Women with homozygous AT deficiency type II heparin-binding site (HBS) are at high risk of pregnancy loss and pregnancy complications.

Data regarding outcome and therapy of pregnancies in patients with homozygous antithrombin (AT) deficiency are very rare. We conducted a retrospective, descriptive investigation with emphasis on the obstetric history of eight women with homozygous AT deficiency heparin-binding site (HBS), who had at least one pregnancy. The aim of the study was to get a better insight into the outcome and identify suitable management procedures of pregnancy in this rare disease. All patients suffered from homozygous AT deficiency caused by the mutation c.391C>T p.Leu131Phe in the AT gene (SERPINC1). The women reported in total 23 pregnancies; one pregnancy was excluded because of induced abortion. We found that only seven out of the 22 analyzed pregnancies ended with a live infant, all of them were born preterm. Among the 15 negative outcomes, seven were early pregnancy losses and eight were intrauterine fetal deaths. We found no clear association between treatment protocols and outcome. Eight pregnancies were not treated at all; all of them ended with pregnancy loss. We conclude that homozygous AT deficiency HBS, a form of severe thrombophilia, is associated with high risk of pregnancy loss and preterm delivery. Rigorous anticoagulation and/or replacement of AT during pregnancy may improve the outcome.

Application of a ready-to-use calcium ionophore increases rates of fertilization and pregnancy in severe male factor infertility.

OBJECTIVE: To analyze whether a ready-to-use calcium ionophore improves outcomes, from fertilization to live birth, in patients with severe male factor infertility. DESIGN: Artificial oocyte activation offered to applicable patients over a 20-month period. SETTING: Specialized in vitro fertilization (IVF) centers in Austria and Germany. PATIENT(S): Twenty-nine azoospermic and 37 cryptozoospermic men. INTERVENTION(S): Mature oocytes treated with a ready-to-use Ca(2+)-ionophore (GM508 Cult-Active) immediately after intracytoplasmic sperm injection (ICSI). MAIN OUTCOME MEASURE(S): Rates of fertilization, implantation, clinical pregnancy, and live birth. RESULT(S): Patients had had 88 previous cycles without artificial activation that resulted in a fertilization rate of 34.7%, 79 transfers (89.8%), and 5 pregnancies, which all spontaneously aborted except one. After artificial oocyte activation, the fertilization rate was 56.9%. In terms of fertilization rate, both azoospermic (64.4%) and cryptozoospermic (48.4%) men statistically significantly benefited from use of the ionophore. In 73 transfer cycles, positive ß-human chorionic gonadotropin levels were observed in 34 cases (46.6%) and 29 cycles (39.7%) that ended with a clinical pregnancy. The corresponding implantation rate was 33.3%. Four spontaneous abortions occurred (11.8%), and 32 healthy children were born. CONCLUSION(S): This is the first prospective multicenter study on artificial oocyte activation in severe male factor infertility. Present data indicate that a ready-to-use calcium ionophore can yield high fertilization and pregnancy rates for this particular subgroup. In addition to fertilization failure after ICSI, severe male factor infertility is an additional area for application of artificial oocyte activation.

Successful pregnancy in vitrified/warmed blastocyst intrafallopian transfer.

OBJECTIVE: To analyze whether the use of blastocyst intrafallopian transfer is a feasible option in a case of repeated difficult ET. DESIGN: Case report. SETTING: Public hospital. PATIENT(S): Forty-year old nulliparous patient. INTERVENTION(S): Transfer of two vitrified/warmed blastocysts into the right tube by means of laparoscopy. MAIN OUTCOME MEASURE(S): Successful ET, clinical pregnancy. RESULT(S): Successful ET procedure resulting in positive ß-hCG and clinical pregnancy. CONCLUSION(S): In cases of repeated difficult ETs (regardless of whether the patient shows cervical adhesions or any type of genital malformations), blastocyst intrafallopian transfer can be a successful alternative approach.

Ectopic pregnancies with unusual location and an angular pregnancy: Report of eight cases.

OBJECTIVE: The increased use of assisted reproduction techniques has been accompanied by an increase in ectopic pregnancies with unusual location being associated with significant maternal morbidity and mortality. This article reports on seven cases of ectopic pregnancies with unusual location and an angular pregnancy. Diagnostic and therapeutic strategies are discussed and a brief review of literature is presented. STUDY DESIGN: Case series of seven cases with ectopic pregnancy in unusual location, following assisted reproductive technique or conceived spontaneously (cesarean scar pregnancy and early abdominal pregnancy in mesoappendix) and an angular pregnancy, having presented at our hospital during the last eight years. Retrospective analyses. RESULTS: Interstitial pregnancy, cornual pregnancy, cesarean scar pregnancy, early abdominal pregnancy in omentum majus, heterotopic (cervical) pregnancy, early abdominal pregnancy in mesoappendix, angular pregnancy. All patients were surgically treated. CONCLUSION: Diagnosis of ectopic pregnancy with unusual location may be difficult, and differentiation of intact intrauterine or extrauterine pregnancy with adequate consideration of the area of uterine ostium of the fallopian tube may be delicate. Moreover, varying treatment strategies and high rates of complications aggravate the situation.

A new way of setting rFSH deposit: a case of severe injection error in IVF/ICSI cycle ending with live birth.

WE PRESENT A CASE WITH A SEVERE INJECTION ERROR: a 25- year old woman with secondary infertility caused by a male factor was enrolled in our IVF/ICSI-ET program. Stimulation was performed in a long- protocol and ovarian stimulation, using rFSH follitropin beta, starting on the third day of the menstrual cycle. The rFSH dose per day was 900 IU-0 IU-0 IU-0 IU. Due to normal ovarian response and follicle growth, stimulation was continued and there was no detriment in oocyte quality and no symptoms of OHSS. Following blastocyte transfer cesarean section was unpreventable at 37+5 weeks of gestation due to an impacted transverse lie. Different stimulation protocols are needed for appropriate treatment of various patients provided that the administration of treatment was done correctly. In the case of injection errors, continuing stimulation protocol seems to be achievable in certain cases considering hormone levels and the process of follicle growth.

Pharmacological stimulation of sperm motility in frozen and thawed testicular sperm using the dimethylxanthine theophylline.

OBJECTIVE: To evaluate whether the use of theophylline improves sperm motility and treatment outcome in frozen-thawed testicular sperm extraction (TESE). DESIGN: Artificial sperm activation was offered to azoospermic patients between January and October 2010 in two different centers (identical lab conditions). SETTING: IVF units of public hospitals. PATIENT(S): Sixty-five patients participated and gave informed consent. INTERVENTION(S): Sibling oocytes were split into a study (intracytoplasmic sperm injection [ICSI] with thawed testicular sperm treated with theophylline) and a control group (ICSI with thawed untreated sperm). MAIN OUTCOME MEASURE(S): Sperm motility, time for sperm selection, rates of fertilization, implantation, clinical pregnancy, and live birth. RESULT(S): All patients but one (98.5%) showed a significant improvement in testicular sperm motility when theophylline was used. In addition, sperm selection took significantly less time in the study as compared with in the untreated control group. Corresponding rates of fertilization (79.9% vs. 63.3%) and blastulation (63.9% vs. 46.8%) were significantly increased. Significantly more patients achieved clinical pregnancy if embryos/blastocysts derived from oocytes that had been injected with pharmacologically stimulated testicular spermatozoa were transferred (53.9% vs. 23.8%). This also holds true for the implantation rate. CONCLUSION(S): Theophylline turned out to be a reliable tool in stimulating testicular spermatozoa after thawing. Its immediate effect allows for faster and more accurate selection of viable sperm, which in turn improved fertilization and pregnancy outcome in this prospective study.

Age-related distribution of basal serum AMH level in women of reproductive age and a presumably healthy cohort.

In this study, day 1 to 4 serum anti-Müllerian hormone (AMH) level was analyzed in 2,741 patients attending our department for reproductive medicine or reproductive surgery, including a subgroup of 1,105 women who attended an assisted reproductive technology program because of a male factor as a presumably healthy subgroup. Day 1 to 4 serum AMH levels showed an age-dependent distribution and there is a wide range of AMH in each year of age analyzed, showing that even young women are at a risk of reduced ovarian reserve.

Assisting in vitro fertilization by manipulating cumulus-oocyte-complexes either mechanically or enzymatically does not prevent IVF failure.

OBJECTIVE: This prospective study was set up in order to analyze whether additional treatment (cutting off supernumerous cumulus cells; adding hyaluronidase) of the cumulus-oocyte-complex (COC) would help to improve treatment outcome. MATERIAL AND METHODS: COCs from 50 patients were prospectively subdivided into a control group A (no manipulation of COC) and two study groups. In group B, surplus cumulus cells were cut off using syringes, and in the second study group COCs were incubated with a 1:11 dilution of hyaluronidase (final concentration 7 IU/l). Main outcome measures were fertilization rate, embryo development, as well as rates of implantation, pregnancy, and live birth. RESULTS: Fertilization was higher in group C as compared to the untreated control group A (p<0.05). However, complete fertilization failure could not be avoided by any of the modified IVF approaches. Compaction on day 4 and blastocyst quality on day 5 were significantly improved in group C as compared to group B (but not to group A). Rates of implantation, pregnancy, and live birth were not affected by any of the methods. CONCLUSION: ICSI seems to be the only choice for avoiding the vast majority of fertilization failures after IVF.

Automatic user-independent zona pellucida imaging at the oocyte stage allows for the prediction of preimplantation development.

OBJECTIVE: To analyze whether a change in three-dimensional structure of the zona pellucida could indicate suboptimal gamete quality. DESIGN: Prospective study. SETTING: Women's general hospital. PATIENT(S): A total of 72 patients who gave informed consent. INTERVENTION(S): The birefringence of all oocytes was prospectively analyzed with an automatic user-independent polarization microscopy imaging system. MAIN OUTCOME MEASURE(S): Birefringence of the inner zona layer, preimplantation development, implantation, and pregnancy. RESULT(S): In approximately one third of all gametes (244/712), the system's automatic detection of the inner zona layer did not succeed. This phenomenon was a negative predictor of compaction (P<0.01), blastulation (P<0.001), and pregnancy (P<0.001). In cases of successful zona imaging, the score based on the birefringence of the inner zona layer was a strong predictor of blastocyst formation but not of embryo quality or pregnancy (P>0.05). Interestingly, antagonist protocol resulted in lower zona scores as compared with the long protocol (P<0.05). CONCLUSION(S): Combining the information from both undetected and detected oocytes, zona imaging was a helpful tool in oocyte selection. This knowledge might further help to reduce both the time in culture and the number of concepti considered for transfer.

[Is there an influence of IVF law on our medical treatment]. / Gesetzlicher Stellenwert und juristische Aspekte der Reproduktionsmedizin in Osterreich.

After first successful attempts of IVF treatment medical action was for the better part faced with a legislative vacuum. It took more than ten years until appropriate legal provisions for treatment in reproductive medicine could be established in Austria, thus eliminating numerous legal uncertainties. Compared to other countries patients and physicians can be satisfied with both public support by social security legislation (IVF Support Fund Act, 2000) and the regulations of the Reproductive Medicine Act (FMedG, 1992). An international comparison shows that legal provisions in Austria have avoided excessively liberal interpretation as well as the risk of excessively tight interpretation. Nevertheless, daily practice reveals serious flaws in these laws, which have been amended in 2004. One the one hand the Reproductive Medicine Act constitutes a severe infringement of the equal rights principle in certain situations, while other passages may result in a hastier use of invasive treatment methods than originally intended.

Anti muellerian hormone serum levels in women with endometriosis: a case-control study.

OBJECTIVE: To compare the anti muellerian hormone (AMH) serum levels in women with and without endometriosis. DESIGN: A case-control study SETTING: Women's General Hospital, Linz, Austria. PATIENT(S): Our study included a total of 909 patients undergoing in vitro fertilisation/intracytoplasmic sperm injection (IVF/ICSI) treatment or consulting our specific endometriosis unit. After proofing the exclusion criteria, 153 of these patients with endometriosis (study group) were matched with 306 patients undergoing IVF/ICSI treatment because of a male factor (control group). INTERVENTIONS: None. MAIN OUTCOME MEASURES: AMH serum level. RESULTS: Mean AMH serum level was significantly lower in the study than in the control group (2.75 + or - 2.0 ng/ml vs. 3.46 + or - 2.30 ng/ml, p < 0.001). In women with mild endometriosis (rAFS I-II), the mean AMH level was almost equal to the control group (3.28 + or - 1.93 ng/ml vs. 3.44 + or - 2.06 ng/ml; p = 0.61). A significant difference in mean AMH serum level was found between women with severe endometriosis (rAFS III-IV) and the control group (2.38 + or - 1.83 ng/ml vs. 3.58 + or - 2.46 ng/ml; p < 0.0001). CONCLUSION: Lower AMH serum levels and an association with the severity were found in women with endometriosis. Physicians have to be aware of this fact. Because of the expected lower response on a controlled ovarian hyperstimulation (COH), AMH serum level should be measured to optimise the dose of gonadotropin treatment previous to a COH, especially in women with severe endometriosis.

Cryopreserved blastocysts have a lower implantation but an equal live birth rate as compared to fresh blastocysts of the same quality - a case-control study.

The purpose of this case-control study was to compare implantation, pregnancy, and live birth rate of cryopreserved embryos with that of fresh embryos. A total of 1,488 assisted reproductive technology (ART) trials including 188 cryopreserved embryo replacement trials were reviewed. After proofing the exclusion criteria, 112 patients undergoing a cryopreserved embryo replacement (study group) were matched with 112 patients undergoing a fresh embryo transfer (control group). Matching was done for age of patients, number, and quality of embryos (Day 5 embryos). Data concerning maternal characteristics, survival rate of warming procedure, implantation, pregnancy, ongoing pregnancy, and live birth rates were collected. A lower implantation rate was found for cryopreserved embryo replacement compared to transferring fresh embryos. Live birth rate was found to be equal in both groups.

Risk in twin pregnancies after the use of assisted reproductive techniques.

OBJECTIVE: To analyze whether there is an increased perinatal risk for twin pregnancies after in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI). STUDY DESIGN: The medical files of 216 twin pregnancies (group 1) conceived through IVF/ICSI and 377 spontaneously conceived twin pregnancies (group 2) were assessed retrospectively. Data on gestational age at delivery, mode of delivery, birth weight, neonatal intensive care unit admission, duration of hospitalization, perinatal mortality and malformations were recorded. Statistical analysis was made by the chi2 test. Differences of the means of parametric data were analyzed using the Mann-Whitney test. RESULTS: The frequency of cesarean section was higher in group 1. Mean gestational age, frequency of preterm birth, birth weight, and frequency of low birth weight and very low birth weight were similar in both groups. The frequency of small-for-gestational-age (SGA) infants was significantly higher in group 1. Perinatal outcome, rate of malformations and neonatal mortality rate were similar in the 2 groups. CONCLUSION: We found an increased risk of SGA infants in IVF/ICSI twin pregnancies as compared to spontaneously conceived twin pregnancies.

The role of three-dimensional volume measurement in diagnosing endometrial cancer in patients with postmenopausal bleeding.

OBJECTIVE: To evaluate the role of three-dimensional transvaginal ultrasound in diagnosing endometrial cancer in patients with history of postmenopausal bleeding and compare its effectiveness with two-dimensional ultrasound. METHODS: Transvaginal ultrasound examinations, diagnostic hysteroscopy with subsequent curettage, and/or hysterectomy were performed in 213 consecutive patients with a history of postmenopausal bleeding. The results of the ultrasonographic examinations were compared with the diagnoses on the basis of histologic examination. In addition to an explorative data analysis, receiver operating characteristic curves were shown and areas under curves were calculated. Minimal endometrial volume (2.7 ml) and minimal endometrial thickness (7 mm) of endometrial carcinoma were defined as optimal cutoff values. RESULTS: In 42 patients, endometrial carcinoma was diagnosed. The mean endometrial volume of patients with endometrial cancer, measured by three-dimensional ultrasound, was 11.78 ml. The sensitivity of the endometrial volume at the optimal cutoff (2.7 ml) was 100.00%, the specificity was 69.00%, the positive predictive value was 44.20%, and the negative predictive value was 100.00%. On two-dimensional ultrasound, the mean endometrial thickness of patients with endometrial cancer was 16.6 mm. The sensitivity endometrial thickness measurements at the optimal cutoff (7 mm) was 100.00%, the specificity was 43.3%, the positive predictive value was 30.2%, and the negative predictive value was 100.00%. The area under curve of volume measured by three-dimensional ultrasound was 0.89 (95% CI 0.85-0.93). The area under curve of endometrial thickness was 0.85 (95% CI 0.80-0.91). The comparison of the area under curve of receiver operating curves between endometrial volume and endometrial thickness revealed a significant difference (p=0.023). CONCLUSION: Volume measurement by three-dimensional transvaginal ultrasound has a higher specificity, which means that it has the ability to better identify the negative cases compared to conventional ultrasound. Three-dimensional transvaginal ultrasound is a helpful tool for diagnosing endometrial cancer in patients with postmenopausal bleeding.

Prognosis of oocytes showing aggregation of smooth endoplasmic reticulum.

Few cytoplasmic dysmorphisms of oocytes have been reported to negatively influence the further fate of the ova. One such anomaly, namely the central aggregation of the smooth endoplasmic reticulum (SER), has recently been associated with suboptimal outcome in a limited number of patients. In order to increase prognostic value, it was decided to prospectively screen all intracytoplasmic sperm injection patients within 1 year for eggs showing aggregations of SER. In addition, all deliveries (obstetric and neonatal data) were analysed. Occurrence of SER cluster was related to duration (P < 0.001) and dosage (P < 0.01) of the stimulation. Fertilization (58.9%) and blastulation rate (44.0%) were lower (P < 0.01) in affected ova compared with unaffected counterparts (77.4 and 87.8%, respectively). Pregnancies in women with affected gametes were accompanied by a higher incidence of obstetric problems (P < 0.01) leading to a non-significant trend towards earlier delivery and significantly reduced birthweight (P < 0.05). It is strongly recommended to avoid transfer of embryos/blastocysts derived from SER cluster-positive gametes. Patients have to be informed that even transfer of sibling oocytes without this anomaly involves a higher risk of detrimental outcome.

Birth weight is lower for survivors of the vanishing twin syndrome: a case-control study.

OBJECTIVE: To compare the outcome of singleton pregnancies originating from a twin gestation with singleton pregnancies originating from a single gestation. DESIGN: Case-control study. SETTING: Women's general hospital in Austria. PATIENT(S): A total of 794 singleton deliveries after IVF/intracytoplasmic sperm injection, including 46 survivors of vanishing twin syndrome (study group) and 92 matched singletons (control group). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Data concerning duration of gestation, mode of delivery, birth weight, neonatal intensive care unit admission, duration of hospitalization, perinatal mortality. RESULT(S): Of all singletons born, 5.8% originated from a twin gestation. Mean (+/- SD) birth weight was significantly higher in the control group (2876.3 +/- 600.5 g vs. 3249.6 +/- 624.5 g). The frequency of low birth weight (26.1% vs. 12.0%) and being small for gestational age (32.6% vs. 16.3%) was significantly lower in the control group. No differences were observed in terms of duration of gestation. CONCLUSION(S): A higher risk for lower birth weight and being small for gestational age for survivors of the vanishing twin syndrome was found. Such pregnancies need to be carefully monitored, and parents must be informed about the associated risks when transferring more than one embryo.