Time-limited hydrotubation combined with clomiphene citrate treatment for unexplained infertility.

PURPOSE: To evaluate time-limited hydrotubation combined with clomiphene citrate as treatment for unexplained infertility. MATERIALS AND METHODS: In this unblinded, randomized controlled trial of patients who had unexplained infertility, 40 patients were treated with time-limited hydrotubation (saline, 20 ml; flushed within 20 to 30 seconds) and clomphene citrate (total, 70 cycles) and 40 patients were treated with clomiphene citrate alone (total, 74 cycles). All women underwent an ovulation induction protocol with clomiphene citrate (100 mg/d orally for five days, from day 3 to day 7 of the cycle). Hydrotubation was performed after detection of the dominant follicle. RESULTS: There were 15 pregnancies in the 80 patients (19%) (total, 144 stimulated cycles; 10% pregnancies per cycle). The frequency of clinical pregnancy per cycle was significantly greater in patients who were treated with hydrotubation and clomiphene citrate (nine pregnancies per cycle [13%]) than those treated with clomiphene citrate alone (two pregnancies per cycle [3%]; odds ratio, 5.3; 95% confidence interval, 1.1 to 25.5; p ≤ 0.05). The frequency of pregnancy per patient (total, clinical, or chemical) was similar for the two treatment groups. The frequency of live birth or abortion per cycle or patient was similar between the two treatment groups. CONCLUSION: Time-limited hydrotubation and clomiphene citrate may increase the frequency of clinical pregnancy per cycle in women who have unexplained infertility.

The association between inherited thrombophilia and recurrent pregnancy loss in Turkish women.

OBJECTIVE: To investigate the relation between recurrent pregnancy loss (RPL) and factor V Leiden, prothrombin G20210A, and C677T methylenetetrahydrofolate reductase (MTHFR) mutations. MATERIALS AND METHODS: A case-control study was conducted on 95 consecutive cases with RPL, and 40 age-matched controls who had no history of pregnancy loss and had at least one successful pregnancy. After application of exclusion criteria, 60 patients in the study group and 40 control cases were compared for thrombophilic factors. RESULTS: Thirteen out of 60 RPL cases and one out of 40 in the control group were carriers of factor V Leiden mutation. While six patients were carriers of prothrombin G20210A gene mutation, none in the control group carried this mutation. Twenty-nine out of 60 RPL cases and 17 out of 40 control cases had MTHFR mutation. CONCLUSION: The authors found a positive correlation between RPL and FVL and FII gene mutations, but no significant association between RPL and MTHFR gene mutation.

Factors affecting pregnancy in IVF: age and duration of embryo transfer.

The aim of this retrospective study was to investigate factors affecting clinical pregnancy rates, especially age and duration of embryo transfer, in IVF/intracytoplasmic sperm injection cycles (1313 embryo transfers). Overall clinical pregnancy rate was 30.0% (n=394). Clinical pregnancy rates were found to be 31.6% for the <44 s interval, 25.9% for the 45-59 s interval and 23.6% for the > or = 60 s interval (P=0.020). In the <35 year age group, clinical pregnancy rates were 35.1%, 29.9% and 30.6%, and in the > or = 35 year age group, they were 26.9%, 21.0% and 13.4% (P=0.013), respectively. According to logistic regression analyses, the odds of failed pregnancy increased by 1.61 times [95% confidence interval (CI) 1.07-2.41] for embryo transfer durations longer than 60 s and odds ratios of a failed pregnancy were 1.53 (95% CI 1.18-1.99) in the > or = 35 year age group, 1.49 (95% CI 1.05-2.12) for fewer than five oocytes and 3.38 (95% CI 2.10-5.43) for fewer than two transferred embryos. In conclusion, to increase the likelihood of a successful pregnancy in women over 35 years of age, the duration of embryo transfer must be kept below 60 s. The number of oocytes obtained and the number of transferred embryos also play a role in the success of pregnancy.

A rare case of ileal embedding by an intrauterine device.

Ileal penetration by a copper-bearing intrauterine device (IUD) is a rare but serious potential complication. This paper reports the case of a 30-year-old gravida 4 para 3 woman with ileal embedding by an IUD. Laparoscopy was performed on the patient 4 months after the insertion of the IUD. When the tail of the IUD was seen during laparoscopy protruding outside the small bowel, the device was removed through a 1-cm incision in the ileum by laparotomy. This report demonstrates a rare case of ileal embedding of an IUD.

Effect of PGD on implantation and ongoing pregnancy rates in cases with predominantly macrocephalic spermatozoa.

Although its occurrence is rare, the presence of large headed or macrocephalic spermatozoa and increased chromosomal abnormality has recently been reported by several groups. Moreover, when intracytoplasmic sperm injection (ICSI) was performed with samples containing macrocephalic spermatozoa, lower fertilization and implantation rates result in poor clinical outcome. In order to evaluate the impact of preimplantation genetic diagnosis (PGD) on implantation and ongoing pregnancy rates in these couples, the results of 23 PGD cycles were compared with non-PGD cycles (n = 60) as well as cycles with absolute teratozoospermia (having zero normal morphology) with (n = 14) or without PGD (n = 66). Out of 82 embryos biopsied in the macrocephalic sperm group, abnormalities were detected in 46.4% of the embryos analysed. Most of the abnormalities were trisomies (37.0%) and complex aneuploidies (51.9%). A 33.3% pregnancy rate was achieved by selectively transferring euploid embryos after PGD with the statistically higher implantation rate of 25.0% compared with non-PGD cycles (IR: 12.3%, P < 0.01). Moreover, only one missed abortion (14.3%) was observed in the PGD group, whereas seven of the 15 pregnancies resulted in abortion in the non-PGD group (46.7%). Preliminary results indicate that patients should be counselled for increased chromosomal abnormality and a possible beneficial effect of eliminating chromosomally abnormal embryos with PGD on a bortion rates.

Assessment of DNA fragmentation and aneuploidy on poor quality human embryos.

In human assisted reproduction, low embryo quality due to retarded growth and abnormal cellular morphology results in fewer embryos suitable for transfer. This study aimed to assess the extent of DNA fragmentation and aneuploidy in spare slow growing or arrested human embryos. In 19 assisted reproduction cycles, a total of 57 embryos unsuitable for embryo transfer were used for simultaneous apoptosis and aneuploidy assessment. Among them, 31 (54.3%) showed DNA fragmentation by terminal deoxynucleotidyl transferase-mediated dUDP nick-end labelling (TUNEL) analysis. Among 26 embryos that were negative for TUNEL, interpretable fluorescence in-situ hybridization (FISH) results were obtained for 25 embryos (96.2%). Sixteen embryos were detected to be chromosomally abnormal (64.0%); three were found to be chaotic, six had complex aneuploidy, six had complete monosomy and one was polyploid. The results show that a high level of DNA fragmentation and aneuploidy are common in embryos with slow growth and/or low quality. More detailed studies are needed to assess the effect of factors such as ovarian stimulation regimens and in-vitro culture conditions. Moreover, application of simultaneous TUNEL and FISH techniques can be informative regarding DNA integrity and aneuploidy.

Serum levels of insulin, IGF-1, and IGFBP-1 in pre-eclampsia and eclampsia.

OBJECTIVES: To investigate whether the serum concentrations of insulin, insulin-like growth factor-1 (IGF-1), and insulin-like growth factor binding protein-1 (IGFBP-1) were altered in women with mild pre-eclampsia, severe pre-eclampsia, and eclampsia. METHODS: In this prospective study, we investigated 20 mild pre-eclamptic, 20 severe pre-eclamptic, and 20 eclamptic patients in the third trimester. The control group consisted of 20 healthy pregnant women. Serum levels of insulin, IGF-1, and IGFBP-1 were measured. RESULTS: In patients with eclampsia, serum levels of IGF-1 were lower, and IGFBP-1 were higher, respectively, than control and other study groups (P<0.001) The values of IGF-1 in mild pre-eclampsia and severe pre-eclampsia were lower compared with control groups (both P<0.01), but there were no differences between mild and severe pre-eclampsia. The serum levels of IGFBP-1 in severe pre-eclampsia were higher compared with control groups (P<0.01), but there was no statistical difference between mild pre-eclampsia and other groups. CONCLUSIONS: IGF-1 was lower, and IGFBP-1 was higher in pre-eclamptic and eclamptic patients than controls, these alterations were related to the severity of pre-eclampsia.

Embryo development characteristics in Robertsonian and reciprocal translocations: a comparison of results with non-translocation cases.

The effect of translocations on embryo development was evaluated and results were compared in terms of embryo development with those of embryos obtained from standard intracytoplasmic sperm injection (ICSI) cycles. In 23 translocation carriers with 34 cycles, fertilization, pronuclear morphology scoring (PMS), developmental arrest, cleavage and blastocyst formation were evaluated and compared with embryos obtained from non-translocation cases undergoing ICSI (n = 98 cycles). In 28 cycles, preimplantation genetic diagnosis (PGD) was performed on prezygotes (first and second polar body biopsy for female carriers; n = 3) or on embryos having seven or more blastomeres (blastomere biopsy; n = 25). In six cycles for four couples, probes for translocated chromosomes were not available, so PGD could not be performed. Overall, in translocation cases, a lower fertilization rate, a higher rate of retarded embryo development, and a lower rate of blastocyst formation were observed compared with embryos of non-translocation cases. Fluorescence in-situ hybridization (FISH) analysis showed a 70.9% abnormality rate for reciprocal translocations and 55.0% for Robertsonian translocations respectively. In cases with Robertsonian and reciprocal translocation carriers, the probability of poor embryo development, which may be a result of high segregation abnormalities, may negatively affect the outcome of assisted reproductive techniques. This poor prognosis should also be considered when genetic counselling for translocation is given.

Pronuclear morphology scoring and chromosomal status of embryos in severe male infertility.

BACKGROUND: The study aim was to evaluate the relationship between pronuclei morphology scoring (PNMS) and the chromosomal complement of embryos in couples with severe male infertility undergoing ICSI. A total of 3116 pre-embryos was scored according to PNMS in 452 cycles. METHODS: Pre-embryos were classified into eight categories based on the alignment, size, linear or irregular distribution of pronuclear bodies (PNB), position and clarity of cytoplasmic halo and abutting of the pronucleus. These categories were subdivided into groups I and II according to the similarity and distribution of PNB. RESULTS: In total, 2574 pre-embryos formed by using ejaculated sperm, while 542 pre-embryos developed by injection of testicular sperm or round spermatids. More group II pre-embryos with markedly different morphology from group I were formed after ICSI with testicular sperm than with fresh ejaculated sperm (32.1 versus 22.7%, P < 0.01). Of 490 pre-embryos in which pronuclear morphology was evaluated, 263 were biopsied for preimplantation genetic diagnosis. The rate of chromosomal abnormality was higher in embryos developed from group II pre-embryos (52.2%) than in embryos developed from group I prezygotes (37.6%, P < 0.05). CONCLUSIONS: Group II pre-embryos had markedly different morphology from group I, and had a low rate of blastocyst formation and high risk of chromosomally abnormal embryos. When testicular sperm and round spermatids were used for ICSI, more group II pre-embryos and chromosomally abnormal embryos were produced than with ejaculated sperm. Pronuclear morphology was correlated with chromosomal complement, and impacted upon by the sperm source.

Measurement of plasma glutathione S-transferase in hepatocellular damage in pre-eclampsia.

Glutathione S-transferase (GST) is a cytosolic enzyme found in high concentrations in the liver. We investigated the value of plasma GST measurements in pre-eclamptic patients. A total of 80 patients (40 in the pre-eclampsia group and 40 in the control group) were recruited. All patients were evaluated for GST, alanine aminotransferase (ALT), aspartate aminotransferase and lactate dehydrogenase. Pre-eclampsia was defined as the occurrence, after 20 weeks' gestation, of a diastolic blood pressure greater than 90 mmHg on two or more occasions at least 4 h apart, and concomitant proteinuria greater than 0.3 g/l over a 24-h urine collection period. There was no statistical difference between the pre-eclampsia and control groups in terms of ALT, gestational age, maternal age or number of previous pregnancies; a significant difference was found between the pre-eclampsia and control groups in terms of GST. Preeclampsia represents a significant cause of maternal and perinatal morbidity and mortality. Accurate assessment of hepatocellular damage is essential in the clinical management of these patients. GST levels in pre-eclamptic patients were found to be much higher (131.98 IU/l) than in control patients (68.67 IU/l), and this high level suggests hepatocellular damage. We concluded that measurement of plasma GST might provide an earlier and much more sensitive indicator of hepatocellular damage than other liver-function tests.

Correlation of P-selectin and lipoprotein(a), and other lipid parameters in preeclampsia.

Preeclampsia is a pregnancy specific disorder and is thought to be associated with generalized endothelial dysfunction. P-selectin, an adhesion molecule, mediates the interaction of monocytes, platelets, and endothelial cells. Increased P-selectin levels and altered lipid and lipoprotein metabolism were reported in preeclampsia and during pregnancy. In order to investigate the relationship between serum P-selectin and lipoprotein(a), and other lipid parameters, 28 preeclampsia [13 severe (group I) and 15 mild preeclampsia (group II), 15 healthy pregnant (group III) and 20 non-pregnant (group IV)] women were investigated. Serum P-selectin, lipoprotein(a), total cholesterol, triglyceride, and high density lipoprotein cholesterol were measured and low-density lipoprotein cholesterol was derived. Serum P-selectin concentrations were consistently and significantly higher in the severe preeclampsia group than in the mild preeclampsia, healthy pregnancy, and non-pregnant control groups (P<0.0001, for all). The mild preeclampsia group also had increased serum P-selectin concentrations compared with the healthy pregnancy group and non-pregnant controls (P<0.05 and P<0.0001, respectively). Serum P-selectin and lipoprotein(a) levels revealed a significant and linear increase with the severity of preeclampsia. There were also significant (in groups I and II) and borderline (in groups III and IV) correlations between P-selectin and total cholesterol. The present study suggests that P-selectin may be an additional risk marker for preeclampsia, and may be useful in distinguishing women with mild and severe preeclampsia and normal pregnancy.

Changes in leukocyte, granulocyte and lymphocyte counts following antenatal betamethasone administration to pregnant women.

OBJECTIVE: Preterm labor and premature rupture of membranes are associated with a mild leukocytosis. However, we have observed a higher maternal leukocyte count after antenatal betamethasone therapy. We planned this study to evaluate the effects of antenatal betamethasone treatment on maternal leukocyte, granulocyte and lymphocyte count. METHODS: Forty-six pregnant women with the diagnosis of preterm labor between 28 and 33 weeks of gestation age received 12 mg betamethasone at a 12-h interval. The control group consisted of 50 pregnant women between 28 and 33 weeks of gestational age with no medical or obstetrics problems. After a baseline venous sampling, serial leukocyte, granulocyte and lymphocyte counts were obtained every 6 h until it returned to baseline value. RESULTS: There were no statistically significant differences in the control group with respect to the total leukocyte, lymphocyte, and neutrophil count. Total leukocyte and granulocyte counts were increased by 29.8% and 17.8% within 24 and 12 h after betamethasone injection, respectively (P < 0.01). A significant reduction in lymphocyte count was observed within 12 h (45.4%) after betamethasone injection (P < 0.01). All changes in leukocyte, granulocyte and lymphocyte counts returned to baseline values within 3 days. CONCLUSION: Antenatal betamethasone therapy leads to an increase in maternal leukocyte count and a decrease in lymphocyte count. This effect is transient and any leukocytosis persisting for more than 3 days is not due to betamethasone administration.

Comparison of labor induction with misoprostol vs. oxytocin/prostaglandin E2 in term pregnancy.

OBJECTIVE: To compare the efficacy and safety of intravaginal and oral misoprostol vs. oxytocin/prostaglandin E2 (PGE2) gel for third trimester labor induction. METHODS: Two hundred twenty-four pregnant women were randomized to induction of labor either with misoprostol or oxytocin and PGE2 gel. Patients in the misoprostol group (n = 112) received 100 micrograms intravaginal misoprostol followed by 100 micrograms p.o. every 2 h. The oxytocin/PGE2 group consisted of 112 patients who underwent PGE2 cervical instillation 6 h before continuous oxytocin infusion. The perinatal, intrapartum and neonatal characteristics of both groups were determined. RESULTS: Induction to active phase of labor was successfully achieved in 96 women (85.7%) in the misoprostol group vs. 86 women (76.8%) in the oxytocin/PGE2 group, but the drug initiation-delivery interval was significantly shorter in the misoprostol group (9.2 +/- 2.4 h) than in the oxytocin/PGE2 group (15.2 +/- 3.2 h, P < 0.001). The incidence of adverse intrapartum outcomes was similar for both methods. Intravaginal misoprostol 100 micrograms followed by a single oral dose of 100 micrograms misoprostol safely produced labor and a vaginal delivery in 70% of patients. More than three tablets were required in only 10% of patients. There was a higher prevalence of cesarean section for failed induction in the oxytocin/PGE2 group than in the misoprostol group (13.4 vs. 6.3%, P < 0.001). The neonatal outcomes of both groups were also similar. CONCLUSION: Misoprostol is significantly more effective for labor induction than oxytocin/PGE2 gel. The maternal intrapartum and neonatal outcomes were the same for both induction regimens. From a clinical and perinatal perspective, misoprostol is an acceptable choice for labor induction.