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What is the clinical importance of vitrified-warmed blastocyst transfer timing if performed on days 5, 6 and 7 after detecting the LH surge using urine tests?Between 2013 and 2019, 2080 vitrified-warmed blastocyst transfers in a true natural cycle were performed and later analysed at the Department of Reproductive Medicine, University Medical Centre Maribor, Slovenia. Urine LH tests were performed twice daily to monitor the onset of the LH surge. Vitrified-warmed blastocyst transfer (frozen embryo transfer [FET]) was performed on day 5 (group 1), 6 (group 2) or 7 (group 3) after the LH surge in 18%, 77% and 4% of cycles, respectively. The patient and cycle characteristics among the groups were compared using the Cochran-Mantel-Haenszel test and respective generalized linear mixed models. Propensity score matching was used to adjust for potential differences among the groups.There were no statistically significant differences between groups 1, 2 and 3 in the cycle and patient characteristics, clinical pregnancy rate (38% versus 39% versus 31%), implantation rate (34% versus 36% versus 31%), miscarriage rate (7% versus 9% versus 7%) and delivery rate (31% versus 31% versus 24%). The day of FET after the LH surge detected using a urine test was not significantly associated with live births.The results of the current study suggested that the vitrified-warmed blastocyst transfer could be scheduled on day 5, 6 or 7 after a positive LH urine test without having a significant impact on the clinical outcome.

Purpose: The aim of this study was to compare the reproductive outcomes and live birth rates of natural cycle (NC) and artificial cycle (AC) protocols for endometrial preparation of frozen– thawed embryo transfer (FET). Methods: A total of 1317 NC and 528 AC protocols for endometrial preparation of FET performed during a 3-year period at a tertiary in vitro fertilisation (IVF) clinic were analysed. The clinical spontaneous abortion, pregnancy, and live birth rates were compared. Logistic regression models were constructed to identify the factors that are significantly associated with the live birth and clinical spontaneous abortion rates. Results: A significantly lower clinical spontaneous abortion rate (13.68 % vs. 27.32 %; p < 0.001) and a comparable pregnancy and a significantly higher live birth rate (32.82 % vs. 26.70 %; p < 0.01) were associated with the NC compared to the AC protocol. Independent predictors for live birth were maternal age (odds ratio (OR), 0.94; 95% confidence interval (CI), 0.91–0.98), transfer of morphologically- optimal blastocysts (OR, 1.72; 95% CI, 1.28–2.31), and the method used to prepare the endometrium (OR, 0.63; 95% CI, 0.45–0.88). Independent predictors of clinical spontaneous abortion were the method used to prepare the endometrium (OR, 2.26; 95% CI, 1.39–3.68) and maternal age at the time of FET (OR, 1.07; 95% CI, 1.02–1.13). Conclusions: A better reproductive outcome was observed with the NC protocol; specifically, the clinical spontaneous abortion rate was significantly lower and the live birth rate was significantly higher compared with the AC protocol. Based on better cycle outcomes, patient convenience, and low cost, we suggest using the NC protocol as the first option for FET in patients with regular menses.

Purpose: There are multiple options for the treatment of unexplained infertility. Two of the most commonly used treatments are intrauterine insemination (IUI) and in vitro fertilization (IVF). The aim of our research was to analyze and compare the success rates of IUI and IVF procedures in the treatment of unexplained infertility. Methods: This was a retrospective study including 914 cycles of IUI performed for 355 couples, and 302 IVF cycles performed for 161 couples. All cases involved unexplained infertility and were treated in our department between 2012 and 2014. We analyzed differences in pregnancy, live birth rate, multiple pregnancy rate, and predictive factors for IUI. Results:There was a significant difference between IUI and IVF in terms of cumulative pregnancy and live birth rates after 4 cycles (22.0% vs. 71.8%; p < 0.001 for clinical pregnancy rates and 16.1% vs. 64.8%for live birth rate). Differences between the two techniques in terms of twin live birth rates were not significant (16.5% for IUI vs. 17.6% for IVF; p=0.936). Using logistic regression, we found that the duration of infertility, total sperm count, and the type of stimulation, were significant predictive factors for IUI (p = 0.014, p = 0.036 and p = 0.046, respectively). Conclusion: As expected, according to pregnancy rate, IVF is a better option for the treatment of idiopathic infertility than IUI. However, IUI should not be underestimated since it offers reasonable success rates with significantly less invasiveness. To improve the outcome of treatment for unexplained infertility, we suggest that treatment methods should be chosen with respect to predictive factors.

Endometriosis is a common chronic female reproductive system disease, characterised by the presence of endometrial tissue outside the endometrium and myometrium. It can severely compromise quality of life and have an impact on fertility. Although advances in conservative medical treatment options have been made, surgery is often a necessary part of treatment for this insidious disease.Historically, it was believed that only ovarian endometriosis could be diagnosed non-invasively by an ultrasound examination, while endometriosis at other locations could not be observed. With advances in imaging techniques over the last decades, this has changed dramatically and today deep pelvic endometriosis can be diagnosed non-invasively with high sensitivity and specificity. The aim of this review is to evaluate the contribution of clinical examination, laparoscopy, and non-invasive imaging techniques, mainly transvaginal ultrasound and magnetic resonance imaging, to diagnose deep pelvic endometriosis.Evidence shows that transvaginal ultrasound with high-quality equipment in experienced hands offers high diagnostic accuracy for deep pelvic endometriosis diagnosis. Comprehensive ultrasound examination should be used as a first-line method of choice in diagnostics of women with suspected endometriosisand chronic pelvic pain.

Purpose: A cesarean scar pregnancy is a rare form of ectopic pregnancy in which the gestational sac is implanted in the uterine scar after a previous cesarean section. Early diagnosis is crucial, and transvaginal ultrasound is the most appropriate diagnostic tool. Different management options have been described in the literature; however, there is no consensus regarding optimal treatment due to the rarity of the condition. Case report: We present a case involving a cesarean scar pregnancy which was managed with hysterotomy due to the advanced stage of pregnancy (fetal crown–rump length = 3.5 cm). Conclusion: Early diagnosis of a cesarean scar pregnancy is important to avoid complications and to preserve fertility. Various treatment modalities have been described in the literature, including medical and surgical options.

Purpose: The aim of the study was to establish whether follicular fluid (FF) estradiol (E2) and progesterone (P) measurement could be used to predict the outcome of unstimulated IVF/ICSI cycles. Methods: 91 women underwent 150 unstimulated IVF/ICSI cycles (78 IVF and 72 ICSI). Follicular fluid samples were collected at the time of oocyte recovery. Using the ttest, FF E2 and FF P levels and their ratios (FF P/FF E2) were compared between cycles with successful (with oocyte) and unsuccessful (without oocyte) oocyte recovery, between cycles with and without fertilization and between nonconception and conception cycles. Results: The oocyte recovery rate was 86.7% (123/150), the fertilization rate 68.3% (84/123) and the pregnancy rate per oocyte recovery 14.0% (21/150). The average FF E2 level was 3530 ± 1339 nmol/L, average FF P 20649 ± 9489 nmol/L and average FF P/FF E2 ratio 7.18 ± 6.42. There were no statistically significant differences in FF E2, FF P levels and their ratio between cycles with unsuccessful and successful oocyte recovery, between cycles without and with fertilization, and between nonconception and conception cycles. Conclusion: From the FF E2 and P levels and their ratio, it is not possible to make inferences to the likelihood of oocyte recovery, fertilization and conception in unstimulated IVF/ICSI cycles.

Purpose AI and its machine learning algorithms have proven useful in several fields of medicine, including medically assisted reproduction. The purpose of the study was to construct several predictive models based on clinical data and select the best models to predict IUI procedure outcomes. Methods Clinical data (patient baseline characteristics, sperm quality, hormonal status, and cycle data) from 1029 IUI procedures performed in 413 couples stimulated by clomiphene citrate, letrozole, or gonadotropins were used to build several models to predict clinical pregnancy. The models included ANN, random forest, PLS, SVM, and linear models using the caret package in R. The models were evaluated using ROC analysis by means of random CV on test data. Results Out of the best performing models, the random forest model achieved an AUC of 0.66, a sensitivity of 0.432, and a specificity of 0.756. This performance was followed by the PLS model, which achieved a sensitivity of 0.459 and specificity of 0.734. The other models achieved significantly lower AUCs. When adjusting the predictive cutoff value, confusion matrices show that clinical pregnancy is twice as likely in the case of positive prediction. Conclusion Among the compared methods, the random forest and PLS models demonstrated superior performance in predicting the clinical outcome of IUI. With additional research and clinical validation, AI methods may be successfully used in improving patient selection and consequently lead to better clinical results.

We present a 26-year-old primigravida with rudimentary horn pregnancy rupture at 14 weeks of pregnancy. Uterine anomaly was first diagnosed at the time of nuchal translucency scan and was presumed to be a bicornuate uterus with normal intrauterine pregnancy in the right horn. One day later, she was admitted to our department with abdominal pain, shortly leading to massive hemoperitoneum and hypovolemic shock. Uterine rupture was confirmed ultrasonically, followed by immediate laparotomy. Ruptured rudimentary horn with already expulsed pregnancy was encountered during surgery. Despite significant advances in ultrasonography, diagnosis of prerupture stage remains controversial. However, high mortality of the condition should ensure low threshold for surgical exploration.

Does laser-induced artificial blastocoel collapse result in better blastocyst cryopreservation survival and a higher live birth rate (LBR) in comparison with intact counterparts?Half of the supernumerary blastocysts from IVF cycles were randomly selected before vitrification for laser-induced artificial collapsing or vitrification in intact form. A matched case-control study of first transfers of single blastocysts artificially collapsed (case) or intact (control) before vitrification was conducted. Controls were matched to cases on a 1:1 ratio by female age, parity, fresh and vitrified cycle protocol, blastocyst age and quality, resulting in 309 case-control pairs.The two groups were comparable in terms of their characteristics. Survival rates in the case and control groups (97.8% and 95.7%; P = 0.133) were comparable, but the optimal survival rate was higher in the case group (78.2% and 69.3%; P = 0.03). Clinical pregnancy rates (38.2% and 35.3%; P = 0.518), miscarriage rates (15.2% and 22%; P = 0.190), LBR per transfer (32.4% and 27.5%; P = 0.221) and LBR per warmed blastocyst (31.6% and 26.3%; P = 0.137) were not statistically different between the case and control groups. No significant difference in preterm births (11.1% versus 15.7%), birthweights (3333 ± 723 g versus 3304 ± 609 g) or sex ratio (49.3% versus 50.7% boys) was observed between the two groups. No major malformations were detected in the study population.Compared with vitrification of intact blastocysts, collapsed blastocysts resulted in a significantly higher optimal survival rate, and although they resulted in a 5% higher LBR, this was not significant for the chosen sample size. Neonatal outcomes were comparable in the two groups.

Study question Does laser-induced artificial blastocoel collapse result in better blastocyst cryopreservation survival and higher live birth rate (LBR) in comparison with intact counterparts? Summary answer Compared to vitrification of intact blastocysts, collapsed blastocysts resulted in higher survival and for 5% higher LBR. Neonatal outcomes were comparable in both groups. What is known already Blastocysts have long been considered a stage that is suboptimal for freezing-thawing procedures due to their high fluid content and different cell types. The development of a modified vitrification technique has enabled blastocysts to better survive cryopreservation compared to a slow freezing procedure. Many studies on the optimization of cryopreservation of blastocysts have mentioned the need for artificial collapsing of the blastocoel prior to cryopreservation, thereby reducing the risk of intracellular ice-crystals formation. However, the effectiveness of artificial collapsing on blastocyst survival rate, single vitrified-warmed blastocyst transfer (SVBT) outcome and on safety of such intervention remains to be confirmed. Study design, size, duration A retrospective matched case-control study of transfers of single blastocysts being artificially collapsed (case) or intact (control) before vitrification. A sample size of 306 cycles in both arms was needed to achieve 80% power to detect a difference between the groups of 10% with P Participants/materials, setting, methods Artificial collapsing was introduced into clinical practice gradually. In fresh IVF cycles (performed in university clinic from 2012 until 2014) with supernumerary blastocysts, half of the blastocysts were randomly selected before vitrification for laser-induced artificial collapsing. The other half was vitrified in intact form. Only the first transfers of a single vitrified-warmed blastocyst (n = 818) were included in the study. By matching, 309 pairs of collapsed (study) and intact (control) SVBTs were identified. Main results and the role of chance Both groups were comparable by their characteristics in indications, female age, type and length of ovarian hyperstimulation, insemination method in fresh cycle, protocol for warmed blastocyst transfer, blastocyst quality and day of blastocyst vitrification. Survival rates in case and control group ((309/316) 97.8% and (309/323) 95.7%; P = 0.13) were comparable, but optimal survival rates (100% survival and re-expansion after warming) was significantly higher in artificial collapse group ((247/316) 78.2% and (225/323) 69.7%; P = 0.01). Clinical pregnancy rates ((120/309) 38.8% and (110/309) 35.6%; P = 0.4), miscarriage rates ((15/120) 12.5% and (24/110) 21.8%; P = 0.06) and LBR per transfer ((100/309) 32.4% and (85/309) 27.5%; P = 0.19) or LBR per warmed blastocyst ((100/316) 31.6% and (85/323) 26.3%; P = 0.14) were not statistically different between case and control groups. Since the study was powered to detect a 10% difference, the possibility of type 2 error cannot be excluded. Perinatal outcomes were available for 175 live births. There were 10.5% (10/95) preterm births in the study group vs. 16.3% (13/80) in control group (P > 0.05). Birth weights (3,308 g (SD 592 g) vs 3,308 g (SD 738 g) and sex ratio (50.7% vs 49.2% boys) were also comparable between both groups (P > 0.05). There were no major malformations detected in the study population. Limitations, reasons for caution The research is retrospective, but the cycles from both groups were performed in the same time period. The groups were balanced according to all possible confounders. Blastocysts for vitrification were first categorized by quality groups and embryos from each category were randomized for collapsing or for remaining intact. Wider implications of the findings: No significant difference was found in live births by this sample size. Nevertheless, increasing the success by 5% with the introduction of artificial collapsing can be an important step towards optimizing of blastocyst cryopreservation. To confirm a 5% improvement in results, a sample size of > 2500 cases would be needed. Trial registration number The study has been approved by the National Ethics Committee of the Republic of Slovenia (0120–204/2016–2).

Purpose The purpose of this study was to find out the most important prognostic factors for achieving a pregnancy after in vitro fertilization (IVF) in women with history of repeated unsuccessful IVF attempts. Methods We analyzed factors affecting pregnancy rate in a retrospective study including 429 IVF/ICSI cycles performed in women younger than 40 years with at least three previous consecutive failed IVF/ICSI attempts. Results Clinical pregnancy was observed in 140/429 (32.6%) cycles. Clinical pregnancy rate (CPR) was significantly higher in cycles with LEI compared to cycles without LEI before embryo transfer (44.4 vs 26.54%, p = 0.007). The CPR was also higher in cycles with day 5 blastocyst- compared with day 3 cleavage-stage embryo transfers (45.51 vs 26.54%, p

PURPOSE: The aim of the study was to compare the levels of angiogenic markers and markers of placentation between pregnancies conceived with fresh (ET) and vitrified-warmed blastocyst transfer (FET). METHODS: Women with singleton pregnancies resulting from fresh ET or FET during the period between 2013 and 2017 were included in this prospective observational study. Fresh ET was performed in a stimulated and FET in natural cycle. At 6–7 weeks of gestation, after ultrasound confirmation of a single gestational sac with a viable embryo, serum levels of free β-hCG, pregnancy-associated plasma protein A (PAPP-A), placental growth factor (PIGF) and fms-like tyrosine kinase (sFlt-1) were measured. Data on the patients’ characteristics, pregnancy complications and outcomes were collected from a questionnaire and National Perinatal Information System of Slovenia. RESULTS: Among 211 pregnancies, 126 were achieved with fresh ET and 85 with FET. There were no significant differences in perinatal outcome, pregnancy complication and PIGF level between the fresh ET and FET group. Women achieving pregnancy with FET had significant higher levels of free β-hCG (40.20 ± 30.62 IU/L vs. 28.74 ± 23.52, p = 0.002), PAPP-A (0.09 ± 0.06 vs. 0.06 ± 0.05 IU/L, p = 0.004) and sFlt-1 (596.19 ± 283.06 vs. 436.53 ± 248.23 pg/L, p

AI and its machine learning algorithms have proven useful in several fields of medicine, including medically assisted reproduction. The purpose of the study was to construct several predictive models based on clinical data and select the best models to predict IUI procedure outcomes.Clinical data (patient baseline characteristics, sperm quality, hormonal status, and cycle data) from 1029 IUI procedures performed in 413 couples stimulated by clomiphene citrate, letrozole, or gonadotropins were used to build several models to predict clinical pregnancy. The models included ANN, random forest, PLS, SVM, and linear models using the caret package in R. The models were evaluated using ROC analysis by means of random CV on test data.Out of the best performing models, the random forest model achieved an AUC of 0.66, a sensitivity of 0.432, and a specificity of 0.756. This performance was followed by the PLS model, which achieved a sensitivity of 0.459 and specificity of 0.734. The other models achieved significantly lower AUCs. When adjusting the predictive cutoff value, confusion matrices show that clinical pregnancy is twice as likely in the case of positive prediction.Among the compared methods, the random forest and PLS models demonstrated superior performance in predicting the clinical outcome of IUI. With additional research and clinical validation, AI methods may be successfully used in improving patient selection and consequently lead to better clinical results.

Background and objective: Automated follicle detection in ovarian ultrasound volumes remains a challenging task. An objective comparison of different follicle-detection approaches is only possible when all are tested on the same data. This paper describes the development and structure of the first publicly accessible USOVA3D database of annotated ultrasound volumes with ovarian follicles. Methods: The ovary and all follicles were annotated in each volume by two medical experts. The USOVA3D database is supplemented by a general verification protocol for unbiased assessment of detection algorithms that can be compared and ranked by scoring according to this protocol. This paper also introduces two baseline automated follicle-detection algorithms, the first based on Directional 3D Wavelet Transform (3D DWT) and the second based on Convolutional Neural Networks (CNN). Results: The USOVA3D testing data set was used to verify the variability and reliability of follicle annotations. The intra-rater overall score yielded around 83 (out of a maximum of 100), while both baseline algorithms pointed out just a slightly lower performance, with the 3D DWT-based algorithm being better, with an overall score around 78. Conclusions: On the other hand, the development of the CNN-based algorithm demonstrated that the USOVA3D database contains sufficient data for successful training without overfitting. The inter-rater reliability analysis and the obtained statistical metrics of effectiveness for both baseline algorithms confirmed that the USOVA3D database is a reliable source for developing new automated detection methods.

The aim of the study was to determine predictive factors for live birth after in vitro fertilization with autologous oocytes in women ≥40 years of age.Authors conducted a retrospective analysis of in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles performed at the Department of Reproductive Medicine and Gynecologic Endocrinology, University Medical Centre Maribor, Slovenia between January 2006 and December 2015 in women aged 40 or more. The characteristics of patients and cycles were compared regarding live birth as the final outcome.A total of 1920 IVF/ICSI cycles with egg retrieval in women ≥40 years of age were performed leading to 1591 embryo transfers. The live birth rate per embryo transfer was 17.3% at 40, 11.6% at 41, 8.2% at 42, 7.9% at 43, 1.9% at 44 and 0.0% at ≥45 years of age. The multivariate logistic regression model showed that besides women's age (OR 0.66, 95% CI: 0.55-0.78), the number of previous cycles (OR 0.88, 95% CI: 0.82-0.95), number of good quality embryos on day 2 (OR 1.19, 95% CI: 1.05-1.36), number of embryos transferred (OR 1.57, 95% CI: 1.19-2.07) and day 5 embryo transfer (OR 2.21, 95% CI: 1.37-3.55) were also independent prognostic factors for live birth.The chance of in vitro fertilization success in women ≥40 years of age should not be estimated only on the woman's age, but also on other predictive factors: number of previous cycles, number of good quality embryos on day 2, number of transferred embryos and blastocyst embry transfer.Namen raziskave je bil odkriti napovedne dejavnike za živorojenost po postopku zunajtelesne oploditve z lastnimi jajčnimi celicami pri ženskah, starih 40 let in več.Avtorji so v retrospektivno analizo zajeli postopke zunajtelesne oploditve, ki so jih opravili na Oddelku za reproduktivno medicino in ginekološko endokrinologijo Univerzitetnega kliničnega centra Maribor od januarja 2006 do decembra 2015 pri bolnicah, starih 40 let ali več. Primerjali so značilnosti bolnic in postopkov, ki so se končali s porodom, s tistimi, kjer je bil postopek neuspešen.Pri bolnicah, starih 40 let in več, so naredili 1.920 aspiracij foliklov, v 1.591 postopkih pa so prenesli zarodke v maternično votlino. Delež živorojenih na prenos zarodka je bil v starosti 40 let 17,3 %, v starosti 41 let 11,6 %, pri 42 let starih ženskah 8,2 %, v starosti 43 let 7,9 %, pri 44-letnih 1,9 % in 0,0 % v starosti ≥45 let. Multivariatni logistični regresijski model je pokazal, da so ob starosti ženske (RR 0,66, 95 % CI: 0,55–0,78) neodvisni napovedni dejavniki za porod še število predhodno opravljenih postopkov (RR 0,88, 95 % CI: 0,82– 0,95), število kakovostnih zarodkov na dan 2 (RR 1,19, 95 % CI: 1,05-1,36), število prenesenih zarodkov (RR 1.57, 95% CI: 1,19–2,07) in število prenosov 5 dni starih zarodkov (RR 2,21, 95 % CI: 1,37–3,55).Pri napovedi uspešnosti postopkov zunajtelesne oploditve pri ženskah, starih ≥40 let, je treba poleg starosti upoštevati tudi druge napovedne dejavnike: število predhodnih postopkov, število zarodkov dobre kakovosti na dan 2, število prenesenih zarodkov in prenos blastocist.

Background This study evaluated the influence of menstrual cycle length, menstrual cycle variability and predicted luteal phase length on the success of vitrified-warmed blastocyst transfer in natural menstrual cycle using progesterone for luteal phase supplementation. Methods Consecutive women undergoing vitrified-warmed blastocyst transfer in natural menstrual cycle between January 2013 and December 2015 were included in this retrospective study. Patients’ characteristics, clinical data and data about menstrual cycle length in the last year were collected from our database. Predicted luteal phase length (LPL) was defined as the period starting at ovulation (one day after positive urinary LH test) and ending on the last day before predicted menses, based on women’s usual, minimal and maximal menstrual cycle length data. Logistic regression was used to identify the predictors significantly associated with live-birth. Results A total of 1195 FETs (frozen-thawed embryo transfers) resulted in 457 (38.24%) clinical pregnancies, 82 (17.94%), miscarriages and 371 live births (31.04%). There were no statistically significant differences in menstrual cycle length, menstrual cycle variability, day of LH surge, day of FET and predicted LPL between FET cycles resulting in live birth and those not resulting in live birth. In the multivariate logistic regression model, only women’s age (OR 0.93, 95% CI: 0.90–0.96), transfer of morphologically optimal blastocysts (OR 2.17, 95% CI: 1.59–2.94) and endometrium thickness (OR 1.10, 95% CI: 1.03–1.17) were important independent prognostic factors for live birth. Conclusion Menstrual cycle length, menstrual cycle variability and predicted LPL do not seem to be an important factor influencing live birth after FET in natural cycles with progesterone supplementation. Results of our study suggest that FET should not be cancelled if LH surge is detected before or after the predicted period in natural cycle with progesterone supplementation.

The aim of the present study was to evaluate if the live birth predictive values of β-hCG levels differ in fresh and vitrified-warmed blastocyst transfer cycles.In the retrospectively designed study, 775 cycles with positive β-hCG values 13 days after fresh blastocyst transfer (fresh ET; n = 568) or vitrified-warmed blastocyst transfer (FET; n = 207) were selected for analysis. Average β-hCG levels stratified according to pregnancy outcome (biochemical pregnancy, spontaneous abortion, ectopic pregnancy, and singleton or twin birth) were compared between fresh ET and FET cycles. To determine the optimal sensitivity and specificity of β-hCG levels for live birth prediction, a ROC curve was constructed. Fisher's exact test was used to compare the positive predictive values (PPV).Average β-hCG levels stratified according to pregnancy outcome were not statistically different between fresh ET and FET cycles. In fresh ET and in FET group, the β-hCG levels were significantly higher in pregnancies resulting in live birth compared to non-viable pregnancies (1,035 vs. 462 IU/L, p 0.001 and 968 vs. 411 IU/L, p 0.001). Optimal cut-off level for live birth prediction was 495 IU/L (sensitivity 83.0 %, specificity 71.8 %) after ET and 527 IU/L (sensitivity 80.0 % and specificity 76.6 %) after FET. The PPV for live birth rate in the groups after ET and FET were 90.6 % and 84.9 % respectively, without statistically significant difference (p 0.05).Beta-hCG levels after fresh and vitrified-warmed blastocyst transfer are equally predictive for pregnancy outcome. Clinicians can be encouraged to interpret β-hCG results in the same manner.

The testicular sperm from biopsy and frozen/thawed tissue are frequently immotile. The purpose of our retrospective study was to assess the effect of short exposure of testicular samples with only immotile sperm to pentoxifylline (PF)-sperm motility stimulator. In 77 of 294 (26.2%) testicular sperm ablation/testicular sperm extraction-intracytoplasmic sperm injection (TESA/TESE-ICSI) cycles in patients with azoospermia, only immotile sperm were found in biopsies even after 2 hours of incubation of tissue in the medium. These 77 cycles were divided into 2 groups. In group 1 (cycles between 1999 and 2001; n = 30), ICSI was performed with untreated immotile sperm. In group 2 (cycles between 2002 and 2004; n = 47), immotile testicular sperm were treated for 20 minutes with pentoxifylline (PF) (1.76 mM) before ICSI. Both groups had the same proportion of ICSI cycles with fresh, frozen/thawed, and aspirated testicular sperm. The overall pregnancy rate of TESA/TESE-ICSI did not vary during the study period. In 45 of 47 (95.7%) testicular samples with total immotility, the sperm started to move 20 minutes after PF treatment. The mean time required for ICSI was shortened in the PF group (30 minutes [minimum 10, maximum 90] vs 120 minutes [minimum 60, maximum 240]) due to easier identification of motile sperm. In comparison with the nontreated group, the PF group had a higher fertilization rate (66% vs 50.9%; P < .005) and mean number of embryos per cycle (4.7 ± 3.3 vs 2.7 ± 2.1; P < .01). The clinical pregnancy rate per cycle in PF and non-PF groups was 38.3% and 26.7%, respectively. By using PF in cases of only immotile testicular sperm we can cause movement of testicular sperm, allow easier identification of vital sperm, shorten the procedure, improve fertilization rates, and increase the number of embryos.

After prolonged culture of human embryos, the expanded blastocysts with oval inner cell mass (ICM) and cohesive trophectoderm (TE) are preferably selected for transfer. In cycles with poor embryonic development, the selection has to be done from among suboptimal blastocysts for which no grading system exists. In this study, 1396 transferred blastocysts and morulae were classified into eight morphologic categories. The B1 category constituted the optimal blastocysts. The other categories were characterized by different deviations from optimal blastocysts: cytoplasmic fragments and necrosis in TE (B2), unexpanded blastocoele (B3), non-compact or small ICM (B4), fragments in TE and ICM (B5), up to 20% excluded blastomeres (B6), necrotic TE and ICM (B7), and more than 20% excluded cells from blastocysts (B8). The live birth rate was calculated from blastocysts with known outcome after transfer (88.9% transferred blastocysts). The birth rate declined from B1 to B8 by the same order and was: 45.2, 32.8, 26.9, 23, 17.7, 16.7, 7.7 and 1.2% respectively. Normal ICM was recognized as the most important parameter for implantation. There was a strong relation between such ordered morphology categories and implantation capacity (P < 0.0001). Such a grading system is helpful in selecting the best of all available day-5 embryos for transfer.

Objective To establish whether we might predict the outcome of unstimulated in-vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles with quantitative indices of perifollicular blood flow assessed with three-dimensional (3D) reconstruction of power Doppler images. Methods This prospective study included an analysis of 52 unstimulated cycles. Color and power Doppler ultrasound examinations of a single dominant preovulatory follicle were performed on the day of oocyte pick-up. With 3D reconstruction and processing, quantitative indices were obtained i.e. the percentage of volume showing a flow signal (VFS) inside a 5-mm capsule of perifollicular tissue and the percentage of VFS of each of the three largest vessels in this capsule. These indices as well as pulsed Doppler indices were compared between the groups of cycles with different outcomes using a one-way ANOVA test. Results In nine cycles no oocyte was retrieved (Group A), in seven cycles no fertilization occurred (Group B) and in 30 cycles no implantation occurred (Group C). Six cycles resulted in pregnancy (Group D). There were no statistically significant differences in pulsed and power Doppler indices between these groups. However, the percentage of VFS in the capsule was higher than average in cycles with implantation (19.22 ± 16.82 vs. 12.42 ± 8.89, NS) and the percentage of VFS in the main vessel exhibited lower than average values in cycles with implantation (20.66 ± 10.05 vs. 39.84 ± 20.15), but only reached borderline statistical significance (F = 2.457, P = 0.074). Conclusion It can be hypothesized that the follicles containing oocytes able to produce a pregnancy have a distinctive and more uniform perifollicular vascular network. Copyright © 2003 ISUOG. Published by John Wiley & Sons, Ltd.

This prospective randomized study compared the effectiveness of a flexible single-dose gonadotrophin-releasing hormone (GnRH) antagonist (cetrorelix) and a single-dose long GnRH agonist (goserelin) protocol for ovarian stimulation in IVF/intracytoplasmic sperm injection (ICSI) cycles. All patients from the waiting list were successively included in the study, pre-programmed with an oral contraceptive, and randomized into goserelin and cetrorelix groups. Depending on the date on which their menstrual period started, patients took oral contraceptives for one or two cycles. Ultimately, 236 patients in the first group received a single dose of depot preparation of goserelin and 224 patients received a single 3 mg dose of cetrorelix in the late follicular phase, when the mean follicle diameter exceeded 12 mm. The mean number of ampoules of FSH and the duration of stimulation was statistically significantly lower in the cetrorelix group than in the goserelin group (25.9 versus 34.5, and 9.6 versus 12.2 days, P0.01). The mean number of oocytes retrieved was similar (6.7 +/- 4.5 versus 7.2 +/- 4.6, NS). Similar results were observed in fertilization rates, blastulation rates and blastocyst transfer rates in both groups. Clinical pregnancy and delivery rates per cycle were higher in the goserelin group (34.3 and 30.1%) than in the cetrorelix group (31.9 and 28.3%), but the differences were not statistically significant. The flexible single-dose GnRH antagonist protocol is an advantageous alternative to the long GnRH agonist protocol, with similar efficacy, shorter duration, a significant reduction in the number of FSH ampoules used and without the menopause-like effects of the GnRH antagonist.

To compare blood coagulation parameters between pregnant women with vaginal bleeding in the first trimester of pregnancy and pregnant women with normal pregnancy in the first trimester.A prospective controlled study of 98 women in the first trimester of vital pregnancy was conducted at the University Medical Centre Maribor, Slovenia. The study group comprised women with vaginal bleeding (n=50) while the control group women with normal pregnancy, admitted for artificial abortion (n=48). Prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen concentration, number of platelets, hemogram, coagulation factor VIII (FVIII) and von Willebrand factor (VWF) activity were compared between the 2 groups.No significant between-group differences were detected in mean PT, fibrinogen concentration, FVIII, and VWF activity. Mean aPTT was significantly higher in the control group than the study group (32.47 versus 30.46 seconds; P0.05). The mean number of platelets was significantly lower in the study group than the control group (181.69 versus 203.52×10(9)/L; P0.05). All measured coagulation parameters, except VWF activity, were within normal ranges.Coagulation abnormalities are rarely the cause of vaginal bleeding in the first trimester of pregnancy among women with no previous symptoms of bleeding disorders.

Objective: To determine whether extended culture of embryos to blastocysts has any benefit in cycles with only one or two created embryos. Design: Retrospective analysis of cycles comparing outcomes of day 2 and day 5 transfers. Our day 2 group was from the year 1999 and our day 5 group, from the year 2000. Setting: Assisted reproductive technology program of a teaching hospital. Patient(s): All patients, irrespective of age, who had developed one or two embryos. Intervention(s): Stimulated IVF, intracytoplasmic sperm injection, or testicular sperm extraction and intracytoplasmic sperm injection cycles with 2-day culture in universal IVF medium (n = 133) or 5-day culture in BlastAssist media (MediCult, Jyllinge, Denmark; n=132). Main Outcome Measure(s): Pregnancy, implantation, and take-home baby rates. Result(s): In the groups of 2-day and 5-day culture, embryo transfer was performed in 98% and in 57% of cycles, respectively. However, the total implantation rate per created embryo (18% vs. 18%), the pregnancy rate per cycle (23% vs. 21%), and the take-home baby rate (69.4% vs. 71.4%) did not differ between the day 2 and day 5 groups. Conclusion(s): Extended culture of embryos does not improve or decrease their capacity for implantation but only allows for better selection and is therefore not necessary in cycles with fewer than three embryos.

Purpose: The purpose was to test the adequacy of unstimulated cycles for intracytoplasmic sperm injection (ICSI) and to evaluate implantation and pregnancy rates in three different age groups.

BACKGROUND: The aim of the study was to test the influence of 2- and 5-day cultivation of a single oocyte on the pregnancy rate in a non-stimulated cycle. METHODS: A retrospective chart review of 391 consecutive patients undergoing IVF and intracytoplasmic sperm injection in unstimulated cycles was performed. The embryos were kept in MediCult universal IVF medium for day 2 transfers and in BlastAssist System for day 5 transfers. RESULTS: The oocyte recovery rate in the group for 2-day cultivation and in the group for 5-day cultivation was similar, being 79.4 (162/204) and 83.6% (154/187) respectively. The same is true of the fertilization rate (73.8 versus 77.7%). The blastulation rate was 52.8%. The embryo transfer rate per cycle was higher when day 2 embryos were transferred: 64.8% (105/162) compared with 35.7% (55/154) if blastocyst-stage embryos were transferred. The pregnancy rate per transferred embryo was higher when a blastocyst was transferred (40.0%) instead of a day 2 embryo (23.8%). CONCLUSION: The expected pregnancy rate calculated per embryo available on day 2 of cultivation was similar in both groups (23.8 versus 22.2%) and it was not affected by oocyte culture to the blastocyst stage.

Objectives The aim of the study was to investigate whether endometrial thickness, endometrial pattern, endometrial movement and serum estradiol and progesterone affect the outcome of in vitro fertilization. Methods Prospectively collected data of endometrial thickness, endometrial pattern and subendometrial activity were analyzed in 122 consecutive in vitro fertilization cycles. All measurements were made on the day of hCG administration (day −2), day of embryo transfer (day +2), day +6 and day +12. Results It would appear that pregnant women tend to have a thicker endometrium on day +12 than non-pregnant women. There appears to be no appreciable difference between pregnant and non-pregnant women in endometrial movement and thickness, nor in serum estradiol and progesterone on day +2 and day +6. In combining three echographic variables (thickness, pattern and movement) and hormone level (estradiol and progesterone), only progesterone on day +12 could be used to predict the outcome. Conclusions Subendometrial contractility plays no important role in implantation on the day of embryo transfer or 4 days later. Copyright © 2001 International Society of Ultrasound in Obstetrics and Gynecology

Purpose:The aim of the study was to find whether inferences to the possible success of natural IVF/ICSI cycles could be drawn from the estradiol (E2) pattern. Methods:Sixty-eight women who underwent oocyte recovery in 98 natural cycles were recruited for the study. Daily serum E2 was measured in the preovulatory phase (−3 to +2 day). The E2pattern was compared among four groups: Group A, unsuccessful egg retrieval; Group B, no fertilization; Group C, no implantation; and Group D, implantation. Results:There was no difference in mean E2levels between groups. Only the ratio of E2on day +1/E2on day 0 was significantly lower in conception cycles in comparison with nonconception cycles. In cycles with a decreased E2level on day +1, only the implantation rate was significantlly higher in comparison with cycles with an increasing E2level. Conclusions:From the E2pattern it is possible to make inferences about the likelihood of implantation but not the fertilization or oocyte recovery success.

Objective: To predict the risk of premature ovulation and possibility of pregnancy in natural IVF/ICSI cycles on the basis of the estradiol (E2) level on the day of hCG injection and on the day after. Design: A prospective study. Setting: Hospital research program. Patient(s): One hundred sixty-four women undergoing 305 IVF/ICSI natural cycles. Intervention(s): Serum E2 levels were measured ∼12 h before (day 0) and 12–17 h after hCG administration (day 1). Main Outcome Measure(s): E2 levels on day 0 and day 1, the ratio of the day 1 to day 0 levels, and cycle outcome. Result(s): In cycles with premature ovulation and in conception cycles, the average E2 level on day 0 was statistically significantly higher than in other cycles, whereas the E2 ratio was statistically significantly lower. Multiple logistic regression was used to determine the connection of the E2 level on day 0 (B0 = −0.742, B = 2.147, P = .01) and the E2 ratio (B0 = −0.742, B = −3.135, P

Objective: To evaluate the success of a protocol for controlled ovarian hyperstimulation allowing patient self-selection into groups for ovulation stimulation planned 8 weeks and more in advance following cycle synchronization, drug self-administration as well as a reduced number of folliculometries. Methods: A total of 714 patients received the same stimulation protocol. In 260 cases GnRH-a was applied daily and in 454 as depot. In all patients FSH-HP was self-administered subcutaneously for ovarian stimulation. In 316 patients IVF and in 398 patients ICSI was performed. Results: The delivery rate per started cycle was higher in patients receiving depot GnRH-a in the IVF and ICSI group (30.2 vs. 23.4) than in those receiving subcutaneous GnRH-a (20.2 vs. 22.1). Conclusion: Programming of the IVF/ICSI cycle greatly simplifies treatment. A comparison of pregnancy rate and delivery rate per cycle between depot and subcutaneous daily application of GnRh-a did not confirm any statistically significant difference.