Live birth following preimplantation genetic screening for trisomy 21. Should aneuploidy screening be offered to all older patients undergoing IVF?

A 42-year-old female patient with history of secondary infertility was referred to our assisted conception unit for in vitro fertilization (IVF). Before her referral, she had two cycles of IVF at another centre; the first was unsuccessful and, after conceiving at the second attempt, the pregnancy was terminated at 14 weeks' gestation following a positive nuchal translucency scan and a diagnosis of trisomy 21 (Down syndrome) by a chorionic villous biopsy performed in the first trimester. The screening tests for trisomy 21 were offered to the patient in view of her advanced age. Subsequent karyotyping revealed that both partners had a normal chromosomal complement. Following genetic counselling, the couple were offered IVF treatment along with preimplantation genetic screening for trisomy 21. Four of the five embryos were suitable for biopsy, and one blastomere from each embryo was analyzed using fluorescent in situ hybridization for chromosome 21. The analysis revealed that two embryos had trisomy 21, one had monosomy 21, and only one embryo was diploid for chromosome 21. The single diploid embryo was transferred to the uterus on day 3, and resulted in an uneventful pregnancy and delivery of a healthy live-born male.

Prolonged survival in culture of preantral follicles from polycystic ovaries.

CONTEXT: In polycystic ovary syndrome (PCOS), an increased proportion of follicles leave the primordial (resting) pool and initiate growth. However, there is little evidence for a reduced reproductive life span (early menopause) in women with PCOS, suggesting that the dynamics of follicle growth, and of follicle loss by atresia, is altered in PCOS. OBJECTIVE: The aim of this study was to investigate the possibility that loss of preantral follicles by atresia is reduced in PCOS, leading to prolonged follicle survival. DESIGN: We compared follicle growth in normal and polycystic ovaries using cultures of small ovarian biopsies. SETTING: Tissue samples were obtained at routine laparoscopy from 12 patients with anovulatory PCOS and 16 controls and processed in an ovarian physiology laboratory. MAIN OUTCOME MEASURES: We performed morphometric analysis of follicle population in tissue fixed at time of biopsy (d 0) or after 5, 10, or 15 d in culture. Analyses included assessment of follicle and oocyte diameter, number and proportion of primordial and growing follicles, and number and proportion of atretic follicles. RESULTS: In tissue fixed on d 0, the proportion of healthy growing follicles was, as expected, greater in ovaries from PCOS patients than in normal ovaries (64 vs. 28%; P = 0.0005), but there were no differences between PCOS and normal tissue during culture. The rate of atresia throughout the period of culture in follicles was, however, significantly lower in PCOS tissue (P < 0.0001). After culture, 80% of follicles in normal ovarian tissue were atretic compared with 53% in PCOS biopsies. CONCLUSION: Follicles from polycystic ovaries demonstrate a decreased rate of atresia in culture, suggesting a mechanism for maintaining a larger follicle pool throughout reproductive life.

Thrombocythemia and hemoperitoneum after transvaginal oocyte retrieval for in vitro fertilization.

OBJECTIVE: To present the first report of massive hemoperitoneum in a case of essential thrombocythemia after transvaginal oocyte retrieval for IVF and review the relevant literature related to the management of patients with this condition. DESIGN: Case report. SETTING: Assisted conception unit of a tertiary care university hospital in the United Kingdom. PATIENT(S): A 37-year-old woman with essential thrombocythemia who developed massive intra-abdominal bleeding after transvaginal oocyte retrieval for IVF. INTERVENTION(S): Emergency laparotomy and right salpingoophorectomy. RESULT(S): Resuscitation of the patient. MAIN OUTCOME MEASURE(S): Overall management of the patient is discussed. CONCLUSION(S): The management of patients with essential thrombocythemia at the childbearing period poses a difficult problem. Fertility may be reduced, and an adverse outcome of pregnancy due to thrombotic or bleeding complications is a matter of concern. A multidisciplinary approach with close and early cooperation with the hematologists before initiation of IVF therapy for patients with essential thrombocythemia is essential. Efforts should be made to reduce the platelet count and assess the platelet function before embarking on IVF, keeping in mind the double jeopardy from bleeding and thrombosis in these cases.

A review of complications following transvaginal oocyte retrieval for in-vitro fertilization.

Transvaginal ultrasound guided oocyte retrieval (TVOR) during in vitro fertilization (IVF) treatment was first described in 1985. By virtue of its simplicity and effectiveness, it has gained widespread popularity and has now become the gold standard for IVF therapy. Nevertheless, despite the advantages, the aspiration needle may injure the adjacent pelvic organs and structures leading to serious complications. The most common complications are haemorrhage, trauma and injury of pelvic structures, and pelvic infection. Other complications described include adnexal torsion, rupture of endometriotic cysts, anaesthetic, and even vertebral osteomyelitis. In the last two decades, several reports have described the complications associated with this technique, and tried to address the risk factors and safety issues. However there is wide variation in the way this common procedure is performed, with room for improvement through published guidelines. This article reviews the most common complications reported in literature, summarizes the recommendations made to minimize their occurrence, and raises some of the controversial issues related to the procedure especially that of pelvic infection.

Role of Insulin-like growth factors in initiation of follicle growth in normal and polycystic human ovaries.

CONTEXT: Polycystic ovary syndrome (PCOS), the commonest cause of anovulatory infertility, is characterized by disordered follicle development including increased activation and accelerated growth of preantral follicles. Data from experimental animals and preliminary results from studies of human ovarian tissue suggest that IGFs affect preantral follicle development. OBJECTIVE: Our objectives were to investigate the expression of the type-1 IGF receptor (IGFR-1) in the human ovary and to determine whether IGFs are involved in stimulating the transition of follicles from primordial to primary stage in normal and polycystic ovaries. DESIGN: We used archived ovarian tissue for protein expression studies and small cortical biopsies for follicle isolation and for tissue culture. SETTING: This was a laboratory-based study, using clinical tissue samples. PATIENTS: A total of 54 women, 33 with normal ovaries and 21 with polycystic ovaries, were classified by reference to menstrual cycle history and ultrasonography. MAIN OUTCOME MEASURES: We evaluated expression of IGFR-1 mRNA in isolated preantral follicles and of IGFR-1 protein in archived ovarian tissue samples from normal and polycystic ovaries and effects of exogenous IGF-1 on preantral follicle development and survival in cultured fragments of normal and polycystic ovaries. RESULTS: IGFR-1 mRNA and protein was expressed in preantral follicles at all stages of development and enhanced expression was noted in PCOS follicles during early preantral development. IGF-1 stimulated initiation of follicle growth in normal tissue but had little effect on preantral follicle growth in polycystic ovaries in which, characteristically, there was a higher proportion of follicles that had entered the growing phase even before culture. CONCLUSIONS: IGFs are plausible candidates in regulation of initiation of human follicle growth, and accelerated preantral follicle growth in PCOS may be due to increased activity of endogenous IGFs.

Infertile women with isolated polycystic ovaries are deficient in endometrial expression of osteopontin but not alphavbeta3 integrin during the implantation window.

OBJECTIVE: To characterize possible endometrial defects in infertile women with isolated PCO morphology. DESIGN: Prospective study. SETTING: An academic hospital with an IVF unit. PATIENT(S): Women with primary unexplained infertility and isolated PCO, fertile women, and women with infertility secondary to male factor. INTERVENTION(S): Thirty-one women (fertile and with male factor infertility) had endometrial sampling across the menstrual cycle. Nine fertile women and 10 infertile women with isolated PCO had sampling on day LH +7, adjusted for histologic dating. MAIN OUTCOME MEASURE(S): Expression of alphavbeta3 and its ligand, osteopontin, were determined using real-time quantitative polymerase chain reaction and immunohistochemistry. In vitro regulation of osteopontin was assessed using the Ishikawa cell line. RESULT(S): Cyclic variations revealed a fall in integrin alphavbeta3 mRNA during the secretory phase with concomitant up-regulation of osteopontin mRNA. Immunohistochemistry on day LH +7 demonstrated a significant reduction in expression of osteopontin in the isolated PCO group with no difference in expression of alphavbeta3. In vitro studies confirmed up-regulation of osteopontin by estrogen with no apparent effect of androgen. CONCLUSION(S): These results demonstrate an apparent reduction of osteopontin expression, important in cell-cell adhesion, during the window of implantation in infertile women with isolated PCO morphology.

A dedicated ectopic pregnancy team leads to an improvement in patients' management.

INTRODUCTION: The aim of the study is to determine whether a dedicated ectopic pregnancy team improves the management of haemodynamically stable patients with suspected ectopic pregnancy who do not require immediate life-saving surgery. METHODS: A non-randomized population based study involving 210 patients admitted with a suspected ectopic pregnancy over a 2-year period in a university teaching hospital in the UK, was carried out to compare the management of those women before and after the introduction of the ectopic pregnancy team. RESULTS: Following the introduction of an ectopic pregnancy team, there were fewer laparotomies performed, fewer negative diagnostic laparoscopies, a reduced overall surgical intervention rate, and a reduced duration of hospital stay. Although, it was difficult to quantify the extent of improvement of training, yet there were fewer operations performed out-of-hours, more continuity of care, more learning opportunities and acquisition of laparoscopic skills of junior staff. CONCLUSIONS: The introduction of an ectopic pregnancy team led to an improvement in the management of patients with suspected ectopic pregnancies. Efforts aiming at setting up such a specialized team and its implementation in day-to-day clinical practice should be considered in hospitals where the mainstay of treatment remains laparotomy.

Use of inferior epigastric artery embolization to arrest bleeding at operative laparoscopy.

OBJECTIVE: To describe an innovative approach of embolization of the inferior epigastric artery after vascular trauma due to lateral trocar insertion at operative laparoscopy. DESIGN: Case report. SETTING: Operating theater and interventional radiology suite of a university hospital. PATIENT(S): A 26-year-old woman with polycystic ovaries refractory to clomiphene citrate undergoing laparoscopic ovarian drilling. INTERVENTION(S): Percutaneous selective left external iliac and left inferior epigastric angiography followed by embolization with platinum microcoils and polyvinyl alcohol. MAIN OUTCOME MEASURE(S): Satisfactory hemostasis following traumatic injury to the inferior epigastric artery. RESULT(S): Hemostasis was achieved using a novel interventive radiologic approach of embolization of the inferior epigastric artery after conventional surgical techniques had failed. CONCLUSION(S): Arterial embolization is a novel additional measure in the armamentarium of the laparoscopic surgeon faced with intractable bleeding from the inferior epigastric vessels.

Successful spontaneous pregnancy following surgical removal of a post uterine artery embolized necrotic fibroid capsule: a case report.

Uterine artery embolization has been shown to be an effective treatment in controlling symptomatic uterine fibroids. Reports suggest that significant complications associated with the procedure are rare. However, data pertaining to preservation of fertility after embolization are scarce, and some authors do not advocate this procedure for women considering future pregnancy. We present a case of a post-embolization uterine cavity abnormality which was repaired surgically, followed by successful pregnancy outcome.

Analysis of epitopes on endometrial epithelium by scanning immunoelectron microscopy.

Scanning immunoelectron microscopy was applied to human endometrial epithelium for the first time to simultaneously determine epitope localisation and cellular architecture. The method was established using HMFG1, an antibody to a glycoform of the MUC1 mucin. This was chosen because of the potential importance of MUC1 in connection with endometrial receptivity. Biopsies of mid-secretory phase endometrium were labelled using HMFG1 and silver-enhanced, gold-conjugated secondary antibody was then visualised by back-scattered electron imaging. The method provided a highly specific localisation of the HMFG1 epitope to the ciliated and "ciliogenic" cells of the endometrial surface. In contrast, no reactivity was evident on the microvillous cells and endometrial pinopodes. The potential to integrate the study of the molecular and ultrastructural changes that occur in the endometrium by using scanning immunoelectron microscopy offers a powerful means of expanding our understanding of the adaptation of the endometrium in preparation for embryo implantation.

Resultados de tratamento com fertilizaçåo in vitro e transferência de embriöes em pacientes com endometriose / results of in vitro fertilization for the treatment of patients with endometriosis

Os resultados da literatura sugerem que o resultado do tratamento com FIV-TE para pacientes com endometriose depende do estadiamento da doença, sendo que pacientes com endometriose severa têm uma elevada taxa de insucesso. A presença de abortamento é supostamente mais prevalente em mulheres em tratmento para endometriose. Cento e quarenta pacientes com endometriose submeteram-se a 182 ciclos de FIV-TE utilizando a GnRH. Pacientes com endometriose como única patologia foram alocadas em um grupo, e os resultados foram comparados com outros três grupos de pacientes submetidas ao mesmo tratamento, durante o mesmo período. O gupo 1 era composto de casais com fator masculino (45 ciclos);grupo 2, casais com ESCA (196 ciclos), e grupo 3, casais com fator tubário como única causa (1.139 ciclos). A idade média das pacientes, o número médio de ampolas de HMG utilizads, os níveis séricos de E2 no dia do ECG, o número de dias de HMG, o número médio de oócitos aspirados e a taxa de aspiraçäo näo foram significativamente diferentes. A taxa de fertilizaçäo foi significativamente inferior no grupo 1, sendo que nenhuma diferença foi observada entre osdemais três grupos. O número médio de embriöes normalmente fertilizados näo foi significativamente diferente. O número de embriöes transferidos por ciclo e a taxa de implantaçäo foi semelhante nos quatro grupos. A taxa de gravidez por TE foide 39 por cento no grupo 1;48 por cento no grupo 2;45 por cento no grupo 3 e 40 por cento no Grupo 4. A taxa de abortamento foi de zero para o grupo 1; 3,9 por cento para o grupo 2; 3,9 por cento para o grupo 3 e, diferente do exposto em todos os artigos prévios, nenhuma das pacientes grávidas e com endometriose apresentou abortamento. O grupo de endometriose foi dividido de acordo com a classificaçäo do AFS-r e analisado separadamente. Nenhuma diferença foi encontrada nos resultados entre as pacientes com estádio I-II e III-IV. Nossos resultados sugerem que a utilizaçäo de GnRH para supressäo hipofisária melhora os resultados de FIV-TE em pacientes com endometriose. A presença de endometriose e seu grau de severidade näo alteraram significativamente os resultados de FIV-TE, além disso näo encontramos evidências de elevaçäo nas taxas de abortamento espontâneo