Effectiveness of progestogens to improve perinatal outcome in twin pregnancies: an individual participant data meta-analysis.

BACKGROUND: In twin pregnancies, the rates of adverse perinatal outcome and subsequent long-term morbidity are substantial, and mainly result from preterm birth (PTB). OBJECTIVES: To assess the effectiveness of progestogen treatment in the prevention of neonatal morbidity or PTB in twin pregnancies using individual participant data meta-analysis (IPDMA). SEARCH STRATEGY: We searched international scientific databases, trial registration websites, and references of identified articles. SELECTION CRITERIA: Randomised clinical trials (RCTs) of 17-hydroxyprogesterone caproate (17Pc) or vaginally administered natural progesterone, compared with placebo or no treatment. DATA COLLECTION AND ANALYSIS: Investigators of identified RCTs were asked to share their IPD. The primary outcome was a composite of perinatal mortality and severe neonatal morbidity. Prespecified subgroup analyses were performed for chorionicity, cervical length, and prior spontaneous PTB. MAIN RESULTS: Thirteen trials included 3768 women and their 7536 babies. Neither 17Pc nor vaginal progesterone reduced the incidence of adverse perinatal outcome (17Pc relative risk, RR 1.1; 95% confidence interval, 95% CI 0.97-1.4, vaginal progesterone RR 0.97; 95% CI 0.77-1.2). In a subgroup of women with a cervical length of ≤25 mm, vaginal progesterone reduced adverse perinatal outcome when cervical length was measured at randomisation (15/56 versus 22/60; RR 0.57; 95% CI 0.47-0.70) or before 24 weeks of gestation (14/52 versus 21/56; RR 0.56; 95% CI 0.42-0.75). AUTHOR'S CONCLUSIONS: In unselected women with an uncomplicated twin gestation, treatment with progestogens (intramuscular 17Pc or vaginal natural progesterone) does not improve perinatal outcome. Vaginal progesterone may be effective in the reduction of adverse perinatal outcome in women with a cervical length of ≤25 mm; however, further research is warranted to confirm this finding.

Evaluation of offline analysis of archived three-dimensional volume datasets in the diagnosis of fetal brain abnormalities.

OBJECTIVE: To retrospectively evaluate the reliability of offline manipulation of archived three-dimensional (3D) ultrasound volumes in the assessment of the normal fetal brain and the diagnosis of fetal brain abnormalities. METHODS: Seventy-nine 3D volume datasets, archived at the time of scanning, from women attending a tertiary center, were analyzed. They comprised 52 cases with brain abnormalities and 27 normal controls. Postnatal magnetic resonance imaging or postmortem examination confirmed the final diagnosis in all cases with brain anomalies. Offline analysis of the 79 anonymized 3D volume datasets was carried out by three fetal medicine experts, examiner one (E1), examiner two (E2) and examiner three (E3), using 4D View software. The experts were blinded to any prior diagnosis or history. Data were collected on a specially designed data sheet and entered into a specialized database for analysis. Results were compared between examiners, with the initial two-dimensional (2D) diagnosis and with the final definitive diagnosis by calculation of percentage agreement and kappa coefficients. RESULTS: Of the 52 cases with brain anomalies, the correct diagnosis was reached in 88.5% (46/52), 98.1% (51/52) and 92.3% (48/52) of cases on analysis of the 3D volumes by E1, E2 and E3, respectively, whereas only 82.7% (43/52) of cases were correctly diagnosed on the initial 2D examination when compared with the definitive diagnosis. Fetuses without brain anomalies were identified as such by the three experts with 100% agreement. There was good agreement between the initial 2D examination and the analysis of 3D volumes by each of the experts: 86.1% for E1 (κ = 0.7), 89.9% for E2 (κ = 0.79) and 88.6% for E3 (κ = 0.76). CONCLUSIONS: 3D volume datasets are an appropriate and reliable format for storing data from examination of the fetal brain. Offline analysis of 3D datasets is a reliable method that can be used to help in the assessment of brain anomalies and could be a useful adjunct to realtime 2D ultrasonography.

13-14-week fetal anatomy scan: a 5-year prospective study.

OBJECTIVES: To assess the potential value of an early (first-trimester) ultrasound examination in depicting fetal anomalies by transabdominal (TAS) and transvaginal (TVS) sonography, to compare it with the traditional mid-trimester anomaly ultrasound examination and to evaluate the degree of patient acceptance of early sonography by the transvaginal route. METHODS: In this prospective study over a 5-year period (January 2002 to January 2007) 2876 pregnant women underwent a 13-14-week ultrasound examination. The scan was performed by TAS at first and then, if a full fetal anatomical survey was not achieved, by TVS. A mid-trimester fetal anatomy scan was then performed in patients who had not dropped out, miscarried or undergone pregnancy termination (n = 2834). RESULTS: In the early scan, analyzable data for 2876 TAS and 1357 TVS examinations showed that TVS was significantly better in visualizing the cranium, spine, stomach, kidneys, bladder and upper and lower limbs (P < 0.001). Complete fetal anatomical surveys were achieved by TAS in 64% of cases versus 82% of the cases in which it was attempted by TVS (P < 0.001). Patient body mass index significantly affected the ability of the sonographer to achieve a complete anatomical survey by both TAS and TVS (P < 0.001 and P = 0.004, respectively). The duration of the scan was significantly longer using TVS. The heart and kidneys were not properly visualized in 42% and 27% of cases, respectively, at the 13-week scan compared with 1.6% and 0% at the mid-trimester scan. The total number of cases in which anomalies were detected was 31. At the first-trimester scan, anomalies were detected in 21 fetuses and in 14 of these cases the parents chose pregnancy termination. At the second-trimester scan, anomalies were detected in 17 fetuses: 10 new anomalous cases along with seven cases already detected in the first-trimester scan. CONCLUSION: Besides its importance in screening for chromosomal abnormalities, the early scan has great potential in visualizing with precision fetal anatomy. TVS can be used to compliment difficult TAS examinations; however, patients do not always agree to undergo TVS. The mid-trimester scan remains crucial for detailed fetal anatomical survey.

In vitro fertilisation versus tubal reanastomosis (sterilisation reversal) for subfertility after tubal sterilisation.

BACKGROUND: Tubal sterilisation is the most popular contraceptive method in the world. Approximately 138 million women of reproductive age have had tubal sterilisation and there is evidence that increasingly younger women are being sterilized. With such large numbers of women choosing this option of birth control, it is clear that even if a small percentage of women later regret the decision, large numbers of women will seek counselling regarding reversal from their physicians. OBJECTIVES: To compare the efficacy of surgical tubal reanastomosis and in vitro fertilisation in terms of live birth rates. The morbidity and cost-effectiveness of both techniques were also to be compared. SEARCH STRATEGY: The following databases were searched: Cochrane Menstrual Disorders and Subfertility Review Group Specialised Register, MEDLINE (1966 to 2005), EMBASE (1980 to 2005), and other electronic databases. We handsearched the reference lists of trials, reviews and relevant textbooks; searched abstracts from relevant conferences, and personally communicated with experts in the field. SELECTION CRITERIA: Randomised and quasi-randomised trials comparing surgical reversal of tubal sterilisation with in vitro fertilisation (IVF). The method of allocation will be assessed and results subgrouped according to whether the trials were randomised or quasi-randomised. DATA COLLECTION AND ANALYSIS: No trials were found that met the selection criteria. MAIN RESULTS: No data exist on which to report. AUTHORS' CONCLUSIONS: There is a need for well-designed controlled clinical trials to compare the efficacy and safety of surgical reversal of tubal sterilisation and IVF in restoring fertility in women seeking pregnancy following tubal sterilisation.

Gonadotrophin-releasing hormone antagonists for assisted conception.

BACKGROUND: Gonadotrophin-releasing hormone antagonists produce immediate suppression of gonadotrophin secretion, hence, they can be given after starting gonadotrophin administration. This has resulted in dramatic reduction in the duration of treatment cycle. Two different regimes have been described. The multiple-dose protocol involves the administration of 0.25 mg cetrorelix (or ganirelix) daily from day six to seven of stimulation, or when the leading follicle is 14 to15 mm, until human chorionic gonadotrophin (HCG) administration and the single-dose protocol involves the single administration of 3 mg cetrorelix on day seven to eight of stimulation. Assuming comparable clinical outcome, these benefits would justify a change from the standard long protocol of GnRH agonists to the new GnRH antagonist regimens. OBJECTIVES: To evaluate the evidence regarding the efficacy of gonadotrophin-releasing hormone (GnRH) antagonists with the standard long protocol of GnRH agonists for controlled ovarian hyperstimulation in assisted conception. SEARCH STRATEGY: We searched Cochrane Menstrual Disorders and Subfertility Group's Specialised Register, MEDLINE and EMBASE databases from 1987 to February 2006, and handsearched bibliographies of relevant publications and reviews, and abstracts of scientific meetings. We also contacted manufacturers in the field. SELECTION CRITERIA: Randomized controlled studies comparing different protocols of GnRH antagonists with GnRH agonists in assisted conception cycles were included in this review. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality and extracted data. If relevant data were missing or unclear, the authors have been consulted MAIN RESULTS: Twenty seven RCTs comparing the GnRH antagonist to the long protocol of GnRH agonist fulfilled the inclusion criteria. Clinical pregnancy rate was significantly lower in the antagonist group. (OR = 0.84, 95% CI = 0.72 - 0.97). The ongoing pregnancy/ live-birth rate showed the same significant lower pregnancy in the antagonist group (P = 0.03; OR 0.82, 95% CI 0.69 to 0.98).However, there was statistically significant reduction in incidence of severe OHSS with antagonist protocol. The relative risk ratio was (P = 0.01; RR 0.61, 95% CI 0.42 to 0.89). In addition, interventions to prevent OHSS (e.g. coasting, cycle cancellation) were administered more frequently in the agonist group (P = 0.03; OR 0.44, 95% CI 0.21 to 0.93). AUTHORS' CONCLUSIONS: GnRH antagonist protocol is a short and simple protocol with good clinical outcome with significant reduction in incidence of severe ovarian hyperstimulation syndrome and amount of gonadotrophins but the lower pregnancy rate compared to the GnRH agonist long protocol necessitates counseling subfertile couples before recommending change from GnRH agonist to antagonist..

Recombinant versus urinary human chorionic gonadotrophin for ovulation induction in assisted conception.

BACKGROUND: For the last few decades urinary human chorionic gonadotrophin has been used to induce final follicular maturation and for triggering ovulation in assisted conception. Recombinant technology has allowed the production of two drugs that can be used for the same purpose: to mimic the endogenous luteinizing hormone (LH) surge. This would allow commercial production to be adjusted according to market requirements. In addition all urinary contaminants would also be removed. Hence, this would allow the safe subcutaneous administration of a compound with less batch-to-batch variation. However, prior to a change in practice, the effectiveness of the recombinant drugs should be known, compared to the currently used urinary human chorionic gonadotrophins. OBJECTIVES: To assess the safety and efficacy of subcutaneous rhCG and high dose rLH compared with intramuscular uhCG for inducing final oocyte maturation and triggering ovulation. SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders and Subfertility Group trials register (27 August 2003), the Cochrane Central Register of Controlled Trials (CENTRAL on The Cochrane Library, issue 4, 2003), MEDLINE (1966 to Feb 2004) and EMBASE (1980 to Feb 2004). Searches were not limited by language. The bibliographies of included, excluded trials and abstracts of major meetings were searched for additional trials. Authors and pharmaceutical companies were contacted for missing and unpublished data. SELECTION CRITERIA: Two reviewers independently scanned titles and abstracts, and selected those that appeared relevant for collection of the full paper. Only truly randomised controlled trials comparing rhCG or high dose r-LH with urinary hCG for triggering ovulation in assisted conception for treatment of infertility in normogonadotrophic women were included. DATA COLLECTION AND ANALYSIS: Assessment of inclusion/exclusion, quality assessment and data extraction were performed independently by at least two reviewers. Discrepancies were discussed in the presence of a third reviewer and a consensus reached. Quality assessment included method of randomisation, allocation concealment, blinding of participants and assessors, reporting of a power calculation, intention to treat analysis, and handling of dropouts. Data extraction included characteristics of participants, the intervention and control procedures, and outcomes. MAIN RESULTS: Seven RCTs were identified, four comparing rhCG and uhCG and three comparing rhLH and uhCG. There was no statistically significant difference between rhCG vs uhCG regarding the ongoing pregnancy/ live birth rate (OR 0.98, 95% CI 0.69 to 1.39), pregnancy rate, miscarriage or incidence of OHSS. There was no statistically significant difference between rhLH vs uhCG regarding the ongoing pregnancy/ live birth rate (OR 0.94, 95% CI 0.50 to 1.76), pregnancy rate, miscarriage or incidence of OHSS. The manufacturer of rhLH has decided not to further develop this product. rhCG was associated with a reduction in the incidence of local site reactions and other minor adverse effects (OR 0.47, 95% CI 0.32 to 0.70). AUTHORS' CONCLUSIONS: There is no evidence of difference in clinical outcomes between urinary and recombinant gonadotrophins for induction of final follicular maturation. Additional factors should be considered when choosing gonadotrophin type, including safety, cost and drug availability.

Management of severe ovarian hyperstimulation syndrome by ascitic fluid aspiration and intensive intravenous fluid therapy.

OBJECTIVE: To assess the value of intensive intravenous (IV) fluid therapy and ascitic fluid aspiration in the management of severe ovarian hyperstimulation syndrome. METHODS: Forty-two women with severe ovarian hyperstimulation syndrome were treated by ultrasonically guided transvaginal aspiration of ascitic fluid and IV fluid infusion. Ten women with the same condition treated conservatively constituted a comparison group. The main outcome measures included percentage change in hematocrit, creatinine clearance, and urine output before and after aspiration. The duration of hospital stay was compared between the groups. RESULTS: Marked improvement of symptoms and general condition followed soon after aspiration. Hematocrit readings decreased by 22%, creatinine clearance increased by 79.3%, and urine output increased by 220.7%. The average volume of aspirated fluid was 3900 mL. The average duration of hospital stay was 3.8 days in the treated women. In the comparison group, severe symptoms and electrolyte imbalance continued for an average of 9 days, and the average hospital stay was 11 days. CONCLUSION: Intensive IV fluid therapy and transvaginal aspiration of ascitic fluid are safe and effective in improving symptoms, preventing complications, and shortening the hospital stay in severe ovarian hyperstimulation syndrome.

Dummy embryo transfer: a technique that minimizes the problems of embryo transfer and improves the pregnancy rate in human in vitro fertilization.

Three hundred thirty-five patients selected for in vitro fertilization (IVF) were randomly divided into two groups. Group A (n = 167) was subjected to dummy embryo transfer (ET) before the start of IVF treatment to choose the most suitable catheter for each patient. Group B (n = 168) started their IVF treatment without dummy ET. Embryo transfer technique was difficult in 50 cases (29.8%) in group B, whereas no difficulty was met in group A. Pregnancy rate and implantation rate (22.8%, 7.2%) in group A were significantly higher than in group B (13.1%, 4.3%). The lower pregnancy rate in group B is due to the very low pregnancy rate (4%) in difficult ET cases. Dummy ET is a simple procedure that determines the most suitable ET catheter for each patient and avoids unexpected difficult and failed ET.

Ovarian superstimulation in the treatment of infertility due to peritubal and periovarian adhesions.

Forty-two women with peritubal and periovarian adhesions as the only cause of infertility were superstimulated with clomiphene citrate and human menopausal gonadotropin in 103 cycles. Superstimulation resulted in considerable increase in ovarian size, and change in the tubo-ovarian relationship. Twenty-two patients became pregnant, achieving a pregnancy rate of 21% per cycle and an overall rate of 52%. Hyperstimulation syndrome occurred in 85 cycles (82.5%). Four cases of tubal pregnancy were reported (3.8%). This line of treatment could be tried before resorting to microsurgery or in vitro fertilization and embryo transfer in patients with peritubal and periovarian adhesions with at least one patent tube.

Ultrasonically guided vaginal aspiration of ascites in the treatment of severe ovarian hyperstimulation syndrome.

This study included 11 cases of severe OHSS that were treated by transvaginal aspiration of the ascitic fluid guided by ultrasound. Immediate improvement of the symptoms and general condition as well as a significantly shorter hospital stay was noticed when compared with the control group. It is a safe and simple procedure that does not require anesthesia.

Autotransfusion of the ascitic fluid in the treatment of severe ovarian hyperstimulation syndrome.

Three cases of severe OHSS were treated by transvaginal aspiration of the ascitic fluid and autotransfusion of the aspirated fluid. Marked improvement of the symptoms, general condition, and urine output followed the aspiration shortly. No reactions were noticed during or after the autotransfusion. The blood parameters were corrected, and the general condition and urine output continued to improve. The procedure is simple, safe, and straightforward that showed a striking physiological success in correcting the maldistribution of fluid and proteins without the use of heterogeneous biological material.

Cryopreservation of the occasionally improved semen samples for intrauterine insemination: a new approach in the treatment of idiopathic male infertility.

OBJECTIVE: To assess the value of treating idiopathic male infertility by intrauterine insemination (IUI) of the occasionally improved cryopreserved semen. DESIGN: Two groups of idiopathic oligospermic patients were chosen at random and treated by IUI using processed fresh semen in group A and the best available cryopreserved semen samples pooled with fresh samples in group B. SETTING: Egyptian IVF-ET Centre, Maadi, CAiro, Egypt. PATIENTS, PARTICIPANTS: One hundred fifty infertile couples because of idiopathic oligoasthenospermia. INTERVENTION: Intrauterine insemination. MAIN OUTCOME MEASURE: The pregnancy rate was evaluated after an average of three treatment cycles. RESULTS: The pregnancy rate (PR) was significantly higher in group B when compared with group A. The improvement in the PR was highly significant in the subgroup of patients for whom reasonable semen samples could be collected and cryopreserved. CONCLUSIONS: Our study indicates that IUI with fresh semen pooled with cryopreserved occasionally improved semen samples for the treatment of oligoasthenospermia results in an improved PR.

Prospective controlled randomized study of in vitro fertilization versus intracytoplasmic sperm injection in the treatment of tubal factor infertility with normal semen parameters.

OBJECTIVE: To compare the results of IVF and intracytoplasmic sperm injection (ICSI) in tubal factor infertility with normal semen parameters. DESIGN: A prospective randomized study. SETTING: The Egyptian IVF-ET Center. PARTICIPANTS: One hundred sixteen patients infertile due to tubal factor were divided randomly into two groups. Group A(n = 58) was treated with IVF and group B(m = 58) was treated with ICSI. INTERVENTION: In vitro fertilization and ICSI. MAIN OUTCOME MEASURE: Pregnancy rate. RESULTS: In group A, 736 oocytes were retrieved and normal (two pronuclear [2pN] fertilization occurred in 477 oocytes (64.8%). In group B, 748 oocytes were retrieved, 572 metaphase II oocytes were injected, and 2PN fertilization occurred in 400 oocytes (70% per injected oocyte and 53.5% per retrieved oocyte). Clinical pregnancy was diagnosed in 18 patients in group A (31%) and 19 patients in group B (32.8%). There was no significant difference in the pregnancy rate between the two groups. The fertilization rate per retrieved oocytes was significantly higher in group A. CONCLUSIONS: Intracytoplasmic sperm injection does not offer a higher pregnancy rate as compared with IVF in the treatment of tubal factor infertility with normal semen.

The life span of sperm motility and pattern in cumulus coculture.

OBJECTIVE: To study the effect of cumulus cell coculture on human sperm motility, life span, and patterns. DESIGN: Controlled prospective study of 50 normal semen samples. Sperm motility and forward grade was observed in droplets of Ham's F-10 media with cumulus cell coculture and compared with sperm in droplets of Ham's F-10 only. SETTING: The Egyptian IVF-ET Center. MAIN OUTCOME MEASURES: Sperm motility, life span, and forward progressive pattern. RESULTS: The time course of loss of sperm motility in cumulus coculture was significantly slower than without cumulus. Also, the percentage of motile sperm with linear progressive motility of grade 4,3 was significantly higher in cumulus coculture. CONCLUSION: Cumulus cell coculture has a positive effect on prolongation of sperm motility life span and its forward progression.

The effect of sperm parameters on the outcome of intracytoplasmic sperm injection.

OBJECTIVE: To investigate the influence of sperm parameters on the fertilization and pregnancy rates in intracytoplasmic sperm injection (ICSI). DESIGN: A retrospective analysis of 130 cycles of ICSI performed for the treatment of male factor infertility. SETTING: The Egyptian IVF-ET Center. PARTICIPANTS: One hundred thirty couples with the diagnosis of male factor infertility or with previous failed fertilization in conventional IVF or subzonal sperm injection. INTERVENTION: Ovum pick-up and ICSI. MAIN OUTCOME MEASURE: Fertilization and pregnancy rates in relation to different semen parameters. RESULTS: A total of 1,433 oocytes were retrieved and 1,071 metaphase II oocytes were injected. Normal fertilization occurred in 620 oocytes (58%). Embryo transfer was done for 128 (98.5%) patients, and a total of 46 (35%) clinical pregnancies were achieved. There was no statistically significant difference in the fertilization or pregnancy rates between patients who had previously failed fertilization in conventional IVF, patients with subfertile semen, patients with semen between 1 and 10 x 10(6)/mL, and patients with semen < 1 x 10(6)/mL. There was also no significant difference in the fertilization and pregnancy rates between patients with < 95% or > 95% teratozoospermia. CONCLUSION: In ICSI, the fertilization and pregnancy rates are not affected by different semen parameters as long as morphologically well-shaped live sperms could be used for the injection.

Improvement of spontaneous pregnancy rate after stopping gonadotropin therapy for anovulatory infertility.

In a prospective study, 140 patients with infertility because of ovulatory factors (group A) were followed up for 6 months after failure to achieve pregnancy using human menopausal gonadotropin (hMG) therapy. They included cases of oligomenorrhea, polycystic ovarian disease (PCOD), and hypogonadotropic amenorrhea. They were treated with hMG alone or in combination with clomiphene citrate or gonadotropin-releasing hormone agonist analog. The control group (B) included 83 infertile patients because of similar ovulatory factors. They were followed up for 6 months not preceded by ovulation induction. The overall pregnancy rate (PR) in group A (20.7%) was significantly higher than group B (7.2%). The PR was significantly higher in oligomenorrhea and PCOD patients when compared with the control group. There was no significant difference in the hypogonadotropic group.

Oocyte quality in patients with severe ovarian hyperstimulation syndrome.

OBJECTIVE: To study the oocyte quality in patients with ovarian hyperstimulation syndrome (OHSS). DESIGN: Retrospective study. SETTING: The Egyptian IVF-ET Center. PATIENT(S): Forty-two patients who developed severe OHSS (group A) were studied for the mean number of oocytes retrieved, percentage of high-quality oocytes, embryo quality, and fertilization, implantation, and pregnancy rates; these patients were compared with an age-matched control group who did not develop OHSS (group B; n = 183) after superstimulation for IVF or intracytoplasmic sperm injection. INTERVENTION(S): In vitro fertilization and ICSI. MAIN OUTCOME MEASURE(S): Fertilization and pregnancy rates. RESULT(S): In group A, the mean number of oocytes retrieved was significantly higher, whereas the percentage of high-quality oocytes and the fertilization rate were significantly lower than that in group B. There were no statistically significant differences in the quality of embryos transferred or the implantation or pregnancy rate between the groups. The percentage of high-quality oocytes and the fertilization rate were significantly lower in patients with polycystic ovaries (PCO) in both groups. CONCLUSION(S): The inferior quality and maturity of oocytes in OHSS reduced the fertilization rate but did not affect the quality or the number of embryos transferred or the pregnancy rate. The effect on oocyte quality could be due to the prevalence of PCO in this group of patients.

Complications of medically assisted conception in 3,500 cycles.

OBJECTIVE: To investigate the incidence of complications in the use of assisted reproductive technology in the management of infertile couples. DESIGN: Retrospective study. SETTING: The Egyptian IVF & ET Center, Maadi, Cairo, Egypt. PATIENT(S): Two thousand nine hundred twenty-four patients underwent IVF-ET or intracytoplasmic sperm injection (ICSI) in 3,500 cycles. INTERVENTION(S): IVF-ET, ICSI, ejaculate sperm, epididymal sperm aspiration, and testicular sperm extraction. MAIN OUTCOME MEASURE(S): Complications of the procedure and complications of pregnancy in 702 patients. RESULT(S): Fifteen hundred ovum pickups for IVF-ET and 2,000 ovum pickups for ICSI were performed. Clinical pregnancy occurred in 1,078 patients (30.8%). Four groups of complications were identified. Complications of the procedure occurred in 291 patients (8.3%). Complications of pregnancy included ectopic pregnancy in 1.9%, heterotopic pregnancy in 0.2%. abortion in 20.6%, multiple pregnancy in 28%, pregnancy-induced hypertension in 10%, preterm labor in 21.5%, low birth weight in 30.5%, and intrauterine death in 2%. Coincidental complications occurred in five patients (0.15%). Other complications that were difficult to measure included psychological breakdown and socioeconomic problems. CONCLUSION(S): Assisted reproductive technology is effective for the management of infertility and has an acceptable incidence of complications. Complications rarely endanger the life of the patient. When this line of treatment is offered, the indications should be definitive. Patients should be monitored properly and measures should be taken to minimize the incidence of complications.

Controlled ovarian hyperstimulation and intrauterine insemination for treatment of unexplained infertility should be limited to a maximum of three trials.

OBJECTIVE: To investigate the optimum number of cycles of controlled ovarian hyperstimulation and intrauterine insemination in the treatment of unexplained infertility. DESIGN: Observational prospective study. SETTING: In vitro fertilization embryo transfer center. PATIENT(S): Five hundred ninety-four couples with unexplained infertility. INTERVENTION(S): Controlled ovarian hyperstimulation (COH), intrauterine insemination (IUI), in vitro fertilization (IVF), and intracytoplasmic sperm injection (ICSI). MAIN OUTCOME MEASURE(S): Cycle fecundity. RESULT(S): One to 3 cycles of COH/IUI were performed in 594 patients (group A) undergoing 1,112 cycles (mean, 1.9 cycles/patient). Up to 3 further trials (cycles 4-6) of COH/IUI were then performed in 91 of these women (group B), a total of 161 cycles (mean, 1.8 cycles/patient). A historical comparison group C consisted of 131 patients with 3 failed cycles of COH/IUI who underwent 1 cycle of IVF and ICSI at our center. In group A, 182 pregnancies occurred, with a cycle fecundity of 16.4% and a cumulative pregnancy rate (PR) of 39.2% after the first 3 cycles. In group B, 9 pregnancies occurred in cycles 4-6, with a cycle fecundity of 5.6%, significantly lower than that of group A (P<.001). The cumulative PR rose to 48.5% by cycle 6, a further increase of only 9.3%. In the women undergoing IVF and ICSI in group C, 48 pregnancies occurred, with a cycle fecundity of 36.6% per cycle, significantly higher than that of group B (P<.001). CONCLUSION(S): In unexplained infertility, the cycle fecundity in the first three trials of COH and IUI was higher than in cycles 4-6, with a statistically significant difference. Patients should be offered IVF or ICSI if they fail to conceive after three trials of COH and IUI.