Vered H. Eisenberg

Subfertility in the era of assisted reproduction: changes and consequences

OBJECTIVEnTo review the major changes that have occurred during the last decade of assisted reproduction technology (ART) practice, looking at the various conditions that cause subfertility.nnnDESIGNnA short review describing the progress that has been made during the last decade of ART practice, analyzing the various conditions that cause subfertility, is presented. The efficacy of ART as a treatment of these conditions is discussed.nnnCONCLUSIONSnAssisted reproductive technology currently is used for a wide range of indications and has become an acceptable tool in the treatment of subfertile couples. Yet, there is an ongoing debate regarding the effectiveness of ART versus conventional treatment for the various conditions that cause subfertility. The effectiveness of IVF in terms of pregnancy rate (PR) was demonstrated only for patients with severe bilateral tubal disease and male subfertility. For couples with other causes of infertility the differences in PRs do not reach statistical significance, and the efficacy of IVF has not been demonstrated clearly to date. Moreover, much of the discussion about management of subfertility has centered on costs of ART and the cost-benefit of ART versus conventional therapy for subfertility. It has been shown that, in women with unexplained infertility, menotropin treatment is as successful, less expensive, and carries a smaller risk than the surgical approach used in ART. However, the exact role of ART in the management of polycystic ovarian syndrome, immunological infertility, and endometriosis still is to be determined. Yet, as embryo implantation after ART still is considerably lower than that of fertile couples who conceive naturally, we expect that the next major thrust improving the effectiveness of ART will occur after future elucidation of factors influencing embryonic implantation.

Reproductive Outcome Is Favorable After Laparoscopic Resection of Bladder Endometriosis

STUDY OBJECTIVEnTo assess the reproductive outcome (spontaneous and assisted conception rates) in women who underwent laparoscopic resection of bladder endometriosis.nnnDESIGNnThis was a retrospective, observational study analyzing prospectively recorded data (Canadian Task Force classification II-2).nnnSETTINGnA tertiary referral center.nnnPATIENTSnOver a 9-year period, we identified 69 consecutive women with symptomatic pelvic endometriosis who underwent laparoscopic resection of bladder endometriosis at our center.nnnINTERVENTIONSnGroup A patients (nxa0=xa021) had full-thickness endometriotic invasion of the bladder and underwent laparoscopic partial cystectomy. Group B (nxa0=xa048) patients had partial endometriotic bladder penetration and underwent partial-thickness excision of the detrusor muscle. Most patients (over 70%) had additional, nonbladder endometriotic lesions, which were also removed during surgery.nnnMEASUREMENTS AND MAIN RESULTSnFertility outcomes were analyzed in patients who wished to conceive (nxa0=xa042), and improvements in symptoms were assessed for all patients. The minimum follow-up after surgery was 36xa0months. Of the 42 patients who wished to conceive, 35 patients (83.3%) conceived: 16 patients spontaneously and 18 patients after IVF treatment. No difference was observed in fertility outcome between group A (partial cystectomy) and group B (partial-thickness excision of the detrusor muscle). For all patients, long-term follow-up revealed that 80% of the patients (55 patients) had no urinary/endometrial symptoms after surgery.nnnCONCLUSIONnPregnancy rates after laparoscopic surgery for bladder endometriosis by either partial cystectomy or deep excision of the detrusor muscle are favorable, both for spontaneous pregnancy and conception after IVF treatment. Additionally, urinary symptoms were improved for the majority of patients. Based on our findings, it seems warranted to offer laparoscopic surgical management to symptomatic infertile patients diagnosed with bladder endometriosis, even after IVF failure.

Fertility outcome of laparoscopic treatment in patients with severe endometriosis and repeated in vitro fertilization failures

OBJECTIVEnTo evaluate fertility outcomes in infertile women with severe endometriosis (The revised American Fertility Society classification [AFS] 3-4) and repeated IVF failures, who underwent surgery due to exacerbation of endometriosis-related symptoms.nnnDESIGNnRetrospective cohort study.nnnSETTINGnUniversity hospital.nnnPATIENT(S)nAll women who failed IVF treatment before surgery and who underwent laparoscopic surgery for severe endometriosis betweenxa0January 2006 and Decemberxa02014.nnnINTERVENTION(S)nAll patients were operated by highly skilled surgeons specializing in laparoscopic surgery for advanced endometriosis. Only patients with evidence of endometriosis in the pathology specimens were included in this study.nnnMAIN OUTCOME MEASURE(S)nDelivery rate after surgery.nnnRESULT(S)nSeventy-eight women were included in the present study. All women were diagnosed with severe endometriosis during surgery (AFS 3-4) and all women had experienced failed IVF treatments before surgery. All women were symptomatic before their surgery. After surgical treatment 33 women (42.3%) delivered. Three women (9%) conceived spontaneously and all other women conceived after IVF treatment. Women who delivered were younger (32.5 [±4.1] years vs. 35.5 [±3.8] years), were less often diagnosed with diminished ovarian reserve before surgery (6% vs. 28.8%), and were more often diagnosed with normal uterine anatomy (by preoperative transvaginal ultrasound and during operation). In addition, performing salpingectomy during surgery was associated with a trend of improvement in delivery rates after surgery (70% in women who delivered vs. 51% in women who failed to deliver).nnnCONCLUSION(S)nSymptomatic women with severe endometriosis and repeated IVF implantation failures may benefit from extensive laparoscopic surgery when performed by an experienced multidisciplinary surgical team to improve IVF outcome.

The moral aspects of prenatal diagnosis

The incidence of significant birth defects or genetic disorders in pregnancy is approximately 3%. Some will be found to have a congenital or genetic defect during childhood or early adulthood. The demands of modern society are for a healthy perfect baby. Recent technological advances have enabled the development of techniques aimed at early diagnosis of the abnormal fetus, at a point where parents who wish to do so may terminate the pregnancy. Some of these techniques render the woman and fetus at risk of harm, whereas in others, efficacy has not yet been established. The implementation of these techniques raises several ethical questions which will be discussed in this article. We will also give a concise scientific background to the available techniques.

Epidemiology of endometriosis: a large population‐based database study from a healthcare provider with 2 million members

Endometriosis constitutes a significant burden on the quality of life of women, their families and healthcare systems. The objective of this study is to describe the real‐world epidemiology of endometriosis in an unselected low‐risk population in Israel.

The ethical, legal and religious aspects of preembryo research

Recent advances in the field of reproduction have made it possible to obtain preembryos and to use them in many research applications. These include research into improving methods of IVF treatment, contraceptive research, preimplantation diagnosis, gene therapy, the study of malignant disease, and others. The benefits, academic and scientific, are enormous. Apart from these benefits are many moral, legal, religious and ethical problems and reservations. Potential sources from which the preembryos may originate may also lead to controversy. Pressure groups in various societies seek to hasten governments into legislation or other means of control. We conducted a Medline search of all pertinent literature since 1980, and the findings are reviewed following. Regulated use of preembryo research is ethically acceptable by most groups in society. Suggestions for regulation are provided.

Genetic engineering: moral aspects and control of practice.

ConclusionsPresent-day scientific advances have made it possible to use somatic cell gene therapy for the treatment of serious human genetic disease. Gene therapy is enormously important for curing some diseases, otherwise untreatable. The technical ability to perform germline gene alteration is also under way. Society must determine its attitude toward germline alteration and toward intervention for the purpose of genetic enhancement. Eugenic genetics is purely theoretical at present and is likely to remain so for a long time. Articles in the press, sometimes influenced by specific pressure groups, generate public fear that is in most cases unfounded, due to the lack of feasibility of performing the claims voiced in them. Still, society must be concerned about the possibility that gene therapy will be misused in the future. Gene therapy should only be used in ways that maintain human dignity. The best insurance against misuse is a public well informed and not unnecessarily frightened. With proper safeguards imposed by society, gene therapy can be ethically used.

PREEMBRYO RESEARCH : MEDICAL ASPECTS AND ETHICAL CONSIDERATIONS

Recent advances in the field of reproduction have made it possible to obtain preembryos and to use them in many research applications. These include research into improving methods of IVF treatment, contraceptive research, preimplantation diagnosis, gene therapy, the study of malignant disease, and others. The benefits, academic and scientific, are enormous, but many moral and ethical issues and reservations exist. Potential sources from which the preembryos may originate may also lead to controversy. Pressure groups in various societies seek to hasten governments into legislation or other means of control. We conducted a MEDLINE search of all pertinent literature since 1980, and these findings have been reviewed.

The duties of ethical committees applied to human reproduction

ConclusionsModern ethics in todays pluralistic society has changed the face of medical practice. Commissions appointed by institutions, governments, and international bodies serve to alleviate the medical profession from making ethical decisions and to protect human subjects from any harm. The deliberations of these committees are usually followed by guidelines of operation, which in many cases have become abiding law. In order for committees to be of full advantage, they must convene promptly as issues arise, so as not to delay medical advances from being implemented.

Infertility treatments during pregnancy and the risk of autism spectrum disorder in the offspring

&NA; We aimed to examine the effects of infertility treatments on the risk of Autism Spectrum Disorder (ASD). Data were from a representative national registry on 110,093 male live births in Israel (born: 1999–2008; and ASD: 975, 0.9%). Infertility treatments included In Vitro Fertilization (IVF), and five hormone treatments. Relative risk (RR) was estimated with multivariable logistic models. Results showed that IVF treatment compared with spontaneous conception was not statistically significantly associated with the risk of ASD. Only progesterone hormone treatment was associated with a statistically significant (p < .05) increased risk of ASD (RR = 1.51, 95% CI 1.22, 1.86) compared to the group with no progesterone treatment. In conclusion, progesterone exposure during the critical period of fetal life elevated the risk of ASD, possibly reflecting epigenetic modification. HighlightsTested the association of infertility treatment with Autism Spectrum Disorder (ASD) in childrenUsed a representative national registry study designProgesterone hormone treatment significantly increased the risk of ASD.Possibly observed epigenetic modification by progesterone