Prediction of live birth in frozen-thawed single blastocyst transfer cycles by pre-freeze and post-thaw morphology.

STUDY QUESTION: What pre-freeze and post-thaw morphological parameters can be used to predict live birth outcomes after frozen-thawed blastocyst transfer cycles? SUMMARY ANSWER: Pre-freeze blastocoele expansion and trophectoderm (TE) grade and post-thaw degree of re-expansion are the most significant predictors of live birth in frozen-thawed blastocyst transfer cycles. WHAT IS KNOWN ALREADY: Currently, blastocoele re-expansion after thawing is used to indicate blastocyst cryosurvival and reproductive potential. The predictive roles of other pre-freeze and post-thaw morphological parameters are neglected. STUDY DESIGN, SIZE, DURATION: This was a retrospective study of all the patients who received a frozen-thawed single blastocyst transfer (n = 1089) at our clinic between March 2008 and October 2011. PARTICIPANTS/MATERIALS, SETTING, METHODS: Pre-freeze morphological parameters analyzed for all blastocysts included grade of blastocoele expansion, inner cell mass and TE. A group of blastocysts (n = 243) were also graded for post-thaw parameters: degree of blastocoele re-expansion, viability and cell contour. Univariate and multivariate generalized estimating equations (GEEs) models were used to identify the confounders that statistically significantly affected live birth outcomes and to investigate the independent effect of significant pre-freeze and post-thaw morphological parameters. Stepwise logistic regression analysis was used to select the best independent morphological predictors of live birth. Pearson correlations and linear regression analyses were performed to determine the relationship between morphological parameters and possible covariates. MAIN RESULTS AND THE ROLE OF CHANCE: Multivariate GEE models estimated that the odds of live birth increased by ∼36% for each grade of expansion (P = 0.0061) and decreased by 29% for blastocysts with grade B TE compared with grade A TE (P = 0.0099). Furthermore, the odds of live birth increased by ∼39% (P = 0.0042) for each 10% increase in degree of re-expansion. Blastocoele expansion and TE grade were selected as the most significant pre-freeze morphological predictors of live birth and degree of re-expansion was selected as the best post-thaw parameter for prediction of live birth. LIMITATIONS, REASONS FOR CAUTION: Blastocysts with poorer grades of morphology were not cryopreserved or transferred, limiting the ability to generalize our findings for grades of morphology not included in this study. WIDER IMPLICATIONS OF THE FINDINGS: Blastocysts with higher pre-freeze grades of expansion and TE, irrespective of day of cryopreservation, should be given priority when thawing. Subsequently, re-expanding blastocysts, assessed within 2-4 h, with >60% viability should be transferred. STUDY FUNDING/COMPETING INTEREST(S): No external funding was obtained for this study. There was no competing interest. TRIAL REGISTRATION NUMBER: not applicable.

Non-invasive metabolomic profiling of Day 2 and 5 embryo culture medium: a prospective randomized trial.

BACKGROUND: Near infrared (NIR) spectroscopy is a technology proposed to facilitate non-invasive screening for the most optimal human embryo for uterine transfer. It has been proposed that the NIR spectral profile of an embryo's spent culture medium can be used to generate a viability score that correlates to implantation potential. As the initial proof of principle studies were all retrospective, our aim was to investigate whether NIR spectroscopy on spent embryo culture medium in an on-site, prospective setting could improve the ongoing single embryo transfer (SET) pregnancy rate after Day 2 and 5 transfers. METHODS: We conducted a single-centre, double-blinded, randomized controlled trial in which the NIR group was compared with a control group. The primary outcome was the clinical pregnancy rate after 6-7 weeks of gestation per randomized patient. In the control group embryo selection was based only on traditional morphological evaluation while in the treatment group NIR spectroscopy was added to the morphological evaluation. RESULTS: The study was terminated early as the analysis of the Data Safety Monitoring Board showed a very low conditional power of superiority for the primary outcome. Of the 752 patients calculated to be included in the study, 164 and 163 patients were randomized into the NIR and control groups, respectively. No significant difference in the ongoing pregnancy rate per randomized patient was found between the NIR and the control group, 34.8 versus 35.6%, (P= 0.97). The proportional difference between the study groups mean was -0.8% (95% confidence interval -11.4 to 10.2). CONCLUSIONS: This study shows that adding NIR spectroscopy, in its present form, to embryo morphology does not improve the chance of a viable pregnancy when performing SET. The NIR technology appears to need further development before it can be used as an objective marker of embryo viability. CLINICAL TRIALS IDENTIFIER: ISRCTN23817363.

Trophectoderm morphology: an important parameter for predicting live birth after single blastocyst transfer.

BACKGROUND: In order to select the best blastocyst for transfer, in humans, three morphological parameters have routinely been used, i.e. degree of blastocoele expansion and appearance of both the trophectoderm (TE) and the inner cell mass (ICM). Although it has been shown that blastocysts with highest scores for all three parameters achieve highest implantation rates, their independent ability to predict pregnancy outcome remains unclear. METHOD: This study is a retrospective analysis of 1117 fresh day 5 single blastocyst transfers and their live birth outcome related to each morphological parameter. RESULTS: All three parameters had a significant effect on live birth however, once adjusted for known significant confounders, it was shown that TE was the only statistically significant independent predictor of live birth outcome. CONCLUSIONS: This study has shown, for the first time, the predictive strength of TE grade over ICM for selecting the best blastocyst for embryo replacement. It may be that, even though ICM is important, a strong TE layer is essential at this stage of embryo development, allowing successful hatching and implantation.

A randomized controlled study comparing pain experience between a newly designed needle with a thin tip and a standard needle for oocyte aspiration.

UNLABELLED: BACKGROUND; Ultrasound-guided transvaginal oocyte retrieval is often performed under local anaesthesia on an outpatient basis. The objective of this study was to compare the overall pain experience of a newly designed reduced needle (RN) compared with a thicker standard needle (SN). METHODS: A prospective, randomized, multi-centre study was performed at four different clinics from June to December 2009. The oocyte aspiration was performed under local anaesthesia, either with a needle with a reduced diameter (0.9 mm) for the last 50 mm from the tip (RN) or with a SN (1.4 mm). A total of 257 patients were randomized (RN: n = 129; SN: n = 128). The primary endpoint was the overall pain experience self-assessed and registered by the patient on a visual analogue scale (VAS 0 mm = no pain to 100 mm = unbearable pain) immediately after the oocyte retrieval. Secondary end-points such as vaginal bleeding and several embryological parameters were also registered. RESULTS: The overall pain during the oocyte retrieval procedure was significantly lower in the RN group than in the SN group (mean 21.0 mm, SD 17.5 mm and median 19.0 mm versus mean 26.0 mm, SD 19.9 mm and median 24.0 mm; P = 0.040, difference between groups mean-5.0 mm, 95% CI: 9.7 to-0.4). This was also true when adjusting for baseline characteristics such as number of follicles, number of previous oocyte pick-up, body mass index and age, by a multiple linear regression analysis. Significantly more patients (40 of 126) had less than expected vaginal bleeding in the RN group when compared with the SN group (24 of 124; 32 versus 19%; P = 0.03 and 95% CI 1.7-23.0%). No differences were found between the two needles with regard to additional i.v. analgesia, aspiration time, oocyte recovery, fertilization, cleavage rate, number of good quality embryos, number of embryos for freezing and pregnancy rate. CONCLUSIONS: Oocyte aspiration performed with the newly designed thinner-tipped needle resulted in significantly less overall pain and less vaginal bleeding, without prolonging the retrieval procedure or influence the oocyte recovery rate, when compared with a SN. Clinicaltrials.gov: NCT00924885.

Individualizing FSH dose for assisted reproduction using a novel algorithm: the CONSORT study.

The CONSORT dosing algorithm individualizes recombinant human FSH (r-hFSH) doses for assisted reproduction technologies, assigning 37.5 IU increments according to patient characteristics: basal FSH, body mass index, age and antral follicle count. A prospective, uncontrolled, international, 18-centre, pilot study of normo-ovulatory women aged 18-34 years inclusive undergoing a long agonist treatment protocol was performed. Follitropin alfa filled-by-mass (GONAL-f®) dose was assigned by the algorithm and was intended to be altered only for risk of ovarian hyperstimulation syndrome (OHSS). Primary end-point was number of oocytes retrieved. Dose groups containing ≥5 patients were analysed: 75 IU (n = 48), 112.5 IU in = 45), 150 IU (n = 34), 187.5 IU (n = 24), 225 IU (n = 10). Cancellations due to inadequate response were higher than expected in the 75 IU group (12/48). Overall, a median of 9.0 oocytes were retrieved (8.5, 8.0, 10.0, 12.0 and 8.0 in the 75, 112.5, 150, 187.5 and 225 IU groups respectively). Clinical pregnancy rates/cycle started were 31.3, 31.1, 35.3, 50.0 and 20.0%, respectively (overall, 34.2%). Two patients had severe OHSS. Use of the CONSORT algorithm achieved an adequate oocyte yield and good pregnancy rates in this preliminary study. Adjustment of the algorithm could reduce cancellation rates.

Obstetric outcomes after transfer of vitrified blastocysts.

BACKGROUND: It has been claimed that the risks to the child resulting from vitrification as compared with the slow-freezing technique, may be higher owing to the high concentrations of potentially toxic cryoprotectants. We therefore retrospectively compared the obstetric and neonatal outcomes in a cohort of children born after transfer of vitrified blastocysts, fresh blastocysts and slow-frozen early cleavage stage embryos. METHODS: All children born after transfer of vitrified blastocysts (n = 106), fresh blastocysts (n = 207) and slow-frozen early cleavage stage embryos (n = 206) during the period January 2006 to May 2008 at Fertility Center Scandinavia were included. Data on obstetric and neonatal outcomes were obtained from medical records from the antenatal and delivery clinics. RESULTS: For singletons, there were no significant differences between the groups in gestational age, mortality or birth defects. After adjustment for parity and BMI, birthweight was significantly higher in singletons born after transfer of vitrified blastocysts as compared with after transfer of fresh blastocysts (median 3560 versus 3510 g, P = 0.0311). More singletons born after transfer of fresh blastocysts were small for gestational age compared with singletons born after transfer of vitrified blastocysts (12.1 versus 3.0%, P = 0.0085). A higher rate of major post-partum haemorrhage was observed in the vitrified blastocyst group as compared with the other two groups (25.0 versus 6.0 and 7.5%). CONCLUSIONS: No adverse neonatal outcomes were observed in children born after transfer of vitrified, as compared with fresh blastocysts or after transfer of slow-frozen early cleavage stage embryos.

Re-analysis of 166 embryos not transferred after PGS with advanced reproductive maternal age as indication.

BACKGROUND: In a randomized controlled study aiming to test the effectiveness of preimplantation genetic screening (PGS) in women of advanced maternal age, embryos diagnosed as chromosomally abnormal and those with no diagnosis were fixed for reanalysis. The aim of this study was to determine how well the chromosomal constitution of one biopsied blastomere reflects the status of the entire embryo. METHODS: One hundred and seventy-three embryos diagnosed as chromosomally abnormal, 22 with no PGS result and four degenerated embryos originally diagnosed as normal were fixed and reanalysed by fluorescence in situ hybridization. RESULTS: In total, 199 embryos were fixed, of which 166 were successfully reanalysed. One hundred and sixty embryos were found to be chromosomally abnormal; 48 of the reanalysed embryos with an initial diagnosis (149) had at least one cell with exactly the same chromosomal constitution shown in the first PGS analysis (34.2%). The reanalysis confirmed the initial overall chromosomally abnormal status of the embryo in 95.9% of the cases. Of all chromosomally abnormal embryos, 4.1% were diagnosed as false positive. The risk for false negative rate was at least 4.1%. CONCLUSIONS: PGS seems to be a good method for selecting against chromosomally abnormal embryos but not for determining an embryo's exact chromosomal constitution.

Individualizing FSH dose for assisted reproduction using a novel algorithm: the CONSORT study.

The CONSORT dosing algorithm individualizes recombinant human FSH (r-hFSH) doses for assisted reproduction technologies, assigning 37.5 IU increments according to patient characteristics: basal FSH, body mass index, age and antral follicle count. A prospective, uncontrolled, international, 18-centre, pilot study of normo-ovulatory women aged 18-34 years inclusive undergoing a long agonist treatment protocol was performed. Follitropin alpha filled-by-mass (GONAL-f) dose was assigned by the algorithm and was intended to be altered only for risk of ovarian hyperstimulation syndrome (OHSS). Primary end-point was number of oocytes retrieved. Dose groups containing >or=5 patients were analysed: 75 IU (n = 48), 112.5 IU (n = 45), 150 IU (n = 34), 187.5 IU (n = 24), 225 IU (n = 10). Cancellations due to inadequate response were higher than expected in the 75 IU group (12/48). Overall, a median of 9.0 oocytes were retrieved (8.5, 8.0, 10.0, 12.0 and 8.0 in the 75, 112.5, 150, 187.5 and 225 IU groups respectively). Clinical pregnancy rates/cycle started were 31.3, 31.1, 35.3, 50.0 and 20.0%, respectively (overall, 34.2%). Two patients had severe OHSS. Use of the CONSORT algorithm achieved an adequate oocyte yield and good pregnancy rates in this preliminary study. Adjustment of the algorithm could reduce cancellation rates.

Preimplantation genetic screening in women of advanced maternal age caused a decrease in clinical pregnancy rate: a randomized controlled trial.

BACKGROUND: Advanced maternal age (AMA) is an important parameter that negatively influences the clinical pregnancy rate in IVF, in particular owing to the increased embryo aneuploidy rate. It has thus been suggested that only transferring euploid embryos in this patient group would improve the pregnancy rate. The purpose of this study was to test whether employing preimplantation genetic screening (PGS) in AMA patients would increase the clinical pregnancy rate. METHODS: We conducted a two-center, randomized controlled trial (RCT) to analyze the outcome of embryo transfers in AMA patients (>or=38 years of age) after PGS using FISH analysis for chromosomes X, Y, 13, 16, 18, 21 and 22. The PGS group was compared with a control group. The primary outcome measure was clinical pregnancy rate after 6-7 weeks of gestation per randomized patient. RESULTS: The study was terminated early as an interim analysis showed a very low conditional power of superiority for the primary outcome. Of the 320 patients calculated to be included in the study, 56 and 53 patients were randomized into the PGS and control groups, respectively. The clinical pregnancy rate in the PGS group was 8.9% (95% CI, 2.9-19.6%) compared with 24.5% (95% CI, 13.8-38.3%) in the control group, giving a difference of 15.6% (95% CI, 1.8-29.4%, P = 0.039). CONCLUSIONS: Although the study was terminated early, this RCT study provides evidence against the use of PGS for AMA patients when performing IVF. TRIAL REGISTRATION NUMBER: ISRCTN38014610.

The application of quality systems in ART programs.

A quality control (QC) system is needed in ART units to assure reproducibility of all methods and competence in all duties performed by the personnel. The necessity of a quality control system becomes even clearer when considering the possible risks of ART. It is therefore essential to have a system to assure that everybody knows exactly how everything should be done. Furthermore, a QC system should bring about improvements such as making activities and procedures clearer to the staff and making the working methods more flexible. QC was initially created for the industry, and has later been applied to other types of activities such as management of organizations, services like health care including different types of clinical testing laboratories. To maintain a high standard in our IVF laboratory, and to assure reproducibility of the methods used we decided to apply for accreditation according to the European Norm (EN) 45001 and requirements for the competence of testing laboratories ISO/IEC Guide 25. A process was started where all routines and methods within the laboratory were documented and finally the QC system was described in a quality manual. Application for accreditation was submitted to the Swedish board for accreditation and conformity assessment (SWEDAC). Our ART laboratory finally became accredited according to the EN 45001 and requirements for the competence of testing laboratories ISO/IEC Guide 25. Introducing and fully implementing a quality control system in our laboratory has standardized the methods and the way that the embryologists perform their work in the laboratory. It has also optimized the environment in which the patient's gametes and embryos are handled.

Patients' experience of transvaginal follicle aspiration under local anesthesia.

The development of vaginal ultrasound transducers has facilitated ovum pick-up (OPU) by providing higher precision and less trauma than are found with laparoscopy and other ultrasound-assisted techniques. In order to evaluate the patients' acceptance, 65 patients were asked to answer a questionnaire about their experience with the procedure. The punctures were executed with specially designed needles introduced through a needle guide attached to a vaginal transducer with a frequency of 7 MHz (Brüel & Kjaer, Denmark). The anesthesia consisted of a light premedication and a paracervical block. If needed, a small dose of sedative was given intravenously intraoperatively. The patients classified their pain experience within the day of the puncture on a four-grade scale. Their statements were compared to the physician's opinion of the discomfort caused. Oocytes were retrieved from all patients. Fifty-one patients answered the questionnaire, of whom five found the OPU painful. In two cases the physician underestimated the patients' pain experience. The mean time required for the procedure was 16 min/OPU. We conclude that transvaginal ultrasound-guided OPU is well accepted by most patients under local anesthesia and that it is a rapid and accurate procedure.

Structural and functional evidence for the denervation of human myometrium during pregnancy.

The neuronal influence of the contractility of the term-pregnant human uterus was studied by pharmacologic and histochemical methods. By the use of adrenergic and cholinergic antagonists or tetrodotoxin it was demonstrated that the contractile response of superfused myometrial strips from the term-pregnant uterus to electrofield stimulation was not influenced by any neuronal factor. Using an indirect immunofluorescence technique with an antiserum to the glial and Schwann cell specific S-100 protein, a marked paucity of nerve fibers was demonstrated in myometrial strips from the term-pregnant uterus as compared with the nonpregnant uterus. It is concluded that the described decrease of nerve fibers within the myometrium of the pregnant uterus may be of importance for the myometrial activity during pregnancy and parturition.

Recruitment of an ovulatory follicle in the human following follicle-ectomy and luteectomy.

The study was undertaken to explore the time required for the selection and ovulation of a dominant follicle after interference with the normal menstrual cycle of fertile women. At routine laparotomy (sterilization) a leading follicle or a fresh corpus luteum was excised, and the day of the next ovulation was estimated by monitoring of serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), progesterone, and 17 beta-estradiol and by registration of the growth of the follicles through ultrasonic scanning. The results are in accordance with earlier observations in the rhesus monkey demonstrating that the recruitment and selection of an ovulation-competent follicle takes 12 to 14 days in the primate. Since this time is close to the length of the normal follicular phase and approximately the same after follicle-ectomy and luteectomy, the results suggest an importance of local factors in regulating follicle recruitment.

Factors of importance for the establishment of a successful program of intracytoplasmic sperm injection treatment for male infertility.

OBJECTIVE: To establish an intracytoplasmic sperm injection treatment program for couples with male infertility and to determine those factors important for success. DESIGN: A retrospective analysis of 171 consecutive cycles of intracytoplasmic sperm injection concerning 145 infertile couples. SETTING: Infertility clinic in a private hospital associated with a university hospital. PATIENTS: Couples with infertility in the male partner whose sperm parameters were unacceptable for conventional IVF or in whom fertilization by conventional IVF failed repeatedly. INTERVENTIONS: One hundred seventy-one transvaginal oocyte retrievals were completed after superovulation with GnRH agonist and gonadotropins. MAIN OUTCOME MEASURES: The parameters evaluated included fertilization, cleavage, implantation, pregnancy, and spontaneous abortion in relation to patient indications and improved procedures. RESULTS: After intracytoplasmic sperm injection, normal fertilization occurred in 45% of the oocytes (n = 1,499). Of 171 treatment cycles, 93% of the couples had fertilization and 86% had ET. Thirty-six pregnancies were achieved. During the period studied, the mean fertilization rate increased from 21.3% during the first 17 weeks to 67.8% during the last 13 weeks, and the pregnancy rate (PR) per started cycle increased from 12.8% to 31.3%. CONCLUSIONS: Technical factors critical for achieving high rates of fertilization and pregnancy were the use of standardized intracytoplasmic sperm injection pipettes, the immobilization of sperm before injection, and the aspiration of a minimal amount of ooplasm before reinjection with the sperm. Intracytoplasmic sperm injection appears to be superior to other micromanipulation methods for alleviating male infertility.

Collection of human oocytes by the use of sonography.

A technique for ultrasonically guided percutaneous oocyte aspiration was developed utilizing standard real-time, linear-array ultrasound equipment. Forty-four patients attending our in vitro fertilization and embryo transfer (IVF-ET) program were included in this study. In 38 patients, follicular puncture was performed under general anesthesia and in 6 cases performed under local anesthesia. Fifty-two follicles with a mean diameter greater than or equal to 18 mm were punctured, and 40 mature oocytes were recovered corresponding to a success rate of 77% per follicle. Six of the punctured follicles were considered cystic when the aspirated granulosa cells were examined microscopically and, if these were excluded, the corrected recovery rate was 87% per follicle. In two patients, ovulation had occurred at the time for oocyte collection. In one of these patients, a mature oocyte was, however, recovered from the pouch of Douglas by the use of sonography. On the basis of these results, ultrasonically guided puncture of follicles for collection of human oocytes in our IVF-ET program seems suitable for use in all cases where laparoscopy is presently used and, moreover, in cases with severe adhesions, where laparoscopy may fail.

Adjuvant growth hormone treatment during in vitro fertilization: a randomized, placebo-controlled study.

OBJECTIVES: To explore the effect of recombinant, human GH on follicular development and oocyte retrieval after gonadotropin stimulation with the addition of GH or placebo to a standard IVF treatment regimen. Further, to investigate whether GH is a more effective adjuvant if the standard treatment regimen is preceded by GH injections. DESIGN: A randomized, double-blind, parallel, placebo-controlled study. SETTING: The IVF unit at university hospital. PATIENTS: Forty normally ovulating women, age 25 to 38 years, with infertility because of tubal factors and being classified as "poor responders" with at least two previously performed and failed IVF attempts. INTERVENTIONS: Human, recombinant GH (Genotropin, Kabi Pharmacia, Uppsala, Sweden) or placebo (0.1 IU/kg body weight per day) was given SC as pretreatment during down regulation with GnRH and during stimulation with hMG according to the randomized protocol. MAIN OUTCOME MEASURES: Number of oocytes retrieved after stimulation, total amount of gonadotropin used, time required for stimulation, number of follicles developing, rate of fertilization, and cleavage in vitro. Further, the quality of embryos, development of the endometrium, rate of clinical pregnancy, and serum and follicular fluid (FF) concentrations of insulin-like growth factor I (IGF-I), insulin-like growth factor binding protein-1 (IGFBP-1), and IGFBP-3 were estimated. RESULTS: The number of oocytes retrieved did not differ significantly between the groups, nor did the amount of hMG required for stimulation. The fertilization rate increased in patients who had received GH. Growth hormone caused a significant increase in serum and FF levels of IGF-I. An increase in serum IGFBP-3 could also be recorded in patients who had received GH. CONCLUSION: Although certain beneficial effects were noted in GH-treated patients, the overall results did not support GH as a clinically useful adjuvant treatment.

Platelet-derived growth factor is detected in human blastocyst culture medium but not in human follicular fluid--a preliminary report.

The content of PDGF in human blastocyst culture medium (n = 8), serum (n = 12), and FF (n = 17) from natural IVF cycles was determined by an RIA specific for PDGF B-chain. The blastocysts were cultured under serum-free conditions throughout development. The findings show that PDGF B-chain is released into the culture medium of human blastocysts and that serum is positive, whereas FF is negative for PDGF.

Endometrial sonographic and histologic findings in women with and without hormonal replacement therapy suffering from postmenopausal bleeding.

OBJECTIVES: To evaluate, in women with postmenopausal bleeding, the effect of hormonal replacement (HRT) therapy on the endometrial thickness as measured by transvaginal sonography in relation to endometrial histology. METHODS: 1110 women with sequential/progestin treatment (E + P) (n = 202), with Estriol treatment (n = 149) or without HRT (n = 759) and postmenopausal bleeding were examined by transvaginal sonography (TVS) prior to curettage, with special reference to the relation of endometrial thickness to its histopathology. RESULTS: The distribution of endometrial pathology was different in those women with E + P and Estriol compared with those without HRT. Endometrial pathology was found most frequently in women with an endometrium exceeding 8 mm in thickness. Furthermore, the incidence was found to increase with increasing endometrial thickness in all treatment groups. Atrophy was found significantly more often in women without HRT. Hormonal effects on the endometrium were found significantly more often in women with E + P and Estriol. Endometrial hyperplasia was found most commonly in women with Estriol in the thickness group 5 8 mm (P < 0.001) as compared to those with HRT and without HRT. Endometrial cancer occurs most in women without HRT, in those women with an endometrium exceeding 8 mm in thickness as compared both to the E + P (P < 0.001) group and to the Estriol (P < 0.001) group. Endometrial cancer did not occur in any woman (with E + P, Estriol or without HRT) with an endometrial thickness of < or = 4 mm. CONCLUSIONS: TVS is of value for excluding endometrial pathology in women with HRT and postmenopausal bleeding. The distribution of endometrial findings and histopathological diagnosis in women with abnormal postmenopausal bleeding was different in women with E + P than in women without HRT. Furthermore, the cut-off for excluding endometrial abnormalities is the same in both groups i.e. < or = 4 mm.

Microfertilization techniques--the Swedish experience.

Intracytoplasmic sperm injection (ICSI) has been studied in this animal research programme since 1990. In 1993, the technique was first applied clinically and up to the present time (September 1994), a total of 456 couples have been studied in 538 cycles. The principal indication for the use of ICSI has been severe male sub-fertility as judged by a semen analysis. In addition, men with high titres of antisperm antibodies, blockage of the vas deferens and neurological disorders such as spinal cord lesions have been included in the programme. Men with genetic disorders such as cystic fibrosis and acrosome-deficient spermatozoa have also been treated successfully. The overall fertilization rate using ICSI was 59%, which is similar to the conventional in vitro fertilization (IVF) programme in Göteborg, however, the pregnancy rate per embryo transfer (29%) and the ongoing pregnancy rate per transfer (22%) were slightly lower. The total number of pregnancies was 144 with 111 of the pregnancies either ongoing or already delivered. To date, 36 healthy children have been born following 29 deliveries and no major malformations have been diagnosed. Being the first programme in Scandinavia to perform ICSI, this unit has experienced long waiting lists which indicates that severe male sub-fertility will be one of the major groups for treatment with assisted reproductive technologies in the future.

Relationship between electrical and mechanical activity of the isolated term-pregnant human myometrium.

In order to study the relationship between electrical and mechanical activity of isolated human myometrium in late pregnancy three different techniques were employed: the sucrose gap model, stiff pressure electrodes and flexible suction electrodes. A high degree of concordance was found between the various methods with regard to the pattern of electrical activity. However, the suction electrode technique seemed advantageous from a practical point of view due to its simplicity and high reproducibility. In the human myometrium each contraction was typically adjoined by a single spike potential, although trains of spikes were occasionally observed during the initial phase of the contraction. This contrasted to the bursts of spikes accompanying both the rising phase and the plateau phase of contractions in the myometrial specimens from the pregnant and estrous rat. This indicates a fundamental difference in electro-mechanical coupling mechanisms in the human myometrium when compared to the most widely used animal model for electrophysiological studies.