GnRH agonist plus vaginal progesterone for luteal phase support in ICSI cycles: a randomized study.

In this prospective randomized study, the effect of daily gonadotrophin-releasing hormone agonist (GnRHa) in the luteal phase on IVF and intracytoplasmic sperm injection (ICSI) outcomes was assessed. Women (n = 446) were counselled for IVF-ICSI, and randomized on the day of embryo transfer to group 1 (daily 0.1 mg subcutaneous GnRHa until day of beta-HCG) (n = 224) and group 2 (stopped GnRHa on day of HCG injection) (n = 222). Both groups received daily vaginal progesterone suppositories. Primary outcome was clinical pregnancy rate. Secondary outcome was ongoing pregnancy rate beyond 20 weeks. Mean age, oestradiol on day of HCG, number of oocytes retrieved, number of embryos transferred, and clinical and ongoing pregnancy rates were 28.9 ± 4.5 years, 2401 ± 746 pg/mL; 13.5 ± 6.0 oocytes; 2.6 ± 0.6 embryos, and 36.2% and 30.4% consecutively in group 1 compared with 29.7 ± 4.7 years, 2483 ± 867 pg/mL, 13.7 ± 5.5 oocytes, 2.7 ± 0.6 embryos, 30.6% pregnancy rate, and 25.7% ongoing pregnancy rate in group 2. No significant difference was found between the groups. Subcutaneous GnRHa during the luteal phase of long GnRHa protocol cycles does not increase clinical or ongoing pregnancy rates after IVF-ICSI.

The use of vaginal natural progesterone for prevention of preterm birth in IVF/ICSI pregnancies.

The aim of this study was to evaluate the effect of vaginal natural progesterone on the prevention of preterm birth in IVF/intracytoplasmic sperm injection (ICSI) pregnancies. A single-centre prospective placebo-controlled randomized study was performed. A total of 313 IVF/ICSI pregnant patients were randomized into two groups for either treatment with daily 400 mg vaginal natural progesterone or placebo, starting from mid-trimester up to 37 weeks or delivery. Amongst the patients, there were 215 singleton and 91 twin pregnancies. There was no significant difference in risk of preterm birth among all patients (OR 0.672, 95% CI 0.42-1.0. There was a significantly lower preterm birth rate in singleton pregnancies in the natural progesterone arm (OR 0.53, 95% CI 0.28-0.97) and no significant difference between both arms in twin pregnancies (OR 0.735, 95% CI 0.36-2). In conclusion, the administration of 400 mg vaginal natural progesterone from mid trimester reduced the incidence of preterm birth in singleton, but not in twin, IVF/ICSI pregnancies.

Prospective randomized study for hydrotubation versus no hydrotubation before intrauterine insemination in unexplained infertility.

The purpose of the study was to investigate the value of hydrotubation before intrauterine insemination (IUI). In 228 patients with the diagnosis of unexplained infertility, ovarian stimulation was performed before IUI, using 100mg of clomiphine citrate for 5 days from day 3 of the cycle and one ampoule of human menopausal gonadotrophin for 5 days from day 6 of the cycle. Folliculometry and determination of LH concentration in urine were performed daily until LH became positive, then randomization for hydrotubation before IUI versus no hydrotubation was performed. Fifteen patients were cancelled from the study due to poor response or stimulation of three or more follicles. A total of 213 patients were randomized as follows: 103 patients undergoing hydrotubation using 50 ml of saline and 110 patients with no hydrotubation. IUI was performed the following day and ongoing pregnancy occurred in 13 patients (12.6%) in the hydrotubation group and nine patients (8.2%) in the non-hydrotubation group with no significant difference (OR 1.66; 95% CI 0.62-4.63). In conclusion, hydrotubation before IUI does not improve pregnancy rate.

Highly purified hMG achieves better pregnancy rates in IVF cycles but not ICSI cycles compared with recombinant FSH: a meta-analysis.

OBJECTIVE: Human menopausal gonadotropin (hMG) was demonstrated to be superior to recombinant FSH (rFSH) regarding clinical outcomes. It is not clear whether this change in the evidence was due to the introduction of highly purified (HP) hMG. DESIGN: Systematic review of properly randomised trials comparing HP-hMG vs. rFSH in women undergoing in vitro fertilisation (IVF) and/or intracytoplasmic sperm injection (ICSI). A meticulous search was performed using electronic databases and hand searches of the literature. RESULTS: Six trials (2371 participants) were included. Pooling of the trials demonstrated that the probability of clinical pregnancy following HP-hMG administration was higher than rFSH and reached borderline significance (odd ratio (O.R) = 1.21, 95% confidence interval (CI) = 1.00 to 1.45), but the ongoing pregnancy/live-birth rate was not statistically different between the two drugs, although it showed strong trends towards improvement with HP-hMG (O.R = 1.19, 95% CI = 0.98 to 1.44). Subgroup analysis comparing both drugs in IVF cycles demonstrated a statistically significant better ongoing pregnancy/live-birth rate in favour of HP-hMG (O.R = 1.31, 95% CI = 1.02 to 1.68). On the other hand, there was almost an equal ongoing pregnancy/live-birth rate in ICSI cycles (OR = 0.98, 95% CI = 0.7 to 1.36). CONCLUSIONS: HP-hMG should be preferred over rFSH in women undergoing assisted reproduction, especially if IVF is the intended method of fertilisation.

Ultrasound cervical measurement and prediction of spontaneous preterm birth in ICSI pregnancies: a prospective controlled study.

A prospective controlled study was performed in which transvaginal ultrasound measurement of cervical length was compared in 222 twin ICSI pregnancies, 122 singleton ICSI pregnancies and 51 spontaneous singleton pregnancies. Preterm birth was defined as

Prospective randomized study comparing luteal phase support for ICSI patients up to the first ultrasound compared with an additional three weeks.

BACKGROUND: There is a consensus that administration of progesterone to women after IVF for luteal phase support (LPS) is associated with a higher ongoing pregnancy rate. However there are few studies, including only one randomized study, which have examined the optimal duration of LPS. METHODS: A questionnaire concerning details of LPS was returned from 21 leading IVF centres. We then randomized 257 women, who were pregnant after ICSI on day of first ultrasound, into two groups: to continue LPS for three more weeks or to stop on the day of ultrasound. RESULTS: The duration of LPS in the questionnaire varied from the day of positive pregnancy test up to 12 weeks of pregnancy in different centres. In the randomized study, 132 patients in Group A continued LPS for 3 weeks after first ultrasound, whereas 125 patients in Group B stopped LPS on day of first ultrasound. After confirming pulsations, the miscarriage rate up to 20 weeks of gestation was 4.6% (6/132) in group A and 4.8% (6/125) in group B [odds ratios (OR) = 0.94; 95% confidence intervals (CI) = 0.3-3.1]. Bleeding episodes were 15.9% in Group A compared with 20.8% in group B (OR = 0.72; 95% CI = 0.38-1.36). CONCLUSIONS: There is no international consensus about the duration of LPS; our single-centre randomized trial did not support extending the LPS beyond the day of first ultrasound demonstrating echoes and pulsations. Trials registry number-ISRCTN: 88722916.

Efficacy and safety of human menopausal gonadotrophins versus recombinant FSH: a meta-analysis.

LH activity has been proposed to influence treatment response and outcome. In order to assess its clinical profile and efficacy, human menopausal gonadotrophin (HMG) was compared with recombinant FSH (r-FSH) in IVF/intracytoplasmic sperm injection (ICSI) cycles. Computerized and hand searches were conducted for relevant citations. Primary outcome measures were live-birth and OHSS rates. Secondary outcomes were clinical pregnancy, multiple pregnancy, miscarriage rates and cycle characteristics. The live-birth rate was significantly higher with HMG [odds ratio (OR) = 1.20, 95% CI = 1.01-1.42] versus r-FSH, but OHSS rates (OR = 1.21, 95% CI = 0.78-1.86) were not significantly different. As for the secondary outcomes, there was statistical significance with regard to the clinical pregnancy rate also in favour of the HMG group. Even so, there were significantly fewer treatment days, total dose and embryos produced in the r-FSH group compared with the HMG group. The other secondary outcomes were not different between the two groups. In conclusion, HMG has been demonstrated to be superior to r-FSH with regard to the clinical outcomes, with equivalent patient safety during assisted reproduction.

The impact of spermatozoa preincubation time and spontaneous acrosome reaction in intracytoplasmic sperm injection: a controlled randomized study.

OBJECTIVE: To determine the optimum time interval between semen processing and incubation before intracytoplasmic sperm injection (ICSI) and correlate it with the acrosomal reaction rate. DESIGN: Controlled randomized study. SETTING: The Egyptian IVF-ET Center. PATIENT(S): Couples with male factor infertility undergoing ICSI using ejaculated semen. INTERVENTION(S): The patients were prospectively randomized according to differences in sperm preincubation time before ICSI into 1-hour, 3-hour, and 5-hour groups. The status of the acrosome was studied using electron microscopy. MAIN OUTCOME MEASURE(S): The primary outcome measures were fertilization rate and acrosome reaction rate. Secondary outcome measures were the implantation and pregnancy rates. RESULT(S): The rate of acrosomally reacted spermatozoa was the highest (68.2%) after 5 hours of incubation and lowest (25.6%) after 1 hour of incubation. The difference was statistically significant. The fertilization rate was the highest (74%) using spermatozoa incubated for 3 hours as compared with 1 hour (70%) and 5 hours (67%), but the difference was not statistically significant. CONCLUSION(S): Acrosome reaction is time dependent; the optimum incubation time of spermatozoa before ICSI was 3 hours, which resulted in the highest fertilization rate.

A prospective randomized study comparing coasting with GnRH antagonist administration in patients at risk for severe OHSS.

This work evaluated possible advantages of gonadotrophin-releasing hormone (GnRH) antagonist administration as an alternative to coasting in prevention of severe ovarian hyperstimulation syndrome (OHSS) in women undergoing IVF/ intracytoplasmic sperm injection. A prospective randomized study comparing coasting (group A) (n = 96) and GnRH antagonist administration (group B) (n = 94) in patients at risk of OHSS was performed. The primary outcome measure was high quality embryos. The secondary outcome measures were days of intervention, number of oocytes, pregnancy rate, number of cryopreserved embryos and incidence of severe OHSS. There were significantly more high quality embryos (2.87 +/- 1.2 versus 2.21 +/- 1.1; P < 0.0001), and more oocytes (16.5 +/- 7.6 versus 14.06 +/- 5.2; P = 0.02), in group B as compared with group A. There were more days of coasting as compared with days of antagonist administration (2.82 +/- 0.97 versus 1.74 +/- 0.91; P < 0.0001). In conclusion, GnRH antagonist was superior to coasting in producing significantly more high quality embryos and more oocytes as well as reducing the time until HCG administration. There was no significant difference in pregnancy rate between the two groups. No OHSS developed in either group.

Among women undergoing embryo transfer, is the probability of pregnancy and live birth improved with ultrasound guidance over clinical touch alone? A systemic review and meta-analysis of prospective randomized trials.

OBJECTIVE: To investigate the theory that ultrasound guidance during ET improves clinical outcomes. DESIGN: Systematic review of prospective, randomized, controlled trials comparing ultrasound with clinical touch methods of embryo catheter guidance. SETTING: Infertility centers. PATIENT(S): 5,968 ET cycles in women. INTERVENTION(S): Embryo transfer with or without ultrasound guidance. MAIN OUTCOME MEASURE(S): Meticulous electronic (e.g., PubMed, EMBASE, CENTRAL) and hand searches were performed to locate trials. Primary outcome measures were the live-birth, ongoing pregnancy, and clinical pregnancy rates. Secondary outcome measures were the implantation, multiple pregnancies, and miscarriage rates. In addition, the incidences of ectopic pregnancies and difficult transfers were evaluated. RESULT(S): Twenty-five studies were retrieved, of which five were excluded. Meta-analysis of the remaining studies (5,968 ET cycles in women) was conducted by using the Mantel-Haenszel method (fixed-effect model). There was a significantly increased chance of a live birth (odds ratio [OR] = 1.78, 95% confidence interval [CI] = 1.19 to 2.67), ongoing pregnancy (OR = 1.51, 95% CI = 1.31 to 1.74), clinical pregnancy (OR = 1.50, 95% CI = 1.34 to 1.67), embryo implantation (OR = 1.35, 95% CI = 1.22 to 1.50), and easy transfer rates after ultrasound guidance (OR = 0.68, 95% CI = 0.58 to 0.81). There was no difference in multiple pregnancy, ectopic pregnancy, or miscarriage rates. CONCLUSION(S): Ultrasound-guided ET significantly increases the chance of live birth and ongoing and clinical pregnancy rates compared with the clinical touch method.

Sperm suspension is a highly ultrasonically visible material: a novel model to study uterine activity.

BACKGROUND: The aims of this study were to find an ultrasonically echogenic material to study the uterine activity, and to test whether closing the vaginal speculum on the cervix prevents the displacement of the injected material. METHODS: A concentrated sperm suspension was used as an ultrasonically visible material. Forty-five women undergoing intrauterine insemination were randomized into: open speculum group (n=23) and closed speculum group (n=22). Mimicking embryo transfer, 50 ul of concentrated sperm suspension was injected intrauterine while the vaginal speculum was open in 23 patients. In the other group, the two blades of the vaginal speculum were closed on the cervix, then 50 ul of concentrated sperm suspension was injected. The ultrasonically visible material was observed in the uterine cavity for 10 min during which the procedure was video-recorded. RESULTS: The injected sperm suspension was clearly visible in all cases. In the closed speculum group, the echogenic droplet remained in the upper uterine segment in 18 cases (82%) and moved towards the lower uterine segment in six cases (18%). In the open speculum group, the echogenic droplet remained in the upper uterine segment in only six cases (26%) and it moved towards the lower uterine segment and passed through the cervical canal in 17 cases (74%). CONCLUSIONS: For the first time in the medical literature, a concentrated sperm suspension was used as an ultrasonographically visible material to study uterine activity. Closing the portio-vaginalis of the cervix prevents the displacement of the injected material.

Intrauterine insemination catheters for assisted reproduction: a systematic review and meta-analysis.

BACKGROUND: Intrauterine insemination (IUI) is the oldest and most practised form of assisted reproduction worldwide. We systematically reviewed the literature so that we could evaluate the use of soft versus firm catheters in subfertile women undergoing IUI. METHODS: Extensive searches were conducted for full-text manuscripts, conference abstracts, ongoing and unpublished trials. Primary outcomes were clinical pregnancy (CPR) and ongoing pregnancy (OPR)/live birth rates (LBRs) per woman. Secondary outcomes were multiple pregnancy rate (MPR) per clinical pregnancy, difficulty cannulating the cervix, bleeding and patient discomfort. Meta-analysis was performed using the Peto-modified Mantel-Haenszel fixed-effect model. RESULTS: Seven randomized trials were identified, and four were excluded. No significant differences were noted for CPR and LBR per woman [OR = 0.96, 95% CI = 0.70-1.32 and OR = 0.82, 95% CI = 0.43-1.58, respectively]. As for the secondary outcomes, MPRs per cycle were also not significantly different. More difficulty was noted with soft catheters and more patient discomfort with firm catheters. Bleeding following the procedure was similar between the two groups. CONCLUSIONS: Catheter choice during IUI does not seem to be a detrimental factor for success, as in other assisted reproduction techniques (ART). More studies are warranted to draw definitive conclusions and support the results of this systematic review.

Screening for chromosomal abnormalities in 2650 infertile couples undergoing ICSI.

Chromosomal abnormalities are the major contributor to the genetic risks of infertility treatment associated with intracytoplasmic sperm injection (ICSI). The study objective was to assess prospectively the frequency of chromosomal aberrations in couples undergoing ICSI. A total of 2650 infertile couples (5300 patients) underwent chromosome analysis before undergoing ICSI in the Egyptian IVF-ET Centre. Heparinized blood samples were cultured, harvested and banded according to standard methods. Overall, 96.94% of the patients studied (5138/5300) had a normal karyotype, while the remaining 162 patients (3.06%) had an abnormal karyotype. Male patients constituted the majority of abnormalities; 138 males (85.19%) and 24 females (14.81%). These chromosomal aberrations included 117 cases (2.2%) of sex chromosome abnormalities; 113 males and four females. Forty-five patients (0.85%) had autosomal aberrations; 25 of them were males and 20 were females. The current data show that chromosomal abnormalities affect 3.06% of infertile patients, and occur in both sexes, but more predominantly in males undergoing ICSI for male factor infertility. It is recommended that chromosomal analysis be performed before undergoing ICSI, to identify patients who can be offered preimplantation genetic diagnosis.

HMG versus rFSH for ovulation induction in developing countries: a cost-effectiveness analysis based on the results of a recent meta-analysis.

Both cost and effectiveness should be considered conjointly to aid judgments about drug choice. Therefore, based on the results of a recent published meta-analysis, a Markov model was developed to conduct a cost-effectiveness analysis for estimation of the cost of an ongoing pregnancy in IVF/intracytoplasmic sperm injection (ICSI) cycles. In addition, Monte Carlo micro-simulation was used to examine the potential impact of assumptions and other uncertainties represented in the model. The results of the study reveal that the estimated average cost of an ongoing pregnancy is 13,946 Egyptian pounds (EGP), and 18,721 EGP for a human menopausal gonadotrophin (HMG) and rFSH cycle respectively. On performing a sensitivity analysis on cycle costs, it was demonstrated that the rFSH price should be 0.61 EGP/IU to be as cost-effective as HMG at the price of 0.64 EGP/IU (i.e. around 60% reduction in its current price). The difference in cost between HMG and rFSH in over 100,000 cycles would result in an additional 4565 ongoing pregnancies if HMG was used. Therefore, HMG was clearly more cost-effective than rFSH. The decision to adopt a more expensive, cost-ineffective treatment could result in a lower number of cycles of IVF/ICSI treatment undertaken, especially in the case of most developing countries.

Perinatal complications of assisted reproduction.

The main perinatal complications of assisted reproduction include congenital malformation, chromosomal aberrations, multiple pregnancy, and prematurity. Earlier studies and in vitro fertilization (IVF) registries showed that there was no increased incidence of congenital malformations in children conceived by IVF/intracytoplasmic sperm injection (ICSI). However, a large Australian study has found that by one year of age, the incidence of congenital malformations in IVF/ICSI children is increased in comparison with those naturally conceived. Several investigators found a slight but increased risk of chromosomal aberrations in ICSI children. Multiple pregnancy is a major cause of increased perinatal mortality due to increased incidence of both prematurity and congenital malformations. Even in singleton pregnancies conceived by assisted reproductive technologies, the risk of prematurity and newborns small for gestational age is increased. In this article, recently published work on perinatal complications associated with assisted reproductive technologies is reviewed.

Soft versus firm embryo transfer catheters for assisted reproduction: a systematic review and meta-analysis.

BACKGROUND: The true impact of the embryo transfer catheter choice on an IVF programme has not been fully examined. We therefore decided to systematically review the evidence provided in the literature so that we may evaluate a single variable in relation to a successful transfer, the firmness of the embryo transfer catheter. METHODS: An extensive computerized search was conducted for all relevant articles published as full text, or abstracts, and critically appraised. In addition, a hand search was undertaken to locate any further trials. RESULTS: A total of 23 randomized controlled trials (RCT) evaluating the types of embryo transfer catheters were identified. Only ten of these trials, including 4141 embryo transfers, compared soft versus firm embryo catheters. Pooling of the results demonstrated a statistically significantly increased chance of clinical pregnancy following embryo transfer using the soft (643/2109) versus firm (488/2032) catheters [P = 0.01; odds ratio (OR) = 1.39, 95% confidence interval (CI) = 1.08-1.79]. When only the truly RCT were analysed, the results were again still in favour of using the soft embryo transfer catheters [soft (432/1403) versus firm (330/1402)], but with a greater significance (P < 0.00001; OR = 1.49, 95% CI = 1.26-1.77). CONCLUSION: Using soft embryo transfer catheters for embryo transfer results in a significantly higher pregnancy rate as compared to firm catheters.