene complex mutations will be present in one-half of the children born by these techniques, and we not yet know how many of the male offspring will have the same problems as their fathers Both partners should therefore undergo genetic screening before treatment, although at least two-thirds of men with isolated bilateral absence of the vas and point mutations of the CF gene complex not have symptoms of CF Sperm autoantibodies are often present when the vasa deferentia are absent Young’s Syndrome Young’s syndrome involves a combination of chronic respiratory problems and obstructive azoospermia, secondary to inspissated epididymal secretions The epididymes are often large and cystic, the vasa deferentia are normal and there are no ASABs There was an association between the development of this condition and the use of tooth powders containing mercury, which are no longer available Young’s syndrome overlaps both CF and Kartagener’s syndrome Kartagener’s Syndrome Kartagener’s syndrome, or immotile cilia syndrome, is an autosomal recessive condition in which male infertility caused by reduced sperm motility is associated with sinusitis, bronchiectasis and transposition of viscera (e.g dextrocardia) There is an ultrastructural defect in the dynein arms that creates ciliary movements by causing movement between adjacent microtubules Surgical Trauma and Vasectomy Surgical obstruction of the vas deferens may occur accidentally during childhood surgery for an inguinal hernia, during the repair of a hydrocele or deliberately during vasectomy The breach of the blood–testis barrier results in ASAB production only after puberty Surgical reconstruction of the vasa in a man who requests reversal of vasectomy is associated with a significant rate of ASABs, and the success of surgery declines with increasing time over years post-vasectomy [20] © 2011 Taylor & Francis Group, LLC 302 Infertility in Practice Microsurgical Reconstruction of the Vasa A vasovasostomy should only be undertaken by a skilled urologist using an operating microscope and 9–0/10–0 nylon sutures The anastomosis is traditionally performed in two layers, although this has been modified in some cases In a review of nearly 1500 vasectomy reversals, the patency rate was 97% and the pregnancy rate 76% in men within years of the vasectomy The figures were 76% and 30%, respectively, if the vasectomy had been performed more than 15 years previously [20] Even without the use of an operating microscope, patency has been achieved in up to 80% with pregnancy rates of 50% after 2–3 years Vasoepididymostomy is required if there is blockage in the epididymis, and it is most successful if the anastomosis, which can be end to end or end to side of a single epididymal tubule, is performed in the distal epididymis (Figures 12.2 through 12.4) Whenever any of these surgical procedures are performed, it is essential to have the facilities available to collect a sample of sperm for cryopreservation, either from the epididymis or directly from the testis Sperm stored in this way can be kept in reserve for future IVF/ICSI if the primary operation is unsuccessful Vas deferens Patent epididymal tubule Tail of epididymis Transected epididymis FIGURE 12.2 Microsurgical anastomosis: vasoepididymostomy End-to-end anastomosis of a single epididymal tubule The distal epididymis is transected, and the obstructed area excised if necessary After identifying a patent epididymal tubule, an anastomosis is performed to the vas © 2011 Taylor & Francis Group, LLC Male Factor Infertility FIGURE 12.3 End-to-side anastomosis FIGURE 12.4 Side-to-side anastomosis of epididymis and vas deferens © 2011 Taylor & Francis Group, LLC 303 304 Infertility in Practice If reconstructive surgery fails, it may be possible to retrieve sperm surgically from either the epididymis or the testis In simple cases, for example, after vasectomy, a percutaneous epididymal sperm aspiration (PESA) can be performed under local anaesthetic If this aspiration fails, a direct transcutaneous approach called testicular sperm extraction (TESE) can be attempted Alternatively, microsurgical epididymal sperm aspiration (MESA) may be performed (Figure 12.5) under general anaesthetic Spermatozoa thus obtained are cryopreserved They are usually of insufficient quantity or quality for either insemination or conventional IVF, but they may well when ICSI is performed (see Chapter 14) Idiopathic Male Factor Infertility If there is no obvious reason for sperm dysfunction, as is the case in perhaps 50% of patients, the choice lies between assisted conception (e.g superovulation/IUI or IVF ± micromanipulation techniques) or empirical treatments A huge number of empirical treatments have been tried, but none with any objectively demonstrated success For completeness, we list these therapies, before dismissing them: • hCG, hMG or anti-oestrogen (clomifene citrate, tamoxifen) therapies are of no value in normogonadotropic idiopathic male infertility; in some cases, sperm numbers may be increased but most are abnormal • Testosterone administration is similarly ineffective and might be contraceptive • Testolactone increases serum FSH concentrations by inhibiting the conversion of testosterone to oestradiol, but this process is of unproven value in male infertility • Bromocriptine has been used unsuccessfully; if serum prolactin levels are elevated, the consequence is usually impotence rather than infertility • The results of individual trials with kallikrein show no real benefit, although when pooled there might be a slight beneficial effect Kallikrein does not play a part in our clinical practice • The caffeine-derivative pentoxifylline enhances sperm function in vitro but neither oral pentoxifylline nor caffeine aids natural conception • Artificial vaginal insemination of an unprepared sample of the husband’s sperm (AIH) is pointless Paternal Ageing There is an increased risk of congenital genetic defects with older fathers, just as there is with older mothers (see Chapter 2) Such conditions include dominant disorders such as achondroplasia, myositis ossificans, Alpert’s syndrome, Marfan’s syndrome, Duchenne muscular dystrophy, haemophilia and the sex-linked recessive bilateral retinoblastoma It has been suggested that there is a link between male factor © 2011 Taylor & Francis Group, LLC 305 Male Factor Infertility (a) (b) (c) FIGURE 12.5 Microsurgical epididymal sperm aspiration (MESA) from (a) the proximal epididymis, (b) vasa efferentia and (c) rete testis © 2011 Taylor & Francis Group, LLC 306 Infertility in Practice infertility and accelerated testicular ageing, so that patients with infertility may have an increased risk of producing offspring with the above-mentioned conditions Coital Dysfunction and Psychosexual Problems Psychosexual Problems It is self-evident that if there are problems with sexual function, fertility will be impaired Furthermore, the desire for a child, which might be stronger in one partner, exacerbates psychosexual difficulties These problems require a sympathetic approach, with counselling by trained personnel Erectile Dysfunction Penile erection is under parasympathetic control (S2,3,4), and the rigidity of the corpora cavernosa requires testosterone, an intact arterial supply and venous closure The sympathetic nervous system initiates ejaculation (T10–L2), and closure of the internal sphincter of the bladder prevents retrograde ejaculation The varied causes of impotence and failure to ejaculate are listed below Approximately 80% of cases of erectile dysfunction have a cause, usually associated with reduced blood supply, and only 20% are psychogenic • Impotence: psychogenic, anxiety, depression, peripheral arterial disease, diabetes mellitus, hyperprolactinaemia, hypogonadism and antihypertensive and psychotropic drugs • Ejaculatory failure: psychogenic, hypogonadism, phenothiazines, α-blockers, aortic or abdominal surgery (e.g abdominal perineal (AP) resection), radial prostatectomy spinal cord injury, sympathetic nervous system injury, diabetes mellitus and multiple sclerosis Impotence/erectile dysfunction may be managed in primary care Men and their partners will benefit from counselling and the role of negative and positive psychological, behavioural and relationship influences on their sexual behaviour Treatment is initially with a phosphodiesterase type-5 inhibitor (e.g oral sildenafil, tadalafil or vardenafil) If oral medication has failed, the next step is either an intracavernosal injection or an intraurethral pellet of prostaglandin El (alprostadil) or papaverine This procedure must be performed with care and initially under medical supervision Vascular microsurgery is indicated if there is vascular disease and localised arterial lesions Inflatable penile prostheses also have been used with varying degrees of success It is important not to give testosterone to men with impotence caused by neuropathic lesions (e.g men with diabetes mellitus) as it increases libido, which cannot be satisfied, and worsens an already most distressing condition Many causes of ejaculatory failure can be treated using external vibratory massage, which can be performed by the patient or his partner placing a vibrator at the base of the penis and collecting semen for self-insemination If this approach fails, electroejaculation can be achieved using a rectal probe This probing has to be performed by © 2011 Taylor & Francis Group, LLC Male Factor Infertility 307 properly trained personnel because of the risk of autonomic dysreflexia and profound hypertension Electroejaculation has been used for many spinal cord–injured men Semen quality tends to decline with time after the injury, so the collected sperm often has to be used for IVF/ICSI rather than intravaginal insemination or IUI Sperm reservoirs have been used in some cases, and these reservoirs are surgically attached to the epididymis and sperm is withdrawn transcutaneously when the reservoir is full, but they frequently block and they have not gained popularity Recently, aspiration of sperm from the vas has achieved success Drug therapies include α-agonists, such as ephedrine hydrochloride (25 mg twice daily), although retrograde ejaculation is a common sequela Retrograde Ejaculation Retrograde ejaculation can occur after prostatectomy, bladder neck injury, sympathectomy or with diabetes or multiple sclerosis If the ejaculate is absent or of small volume (