Measuring success in IVF is a complex multidisciplinary task: time for a consensus?

The goal of an IVF cycle is the birth of at least one baby per intention to treat. However, IVF cannot confer competence on an embryo, but only can provide each couple with a safe treatment to meet a predetermined chance of success. This commentary highlights how clinical, financial and patient-centred perspectives should be included in the definition of success in IVF. The primary outcome, which is the cumulative live birth delivery rate per intention to treat, must always be complemented by analyses of risks, costs and time invested, as well as by measures of patient satisfaction. Finally, it is essential, whenever clinical conditions exist, to limit treatment discontinuation after failed attempts. Constant monitoring of the data is pivotal and must be adjusted for patient characteristics and compared with national and international registers. The authors aimed to review all these aspects and highlight the points that are still open for discussion. Is it time for a consensus?

Non-informative results and monosomies in PGD: the importance of a third round of re-hybridization.

The incidence of non-informative results after fluorescence in-situ hybridization (FISH) was analysed in preimplantation genetic diagnosis (PGD). FISH was performed on seven chromosomes (13, 16, 18, 21, 22, X, and Y) in two rounds of hybridization (one biopsied blastomere per day 3 embryo). A third round with telomeric probes was performed in order to analyse the chromosome(s) in question. A total of 702 embryos out of a total of 719 embryos from 95 cycles were analysed. The remaining 17 embryos were anucleated and/or had poor quality and could not be diagnosed. After FISH analysis, 52.7% of blastomeres were found to be abnormal, 27.1% euploid, and 20.2% had non-informative results. Abnormalities considered as non-informative included 'monosomy in question' (46.5%), 'trisomy in question' (40.2%), compound aneuploidy (8.5%), and 'no result' (4.9%) for a tested chromosome. Following re-hybridization with telomeric probes, euploidy was found in 42.4% of 'monosomies in question,' in 82.4% of 'trisomies in question,' in 16.7% of compound aneuploidies, and in 71.4% of 'no results' for a tested chromosome. Only 4.2% of non-informative results could not be rescued. This study clearly demonstrates the importance of re-hybridizing non-informative results and monosomies using a third round of hybridization with telomeric probes for chromosome(s) in question.

Blastocyst development after sperm selection at high magnification is associated with size and number of nuclear vacuoles.

Spermatozoa selection at high magnification before intracytoplasmic sperm injection seems to be positively associated with pregnancy rates after day 3 embryo transfers. The aim was to demonstrate an association between the presence of vacuoles in sperm nuclei and the competence of embryos to develop to day 5. Grading of spermatozoa at x 6000-x 12,500 magnification: grade I, no vacuoles; grade II, or=1 large vacuole; grade IV, large vacuoles with other abnormalities. The outcome of embryo development in a group of 25 patients after sibling oocyte injection with the four different grades of spermatozoa showed no significant difference in embryo quality up to day 3. However, the occurrence of blastocyst formation was 56.3 and 61.4% with grade I and II spermatozoa respectively, compared with 5.1% with grade III and 0% with grade IV respectively (P < 0.001). Spermatozoa selection at high magnification using Nomarski interference contrast is useful to identify more precisely the size and the number of nuclear vacuoles that greatly exert a negative effect on embryo development to the blastocyst stage. These observations confirm previous studies pointing to possible 'early and late paternal effects', both of which may have an impact on early embryonic development.

Leukemia inhibitory factor gene mutations in the population of infertile women are not restricted to nulligravid patients.

OBJECTIVE: Leukemia inhibitory factor (LIF) is one of the key cytokines in the embryo implantation regulation. We investigated the prevalence of the LIF gene mutations in the population of infertile women that consisted of nulligravid and secondary infertile patients. STUDY DESIGN: We designed a LIF gene mutation screening method that is based on the Temperature Gradient Gel Electrophoresis (TGGE). The population to screen consisted of 176 infertile women including group A of 147 nulligravid women and group B of 29 women with secondary infertility that had a history of either miscarriage or an ectopic pregnancy but no live births. The control population was comprised of 75 healthy fertile subjects. The groups of fertile controls and infertile patients were compared for statistically significant differences using the t-test. RESULTS: Six potentially functional LIF gene mutations, the G to A transitions at the position 3400 leading to the valin to methionin exchange at codon 64 (V64M) in the AB loop region of the LIF protein, were detected. All of the six positive women were infertile. Four of them were nulligravid and two of them had history of spontaneous conception followed by early miscarriage. No positive TGGE samples were identified in the control group, which means that the frequency of functionally relevant mutations of the LIF gene in infertile women is significantly enhanced in comparison with controls (P<0.05, t-test). CONCLUSION: The results suggest that the LIF gene mutations affect fertility. Even though they occur infrequently, their impact on molecular events during early phases of pregnancy should be further established.

[Vena cava filters in complicated venous thromboembolism. Ten years' experiences at Malmo University Hospital]. / Vena cava-filter vid komplicerad venös tromboembolisk sjukdom. Tio års erfarenheter från Universitetssjukhuset MAS.

All 74 patients treated with vena cava filter insertion during 1991-2000 at Malmö University Hospital were reviewed. Thirty-nine patients (53%) died during follow-up. Indications for permanent filter insertion (n = 63, age 25-89 years, 35 men) were contraindication for or side effects of anticoagulant treatment, or pulmonary embolism during anticoagulant treatment. Temporary vena cava filters (n = 11, age 19-85 years, three men) were inserted during surgery or thrombolysis. No complications occurred during temporary filter insertion. During 33 (1-120) months of follow-up of patients with permanent vena cava filters 37 patients (59%) died, thrombosis of the inferior vena cava occurred in 14 patients (22%), and recurrent pulmonary embolism in five patients (8%). Vena cava filter insertion should be considered as an alternative treatment in a selected group of patients with contraindications to or insufficient effect of anticoagulant treatment.

Pregnancy after ovarian superovulation by transdermal delivery of follicle-stimulating hormone.

Because of its size of 32 kDa and physicochemical properties, urinary FSH cannot permeate intact skin. We report the first pregnancy after laser microporation and transdermal delivery of FSH for ovarian superovulation as a substitute for SC or IM injections.

Methodological aspects of attempts to trans-differentiate adult stem cells into embryonic-like cells in vitro.

AIMS: The aim of this research was to set up an in vitro system to trans-differentiate haematopoietic stem cells (HSCs) into embryo-like stem cells in order to de-differentiate them. In this more naive state they should be cultivated more easily in order to augment them for consecutive differentiation and autologous transplantation for use in clinical practice. METHODS: Using the principle of the methodology of blastocyst injection, HSCs were co-cultivated with mouse embryonic stem cells (mES) with and without cell to cell contact. After co-cultivation HSCs were analyzed by flow-cytometry using haematopoietic markers (CD34, CD45, CD133) and embryonic stem cell markers (SSEA-4, Tra-1-60, Tra-1-81). RESULTS: No ES cell markers were detected on the former HSCs. A decrease in HSC marker intensity was the only finding. This implies that no de-differentiation took place. CONCLUSIONS: We hypothesize that the unnatural situation of a mixture of two cell types originating in different species may have led to this outcome. To achieve our goal of in vitro de-differentiation we need to use a purely human culture system without animal additives.

Extensive acute deep vein thrombosis of the iliocaval segment: midterm results of thrombolysis and stent placement.

PURPOSE: To evaluate patency and clinical outcome in patients treated with catheter-directed thrombolysis and stent placement for acute extensive thrombosis affecting the iliocaval segment. MATERIALS AND METHODS: During a 10-year period (1994-2005), 37 patients with 44 limbs (26 female, median age 31 years) with acute extensive venous thrombosis affecting the iliocaval segment were treated with catheter-directed thrombolysis. Angioplasty and stent placement was performed in 36 limbs (82%) for underlying stenosis or residual thrombosis. A prospectively registered database was analyzed in combination with a telephone interview about clinical symptoms. RESULTS: Technical success was achieved in all 44 limbs and clinical success in 42 of 44 (96%) limbs. Primary patency after a median imaging follow-up interval of 16 months was 34 of 44 (77%) limbs, assisted primary patency was 38 of 44 (86%) limbs, and secondary patency was 39 of 44 (89%) limbs. Thirty of 44 (68%) limbs were asymptomatic after a median clinical follow-up of 27 months, eight (18%) limbs were moderately improved, two (5%) limbs were unchanged, two (5%) limbs were moderately worse, and two (5%) limbs had no clinical follow-up. Complications occurred in six (16%) patients, three (8%) of which were major complications. No patient developed symptomatic pulmonary embolism. CONCLUSIONS: Catheter-directed thrombolysis and stent placement is a safe and effective treatment for acute iliocaval thrombosis. Clinical midterm results are encouraging. Thrombolyzed and stented segments remain patent in the vast majority of patients after 16 months. Primary and aggressive stent placement in the iliocaval vein segments can prevent rethrombosis and ensure patency.

Subintimal angioplasty of infrainguinal arterial occlusions for critical limb ischemia: long-term patency and clinical efficacy.

PURPOSE: To evaluate long-term patency and clinical efficacy of subintimal angioplasty (SAP) of occluded infrainguinal arteries 3 years post procedure. METHODS: One hundred eighty-one patients (92 men; median age 79 years) underwent attempted SAP in 193 limbs with occluded infrainguinal arteries during the period 1999 to 2001. Nearly half (83, 46%) of the patients had diabetes. Most (172, 95%) had critical ischemia (Fontaine classification>II). All patients surviving at least 3 years after the procedures were followed in January 2005 with questionnaires, clinical examinations, ankle-brachial index measurements, and duplex ultrasonography. All data were collected prospectively and analyzed retrospectively. RESULTS: The primary technical success in the entire cohort was 77% (148/193). Thirty-day mortality was 10% (19/181); 113 (62%) patients died before the 3-year follow-up. In the 68 (38%) survivors (71 limbs), patency at 49.2 months (IQR 40.8-57.6) was 40% (26/65 limbs imaged by duplex). The TASC classification did not affect technical or clinical outcomes. Forty-six (68%) of the survivors presented with clinical improvement (lower Fontaine classification at postoperative follow-up versus baseline). The limb salvage at >3 years was 86% in the 58 primarily successful SAPs and 38% in the 13 procedures that failed initially. CONCLUSION: SAP is a minimally invasive option for patients with critical limb ischemia. A primary technical success is essential for good clinical outcome and primary technical failure is more devastating than late occlusion. TASC classification and length of the SAP are of poor predictive value. More data are needed to confirm the efficacy of SAP.

Long-term results of stenting for chronic iliac artery occlusion.

PURPOSE: To evaluate the long-term results of stent placement for chronic occlusions of the iliac arteries. METHODS: Between October 1992 and December 1997, 73 patients (40 men; median age 64 years, range 42-89) with 76 occluded iliac arteries (33 common, 34 external, and 9 both vessels) were treated with percutaneous recanalization and stenting using a variety of self-expanding and balloon-expandable devices. Median occlusion length was 7 cm (range 1-14). Follow-up consisted of clinical assessment, ankle-brachial index measurement, and arteriography or duplex ultrasound when indicated. RESULTS: Anatomical success was achieved in 74 (97%) limbs. Seven (10%) patients experienced major complications: 2 distal embolizations, 2 arterial ruptures, 1 myocardial infarction, 1 groin hematoma requiring surgery, and 1 contrast-induced nephropathy. There was no 30-day mortality. Over a median follow-up of 27 months (range 1-75), there was 1 early occlusion (< or = 30 days) and 16 late recurrent lesions (11 occlusions and 5 stenoses) at a median 6.2 months (range 1.4-30). The recurrent lesions were treated with endovascular techniques in 8 limbs and surgery in 7 limbs (5 after failed endovascular procedures); 1 patient died before retreatment, and 1 patient refrained from further intervention. Primary and secondary patencies were 79% and 87% at 1 year and 69% and 81% at 3 years, respectively. CONCLUSIONS: Stenting of chronic iliac occlusions is a safe and durable alternative to surgical treatment.