Laparoscopic abdominal cerclage after radical vaginal trachelectomy.

BACKGROUND: The incidence of cervical cancer (CC) in Slovenia in 2011 was 13.2 per 100,000 women. The treatment of early stages of invasive cervical carcinoma involves several surgical techniques. In this article the authors would like to present a new combination of two methods which help to preserve fertility and to improve pregnancy outcome. The first procedure, radical vaginal trachelectomy (RVT), begins with laparoscopic pelvic lymphadenectomy. All suspicious lymph nodes are sent to frozen section. If those lymph nodes are negative, the procedure continues vaginally. Almost the entire cervix is removed with parametria and vaginal cuff. Permanent cerclage stitch is applied and covered with vagina on what is left of uterus. Second procedure, laparoscopic abdominal cerclage (LAC), begins with pneumoperitoneum. Mersilene tape is introduced in the abdominal cavity and placed through the visceral peritoneum at the isthmic part of the uterus with a Berci's needle. It is knotted and remains permanently. MATERIALS AND METHODS: For the first procedure all the patients with confirmed cervical carcinoma (FIGO Stage IA1, IA2, and IB1) and with the desire for fertility were recruited. For the second procedure, all the patients after RVT and after miscarriage after 14th week of gestation were recruited. RESULTS: RVT was performed in 15 patients and laparoscopic abdominal cerclage in three of them (21.5%). All three patients achieved pregnancies and after 36th weeks of gestation delivered by cesarean section (100%). CONCLUSIONS: RVT alone is an indication for LAC. Considering its success, LAC should be performed before any miscarriage.

A double blind randomised placebo controlled study of propolis (bee glue) effectiveness in the treatment of severe oral mucositis in chemotherapy treated children.

OBJECTIVES: Chemotherapy-induced oral mucositis (OM) is a debilitating side effect. In addition to standard therapy, patients often use complementary and alternative medicine to treat OM. DESIGN: Double blind randomised placebo controlled study assessing propolis (bee glue) efficacy for chemotherapy-induced severe OM treatment. SETTING: University Children's Hospital, University Medical Centre Ljubljana, Ljubljana, Slovenia. INTERVENTIONS: Paediatric patients undergoing chemotherapy were randomly assigned to propolis (n=19) or placebo groups (n=21). Patients were introduced to a unified oral care protocol and asked to apply propolis or placebo to vestibular mucosa twice daily. Oral mucosa was assessed with the Oral Assessment Guide (OAG) twice a week when the patients were in hospital. Patients were followed for the period of the chemotherapy or for the first 6 months of the chemotherapy. An OAG score of 3 was considered to be severe OM and analysed. MAIN OUTCOME MEASUREMENTS: Three dependent variables (a) OM episode frequency, (b) mean number of assessment visits, at which an OAG 3 score was noted, expressing mean OM duration, (c) mean number of OAG 3 scores expressing mean OM severity) were reduced to a single variable using principal component analysis. A new variable (FDS) was used as the dependent variable in ANCOVA model analysis to show the differences between study groups. RESULTS: Severe OM was seen in 42% and 48% of patients in the propolis and placebo group, respectively. FDS was not statistically significant between study groups (p=0.59). CONCLUSIONS: According to our study results, propolis cannot be recommended for severe OM treatment.

Septate, subseptate and arcuate uterus decrease pregnancy and live birth rates in IVF/ICSI.

A retrospective matched-control study to evaluate the effect of uterine anomalies on pregnancy rates after 2481 embryo transfers in conventionally stimulated IVF/intracytoplasmic sperm injection (ICSI) cycles. The study group of 289 embryo transfers before and 538 embryo transfers following hysteroscopic resection of a uterine septum was compared with two consecutive embryo transfers in the control group. Groups were matched for age, body mass index, ovarian stimulation, embryo quality, IVF or ICSI and infertility aetiologies. Number of embryos transferred, embryo quality and absence of uterine anomalies significantly predicted the pregnancy rates in the study group: odds ratios (OR) 1.7, 2.6 and 2.5, respectively (P<0.001). Pregnancy rates after embryo transfer before hysteroscopic metroplasty were significantly lower, both in women with subseptate and septate uterus and in women with arcuate uterus compared with controls. If two or three embryos with at least one best-quality embryo were transferred, the differences were 9.6% versus 43.6%, OR 7.3 (P<0.001) and 20.9% versus 35.5%, OR 2.1 (P<0.03), respectively. Differences in terms of live birth rates were even more evident: 1.9% versus 38.6%, OR 32 (P<0.001) and 3.0% versus 30.4%, OR 14 (P<0.001). After surgery, the differences disappeared. This retrospective matched control study evaluated the influence of septate, subseptate and arcuate uterus on pregnancy and live birth rates after 2481 in conventionally stimulated IVF/intracytoplasmic sperm injection (ICSI) cycles. The study group included 827 embryo transfers (289 embryo transfers before and 538 embryo transfers following hysteroscopic resection of uterine septum ans was compared with two consecutive mebryo transfers in the control group. Both groups were matched by age, body mass index, stimulation protocol, quality of embryos, use of IVF or ICSI, and infertility aetiologies. Multivariate logistic regression analysis of the study group showed that the number of embryos, embryo quality and the absence of uterine anomalies significantly predicted the pregnancy rates: odds ratios (OR) 1.7, 2.6, and 2.5, respectively (P<0.001). The pregnancy and live birth rates before surgery were lower compared with controls, both in women with subseptate or septate uterus and in women with arcuate uterus. If two or three embryos with at least one best quality embryo were transferred, the differences in terms of pregnancy rates were 9.6% versus 43.6%, OR=7.3 (P<0.001) and 20.9% versus 35.5%, OR=2.1 (P<0.03), respectively. The differences in terms of live birth rates were even more evident: 1.9% versus 38.6%, OR=32 (P<0.001) and 3.0% versus 30.4%, OR=14 (P<0.001). After surgery, the differences disappeared. Negative impact of uterine anomalies on pregnancy and on live birth rates are two important arguments for treating uterine anomalies in infertile women.

The outcome of singleton pregnancies after IVF/ICSI in women before and after hysteroscopic resection of a uterine septum compared to normal controls.

OBJECTIVE(S): To evaluate the effect of hysteroscopic resection of a large uterine septum (Class V according to the American Fertility Society (AFS) classification) and of a small partial uterine septum (Class VI according to AFS classification or arcuate uterus) on the abortion rate in pregnancies after IVF and ICSI. STUDY DESIGN: The retrospective matched control study included 31 women who conceived following IVF or ICSI before hysteroscopic resection of a large (12 women) or small partial (19 women) uterine septum and 106 women who conceived following IVF or ICSI after hysteroscopic resection of a large (49 women) or small partial (57 women) uterine septum. For each pregnancy in the study group, we found two consecutive pregnant control women from the IVF/ICSI registry who had a normal uterus and were matched for age, BMI, stimulation protocol and the use of IVF or ICSI and for various infertility causes. The abortion/pregnancy rate was the main outcome measure. Data on the septum length were obtained during hysteroscopic resection by comparing the length of the 1.4 cm long yellow tip of the electric knife to the length of the resected septum. RESULTS: The abortion rate before hysteroscopic metroplasty was significantly higher, both in women with a small partial septum (78.9% before resection vs. 23.7% in the normal controls, OR 12.08) and a large septum (83.3% before resection vs. 16.7% in normal controls, OR 25.00) compared to women with a normal uterus. After the surgery, the abortion rate was comparable to the abortion rate in women with normal uterus: in both women with a small partial and women with a larger septum. CONCLUSION(S): Similar to a large uterine septum, a small partial uterine septum is an important and hysteroscopically preventable risk factor for spontaneous abortion in pregnancies after IVF and ICSI.

Age, oestradiol and blastocysts can predict success in natural cycle IVF-embryo transfer.

The aim of this study was to evaluate the influence of maternal age and oestradiol concentrations on blastocyst development and live birth rates in natural cycle IVF-embryo transfer. This observational study included 397 natural cycles with IVF embryo transfer for female infertility with embryo transfer on day 5. The cycles were divided into two groups according to the woman's age (<39 and > or = 39 years of age), and into two groups according to oestradiol concentrations on the day of human chorionic gonadotrophin (HCG) administration (0.4-0.49 nmol/l and 0.5-1.2 nmol/l). Comparison between the cycles in younger versus older age groups showed significant differences in blastocyst development rate, live birth rate per embryo transfer and live birth rate per cycle (55 versus 29%, 23 versus 3% and 13 versus 2% respectively) (P < 0.001). Comparison between cycles with lower versus higher oestradiol concentrations showed no significant differences in blastocyst development rate, live birth rate per embryo transfer and live birth rate per cycle (47 versus 49%, 18 versus 18%, and 11 versus 10% respectively). Advanced maternal age negatively predicts the success of natural cycle IVF, while low oestradiol concentrations on the day of HCG administration (ultrasound criteria fulfilled) do not negatively predict blastocyst development and success of natural cycle IVF.

Small uterine septum is an important risk variable for preterm birth.

OBJECTIVE(S): To evaluate whether a uterus with a small septum (arcuate uterus or class VI according to the American Fertility Society (AFS) classification) behaves similarly to a uterus with a larger septum (septate or subseptate uterus or AFS class V). STUDY DESIGN: Observational study included 826 singleton deliveries to 730 women with a history of hysteroscopic resection of the uterine septum. Data on deliveries were obtained from the National Perinatal Registry of Slovenia (NPIS). Multiple gestations were excluded. We analysed and compared perinatal outcomes before and after hysteroscopic resection in two groups of women: in women with a small uterine septum (Group A) and in those with a larger uterine septum (Group B). Data on the septum length were obtained during hysteroscopic resection by comparing the length of the 1.4-cm long yellow tip of the electric knife to the length of the resected septum. A small uterine septum was defined as having a length of 1.3-1.5 cm. RESULTS: The preterm birth rate in Group A (n=420) was 33.9% before and 7.2% after hysteroscopic resection (P<0.001); the preterm birth rate in Group B (n=406) was 36.5% before and 8.0% after hysteroscopic resection (P<0.001). The very preterm birth rate in Group A was 12.5% before and 3.1% after hysteroscopic resection (P<0.001); the very preterm birth rate in Group B was 15.0% before and 2.9% after hysteroscopic resection (P<0.001). After surgery, we registered a decreased need for neonatal intensive care, as well as a significant decrease in stillbirth and neonatal death rates in both groups of patients. CONCLUSION(S): Similarly to a large uterine septum, a small uterine septum or arcuate uterus is an important hysteroscopically preventable risk variable for preterm birth.

Blastocyst formation--good indicator of clinical results after ICSI with testicular spermatozoa.

BACKGROUND: The aim of this study was to evaluate the role of blastocyst culture in patients with azoospermia. METHODS: In 98 cycles embryos were cultured for 2 days and in 128 cycles for 5 days to reach the blastocyst stage; a maximum of two of the most developed embryos were transferred in each group. RESULTS: There was a negative correlation between a high (>/=20 IU/l) male serum FSH and embryo development, manifested as embryos not reaching the morula stage on day 5 (r = 0.387; P < 0.05). After prolonged culture, 23% of embryos reached the blastocyst stage. The pregnancy rates per transfer, and the abortion rates were approximately the same in the day 2 group and the day 5 group (20 versus 20% and 19 versus 18% respectively). After blastocyst transfer, a high clinical pregnancy rate (55%) and a low abortion rate (6%) were achieved, whereas the transfer of arrested embryos provided a low pregnancy rate (2%) and a high abortion rate (100%). If only blastocysts had been transferred on day 5, the clinical pregnancy rate per started cycle would have been approximately the same in both groups (13 versus 16%). CONCLUSIONS: Blastocyst formation is a good indicator of clinical results after ICSI with testicular sperm.

Infertility treatment by in vitro fertilization in patients with minimal or mild endometriosis.

PURPOSE: To estimate the clinical effectiveness of in vitro fertilization treatment in patients with minimal or mild endometriosis (stages I and II) in comparison to the patients with tubal infertility in terms of fertilization, pregnancy and livebirth rates. METHODS: Retrospective analysis of the outcome of IVF-ET in 612 cycles of the patients with endometriosis (389 stimulated with HMG/HCG and 223 co-treated with GnRH-a) and in 7,339 cycles of the patients with tubal infertility (5,520 stimulated with HMG/HCG and 1,819 co-treated with GnRH-a). RESULLTS: Regardless of the type of ovarian stimulation, the fertilization rate per treated cycle was practically the same in both groups (endometriosis 81.4% vs tubal infertility 84.2%; p = 0.07). However, in the endometriosis group the pregnancy rate was higher (25.3% vs 18.9%; p = 0.000), and so was the livebirth rate (19.0% vs 14.2%; p = 0.003). Considering the type of ovarian stimulation, the fertilization rate in the endometriosis group was almost the same in the HMG/HCG (81.2%) and in the GnRH-a co-treated cycles (81.6%), and did not differ from that in the tubal infertility group (83.6% in the HMG/HCG vs 85.9% in the GnRH-a cycles). In the GnRH-a co-treated cycles the pregnancy rate and the livebirth rate were not significantly higher in the endometriosis group than in the tubal infertility group (27% and 20.2% vs 22.2% and 17.5%). In the HMG/HCG stimulated cycles the pregnancy rate was significantly higher in the endometriosis than in the tubal infertility group (24.3% vs 17.7%; p = 0.004), and so was the livebirth rate (18.4% vs 13.0%; p = 0.008). CONCLUSION: In patients with minimal or mild endometriosis the IVF-ET procedure is at least as effective as in patients with tubal infertility.

Subpopulations of human granulosa-luteal cells obtained from gonadotropin- or gonadotropin-releasing hormone agonist/gonadotropin-treated follicles in in vitro fertilization-embryo transfer cycles.

PURPOSE: Our purpose was to find the differences in granulosa-luteal cells obtained from gonadotropin-versus gonadotropin-releasing hormone (GnRH) agonist/gonadotropin-treated follicles in in vitro fertilization-embryo transfer (IVF-ET) cycles. METHODS: Granulosa-luteal cells were obtained from 45 follicles of women undergoing IVF-ET with gonadotropin releasing hormone (GnRH) agonist and human menopausal gonadotropin (hMG) and from 45 follicles of women with hMG IVF-ET cycles. Subpopulations of granulosa-luteal cells were observed by computerized image analysis in which human chorionic gonadotropin (hCG) was localized using immunoperoxidase staining. RESULTS: The luteinized granulosa-luteal cells from hMG-treated follicles were larger than those from GnRH agonist/hMG-treated follicles. The hMG-treated follicles contained more hCG-stained cells, particularly those with cytoplasmic hCG localization. CONCLUSIONS: We found differences in morphometric characteristics and hCG localization in granulosa-luteal cells obtained from hMG-versus GnRH agonist/hMG-treated follicles. We presume that the results indicate the influence and importance of luteal-phase support on the clinical pregnancy rate in GnRH agonist/hMG-treated IVF-ET cycles.

Pretreatment evaluation of adnexal tumors predicting ovarian cancer.

Kobal B, Rakar S, Ribic-Pucelj M, Tomazevie T, Zaletel-Kragelj L. Pretreatment evaluation of adnexal tumors predicting ovarian cancer. The objective of this study was to determine the ability of tumor marker assessment, gray-scale transvaginal with color Doppler ultrasonography to predict ovarian malignancy. One hundred thirty-four subjects with ovarian masses who entered the study prospectively underwent pelvic examination, tumor marker assessment and gray-scale transvaginal with color flow Doppler ultrasonography preoperatively. Malignancy predictors were statistically evaluated with stepwise multiple logistic regression, and the scores from the model were transformed to probability for having a malignant disease. The presence of neovascularization, intracystic papillary projections, elevated serum CA 125, and age over 45 years were significant predictors for malignancy. Positive predictive value (PPV) for the regression model was 89.0%, and negative predictive value (NPV) was 96.8%. Probability for malignancy ranged from 0.004 to 0.991 depending on which covariates were included. Logistic regression analysis of pretreatment diagnostic gray-scale and color Doppler ultrasonographic characteristics, together with CA 125 enabled a creation of probability assessment scale for individual estimation of ovarian mass, which may contribute to final clinical decision.

Safe and effective fluid management by automated gravitation during hysteroscopy.

OBJECTIVE: The automated gravitational Vario Flow system with weighing-based electronic fluid deficit indicator was used in order to reduce the risk of fluid intravasation during continuous flow hysteroscopic procedures. Early experiences are reported. METHODS: Between August 1996 and July 1997, the Vario Flow with fluid deficit indicator and alarm system was used in 203 hysteroscopic operations. Between January 1994 and August 1996 the Vario Flow without fluid deficit indicator was used in 240 hysteroscopic operations. In all, there were 443 hysteroscopic operations: 301 metroplasties, 20 endometrial ablations, 10 cases of lysis of synechiae, 58 myomectomies and 54 polypectomies. The data on fluid deficit before and after the introduction of the electronic fluid deficit indicator were similar. RESULTS: Fluid deficit indicator was proved highly efficient in 203 operations. It provided the information on fluid deficit at any moment during hysteroscopic operations. Besides intrauterine pressure, the actual fluid deficit has become one of the leading parameters during our continuous flow hysteroscopic procedures. CONCLUSIONS: We therefore conclude that by using an automated gravitational system with fluid deficit indicator and alarm system, the safety for patients during hysteroscopic procedures has been increased.

Subpopulations of human granulosa-luteal cells obtained during early timed and during normally timed follicular aspiration in in-vitro fertilization-embryo transfer cycles.

OBJECTIVE: To find the differences between human granulosa-luteal cells obtained during early timed follicular aspiration to prevent severe ovarian hyperstimulation syndrome (OHSS) and during normally timed follicular aspiration. DESIGN: Retrospective analysis of clinical laboratory data. SETTING: In vitro fertilization unit, University Department of Obstetrics and Gynecology, Ljubljana, Slovenia. PATIENT(S): Twenty women undergoing IVF-ET at high risk for OHSS. INTERVENTION(S): Cells were obtained from the follicles of women who were stimulated with hMG and hCG during an early timed follicular aspiration of one ovary, 10-12 hours after hCG, and during a normally timed follicular aspiration of the contralateral ovary, 32-36 hours after hCG administration. MAIN OUTCOME MEASURE(S): Subpopulations of granulosa-luteal cells were observed by computerized image analysis in which hCG was localized using immunoperoxidase staining. RESULT(S): Early timed follicular aspirates contained no oocytes and only a scant number of granulosa cells. Granulosa-luteal cells were smaller than those from normally timed follicular aspirates. We identified three subpopulations in early timed follicular aspirates: nonluteinized, small luteinized, and medium luteinized cells. In normally timed follicular aspirates, four subpopulations were identified, including large luteinized cells. The normally timed follicular aspirates contained more hCG-stained cells. Three staining types of hCG localization were found: on the surface membrane, on the surface membrane and within the cytoplasm, and only within the cytoplasm of cells from normally timed follicular aspirates. Early timed follicular aspirates contained only cells with membrane hCG localization. CONCLUSION(S): We found differences in morphometric characteristics and hCG localization between human granulosa-luteal cells obtained during early timed follicular aspiration to prevent severe OHSS and during normally timed follicular aspiration.

Microsurgery and in-vitro fertilization and embryo transfer for infertility resulting from pathological proximal tubal blockage.

The aim of this study was to evaluate the prognosis for the patients after the treatment of infertility resulting from proximal tubal blockage using microsurgical tubocornual anastomosis and in-vitro fertilization (IVF) and embryo transfer complementarily. A total of 59 microsurgical operations (1986-1992) for infertility resulting from pathological proximal tubal lesions were analysed. The cumulative live birth rate was 52% for tubocornual anastomosis, 58% for bilateral operations and 28% for two-site operations. In all, 35 singleton babies were born. Of the 32 operated patients who did not deliver within 2 years of surgery, 21 were treated by 66 IVF cycles; 12 babies were born. The live birth rate was 18% per cycle and 57% per patient. Combining both treatment methods the cumulative live birth rate was improved up to 69% in the group of tubocornual anastomoses, up to 75% in the group of bilateral operations, and up to 57% in the group of two-site operations. Complementary use of microsurgery and IVF and embryo transfer improves the prognosis for selected infertile patients with pathological proximal tubal blockage. In the absence of pregnancy, IVF and embryo transfer should be commenced 1 year after surgery.

An automated gravitational system for delivery of low-viscosity media during continuous-flow hysteroscopy.

We constructed an automated gravitational system to control fluid dynamics during hysteroscopic operations. The new system allows linear regulation of intrauterine pressure by varying the flow by simply changing the height of the fluid-filled bag above the patient. The outflow from the automated gravitational system is also driven by gravity. Between January 1994 and June 1995 we performed 88 hysteroscopic operations: 10 myomectomies, 8 endometrial ablations, 3 polypectomies, 3 lysis of synechiae, and 64 transcervical metroplasties. With the Vario Flow system we obtained good visualization, and all operations were performed adequately in one attempt. No surgical or general complications were encountered. We presume that patient safety will be increased further with the second version of this system, which has a built-in electronic fluid deficit-control system.

Early timed follicular aspiration prevents severe ovarian hyperstimulation syndrome.

PURPOSE: Early timed follicular aspiration (ETFA) of one ovary 10-12 hr after administration of chorionic gonadotropin (hCG) is an attempt to prevent severe ovarian hyperstimulation syndrome (OHSS). After the introduction of early timed follicular aspiration ETFA of one ovary in IVF/ET cycles at high risk for severe OHSS, no cases of severe OHSS were registered in the Ljubljana IVF/ET program. In the period before preventive ETFA (1984-1992) there were 16 cases of severe OHSS of 4798 IVF/ET cycles followed by 577 clinical pregnancies. After the introduction of ETFA (1992-1993) there were no cases of severe OHSS of 2289 IVF/ET cycles followed by 364 clinical pregnancies. METHODS: We attempted to evaluate the significance of this observation by comparing two groups of female infertility IVF/ET cycles at high risk for severe OHSS. The occurrence of severe OHSS and clinical parameters in the two groups of IVF/ET cycles at high risk for severe OHSS were compared. RESULTS: In the group of 106 IVF/ET female infertility cycles at high risk of severe OHSS with preventive ETFA, there were no cases of severe OHSS. In the control group of 92 IVF/ET female infertility cycles at high risk for severe OHSS with normally timed follicular aspiration (NTFA) of both ovaries, severe OHSS occurred in 16 cases. The difference in the occurrence of severe OHSS between the two groups is highly significant (P < 0.005), both in hMG/hCG- and in GnRHa/hMG/hCG-induced IVF/ET cycles. No difference in live birth rate (16 vs. 16%) between the two groups was noted. CONCLUSIONS: Considering these results we conclude that ETFA is another successful option to decrease the incidence of severe OHSS in assisted reproduction. The preventive effect of follicular aspiration seems to depend on its timing.

Subpopulations of human granulosa-luteal cells in natural and stimulated in vitro fertilization-embryo transfer cycles.

OBJECTIVE: To find out the differences between human granulosa-luteal cells derived from natural and stimulated IVF-ET cycles. DESIGN: Cells were obtained from dominant follicles of 52 women with natural cycles in whom preovulatory hCG was given when the follicle was mature and from 50 dominant follicles of women undergoing IVF-ET with hMG and hCG. SETTING: In Vitro Fertilization Unit, University Department of Obstetrics and Gynecology Ljubljana, Slovenia. MAIN OUTCOME MEASURE: Four subpopulations of cells were observed by computerized image analysis in which hCG was localized using immunoperoxidase staining. RESULTS: The nonluteinized granulosa cells from natural cycles were larger than those from the stimulated ones. In luteinized cell types, there was no difference in cell area between natural and stimulated cycles. Three staining types of hCG localization were found: on the surface membrane, on the surface membrane and within the cytoplasm, and within the cytoplasm alone. The hCG stained cells from natural cycles were larger than the ones from stimulated cycles. The natural developing follicles contained more hCG stained cells than the stimulated ones. The follicles with fertilizable oocytes had more cells with cytoplasmic hCG localization. Only in natural cycles was there was a correlation between follicular fluid hCG levels and the percentage of the hCG stained cells. CONCLUSION: We found differences in morphometric characteristics and hCG localization between human granulosa and granulosa-luteal cells obtained from natural and stimulated IVF-ET cycles.

Risk factors for ectopic pregnancy after in vitro fertilization and embryo transfer.

PURPOSE: To find the incidence of ectopic pregnancy (EP) in patients who conceived in the IVF-ET program, and risk factors affecting the occurrence of EP. METHODS: We analyzed the effects of the indication for IVF, type of ovarian stimulation (hMG + hCG vs. GnRH + hMG + hCG), type of embryo transfer (transcervical intratubal, intrauterine in chest-knee position and intrauterine in lithotomy position) and number of embryos transferred on the occurrence of EP. EP was treated by laparotomy, prostaglandin E2 or laparoscopic surgery. RESULTS: In 7991 stimulated and 92 natural cycles treated in the Ljubljana IVF-ET program between May 1983 and June 1994 we achieved 1059 pregnancies, of which 44 were ectopic (incidence 4.1%), the main risk being tubal factor infertility. There were 38 (86.3%) tubal, 3 (6.8%) heterotopic, 1 (2.4%) ovarian, and 2 (4.5%) cornual EP. In two patients multiple tubal EP occurred (1 twin, 1 triplet). Forty-two patients (95.4%) had tubal factor infertility, 1 (2.3%) unexplained, and 1 (2.3%) patient had male factor. The incidence of EP in patients with tubal infertility was 5.4%, in patients with unexplained infertility 2.0% and in those with male factor 0.9%. There appeared to be no correlation between the two superovulatory methods. With transcervical intrauterine ET the incidence of EP was 0 of 5 clinical pregnancies (CP); with intrauterine in chest-knee position it was 26 (3.5%) of 738 CP; with intrauterine in lithotomy position it was 17 (5.4%) of 316 CP. The difference between the two types of intrauterine ET is not statistically significant. The incidence of EP did not correlate with the number of embryos transferred. The average initial values of beta hCG performed 17 days after ET were significantly lower in patients with EP than in those with normal singleton pregnancy (157 +/- 143 mIU/ml vs. 408 +/- 148 mIU/ml). CONCLUSIONS: EP can complicate the IVF procedure. The main risk factor is tubal infertility with or without previous tubal surgery. The low initial value of beta hCG has a strong predictive value in the diagnosis of EP.

Influence of follicular phase duration on human granulosa-luteal cell subpopulations in natural and stimulated IVF-ET cycles.

OBJECTIVES: To observe the granulosa-luteal cell subpopulations presented within follicular aspirates concerning duration of the follicular phase and the type of IVF protocol. DESIGN: Cells were obtained from dominant follicles of 40 women with natural IVF-ET cycles, in which preovulatory hCG was given when the follicle was mature, and from 40 follicles of 32 women with hMG and hCG stimulated IVF-ET cycles. Granulosa-luteal cell subpopulations were observed by computerized image analysis in which hCG was localized using immunoperoxidase staining. RESULTS: (1) The nonluteinized granulosa cells from natural developing follicles were larger than those from stimulated ones regardless of the follicular phase duration. (2) The size of each luteinized cell subpopulations was influenced neither by the two IVF protocols nor by the follicular phase duration. (3) The hCG stained cells from natural developing follicles were larger than the ones from stimulated follicles and their relative number in aspirates was higher. Cell areas and distribution were not influenced by the duration of follicular phase. (4) In stimulated conditions, hCG stained cells became larger if follicular phase was longer. CONCLUSIONS: Duration of the follicular phase influences the immunocytochemical hCG localization and the morphometric characteristics of granulosa-luteal cell subpopulations presented within natural developing follicles and stimulated ones.

Preventing severe ovarian hyperstimulation syndrome in an in vitro fertilization/embryo transfer program. Use of follicular aspiration after human chorionic gonadotropin administration.

In 3,972 human menopausal gonadotropin (hMG) and human chorionic gonadotropin (hCG)-stimulated menstrual cycles, severe ovarian hyperstimulation syndrome (SOHSS) developed in 10 patients (0.25%), while in 627 hMG-, hCG- and gonadotropin releasing hormone analog (GnRH-a)-stimulated cycles, 6 patients (0.95%) developed SOHSS. In cases of threatening SOHSS in the follicular phase (excessive estradiol values, multiple follicles), a preventive method was applied: follicular aspiration 12 hours after hCG administration and regular oocyte retrieval 36 hours after hCG (17 patients). The method of post-hCG aspiration in one ovary was effective, leading to the withdrawal of all signs of SOHSS within six days after the second aspiration. In hMG-stimulated, pretreated patients there were four deliveries of seven healthy infants (two singleton, one twin and one triplet), while one pregnancy in seven GnRH-a-stimulated and pretreated patients ended in a spontaneous abortion. Post-hCG aspiration is a quick, simple and effective method that prevents the development of SOHSS and permits pregnancy in the treated cycle. Although the pregnancy rate in patients who developed SOHSS was higher (100% per embryo transfer), one should also consider the high spontaneous abortion rate (33.3% for the hMG- and 50% for the GnRH-a/hMG-treated groups) and the fact that SOHSS is a life-threatening condition, demanding expensive, intensive care. According to our experience, post-hCG follicular aspiration is the treatment of choice in patients with signs of SOHSS.