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.

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.

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.

Intracytoplasmic sperm injection using microsurgically retrieved epididymal and testicular sperm.

OBJECTIVE: To evaluate treatment of couples who are infertile due to unreconstructable obstructive azoospermia with microsurgical epididymal sperm aspiration or testicular sperm and intracytoplasmic sperm injection (ICSI). DESIGN: Prospective. SETTING: The Egyptian IVF-ET Center in association with Cairo University. PATIENTS: Twenty-three couples who are infertile due to obstructive azoospermia in which reconstructive microsurgery failed or was not possible. INTERVENTIONS: Microsurgical epididymal or testicular sperm retrieval and ICSI in 24 cycles. MAIN OUTCOME MEASURES: Fertilization and pregnancies. RESULTS: All 24 cycles had successful fertilization and reached the ET stage. In microsurgical epididymal sperm aspiration cases, fertilization rate per metaphase II oocyte was 63% (109/ 172). Six patients became pregnant, including one set of twins and one set of triplets. One pregnancy resulted from the use of cryothawed epididymal sperm. In testicular sperm aspiration cases, the fertilization rate was 59% (32/54) and four clinical pregnancies resulted. CONCLUSION: The use of microepididymal sperm aspiration or testicular sperm aspiration in conjunction with ICSI provide a highly precise and efficient procedure for achieving pregnancy in cases of unreconstuctable obstructive azoospermia.

Transvaginal ultrasonic needle guided aspiration of pelvic inflammatory cystic masses before ovulation induction for in vitro fertilization.

Transvaginal aspiration of pelvic cystic inflammatory masses guided by a real time ultrasound vaginal transducer is described. The technique was successfully used in 32 patients to aspirate these masses before ovulation induction for in vitro fertilization (IVF). It is a safe and simple procedure that resulted in significantly higher ovarian response to stimulation for IVF, easier ultrasonic follow-up of the follicles, significant increase in the average number of oocytes per pick-up, and significant increase in the number of embryos per transfer when compared with the control group.

Recombinant follicle-stimulating hormone in the treatment of patients with history of severe ovarian hyperstimulation syndrome.

OBJECTIVE: To compare the low-dose recombinant FSH and hMG protocols in treatment of patients with history of severe ovarian hyperstimulation syndrome (OHSS). DESIGN: A prospective study on 22 patients with history of severe OHSS. Group A (n = 14) was treated with low-dose recombinant FSH 40 cycles and group B (n = 8) was treated with low-dose hMG in 26 cycles. SETTING: The Egyptian IVF-ET Center, Cairo, Egypt. PATIENT(S): Twenty-two patients with a history of severe OHSS. INTERVENTION(S): Ovulation induction. MAIN OUTCOME MEASURE(S): Estradiol, number of follicles, number of hMG ampules, pregnancy rate (PR), and the development of OHSS. RESULT(S): The cancellation rate, mean E2 level on day of hCG, mean number of days of stimulation, and the mean number of ampules per cycle were 10%, 523 +/- 166 pg/mL (conversion factor to SI unit, 3.671), 17.8 +/- 5.4, and 19 +/- 6.5 in group A and 19.2%, 554 +/- 152 pg/mL, 14.6 +/- 2.5, and 16.1 +/- 3.6 in group B, respectively. Treatment resulted in eight pregnancies (20% per cycle) and two abortions (25%) in group A. In group B, four pregnancies resulted (15.4% per cycle) and two patients aborted (50%). No cases of OHSS developed in both groups. There were no significant differences in all parameters between the two groups. CONCLUSION(S): Recombinant FSH low-dose protocol proved to be as effective as low-dose hMG in producing reasonable ovulation and PRS in polycystic ovary syndrome patients with a history of severe OHSS and the protocol was safe concerning the risk of development of OHSS.

Fertilization and pregnancy rates after intracytoplasmic sperm injection using ejaculate semen and surgically retrieved sperm.

OBJECTIVE: To compare the fertilization rates and pregnancy rates (PRs) in intracytoplasmic sperm injection (ICSI) using sperm from ejaculates of normal and abnormal semen, epididymal sperm, and testicular sperm of obstructive and nonobstructive azoospermic patients. DESIGN: Retrospective study. SETTING: The Egyptian IVF-ET Center. PATIENT(S): Three hundred fifty patients underwent 366 ICSI cycles. INTERVENTION(S): ICSI, epididymal sperm aspiration, and testicular biopsy. MAIN OUTCOME MEASURE(S): Fertilization rates and PRs. RESULT(S): Patients were divided into five groups according to the quality and source of sperm. Patients in group 1 underwent 102 cycles of ICSI using ejaculated abnormal semen, group 2 underwent 44 cycles using epididymal sperm, group 3 underwent 82 cycles using testicular sperm from obstructive azoospermia, group 4 underwent 80 cycles using testicular sperm from nonobstructive azoospermia, and group 5 underwent 58 cycles using normal semen. There was no significant difference in the fertilization rates and PRs among groups 1, 2, and 3. In group 4, the fertilization rate and PR were significantly lower than in all other groups. In group 5, the fertilization rate was significantly higher than in all other groups. CONCLUSION(S): The fertilizing ability of sperm in ICSI is highest with normal semen and lowest with sperm extracted from a testicular biopsy in nonobstructive azoospermia. There was no significant difference in fertilization rates and PRs between ejaculated sperm of different parameters and surgically retrieved sperm in obstructive azoospermia.

Ovarian superstimulation and intrauterine insemination for the treatment of unexplained infertility.

OBJECTIVE: To evaluate the efficacy of controlled ovarian hyperstimulation (COH) and IUI in the treatment of unexplained infertility. DESIGN: The pregnancy rate (PR) in patients with unexplained infertility treated by COH and IUI (group A) was compared with a no-treatment control (group B). SETTING: The Egyptian IVF-ET Center. PARTICIPANTS: Four hundred ninety-two patients with the diagnosis of unexplained infertility. INTERVENTION: Controlled ovarian hyperstimulation and IUI. MAIN OUTCOME MEASURES: Cycle fecundity per treatment cycle and PR per patient. RESULTS: In group A cycle fecundity was 20.1% per treatment cycle, and the PR was 34.7% per patient. In group B the PR was 8.9% per patient. Pregnancy rate per patient was significantly higher in group A when compared with the spontaneous PR in group B. CONCLUSION: Controlled ovarian hyperstimulation and IUI significantly increased the PR in patients with unexplained infertility when compared with a no-treatment control group.

Successful intracytoplasmic sperm injection without performing cytoplasmic aspiration.

OBJECTIVE: To compare the effect of cytoplasmic aspiration versus no aspiration before intracytoplasmic sperm injection (ICSI) on the rate of oocyte damage, fertilization rate, and embryo quality. DESIGN: A randomized prospective study on sibling oocytes. SETTING: The Egyptian IVF-ET Center, Cairo, Egypt. PARTICIPANTS: Fifty-eight patients who were infertile due to male factor who underwent 60 ICSI cycles. INTERVENTION: Intracytoplasmic sperm injection was performed on randomly allocated metaphase II oocytes with cytoplasmic aspiration in group I and without cytoplasmic aspiration in group II before sperm injection. MAIN OUTCOME MEASURE: Fertilization rate, oocyte damage rate, and embryo quality. RESULTS: Normal fertilization rate per injected oocyte was 61.4% in group I compared with 62.5% in group II. The damage rate per injected oocyte was 16.8% in group I compared with 4.6% in group II. Grade I embryos were 24.5% in group I compared with 48.5% in group II. CONCLUSION: Cytoplasmic aspiration before sperm injection in ICSI is not essential for oocyte activation. It did not improve the rate of normal fertilization. On the other hand, it increased the damaged oocyte rate and the rate of cytoplasmic fragments.

Multifetal pregnancy reduction: modification of the technique and analysis of the outcome.

OBJECTIVE: To modify the technique of multifetal pregnancy reduction and to study the outcome of reduced twins in comparison with nonreduced twins and high-order multiple gestations. DESIGN: Prospective controlled study. SETTING: The Egyptian IVF-ET Center, Cairo. PATIENT(S): Seventy-five patients with high-order multiple pregnancies resulting from assisted reproduction. Controls were 40 nonreduced twin pregnancies and 22 high-order multiple gestations. INTERVENTION(S): Transvaginal ultrasonically guided multifetal pregnancy reduction was performed. The first 30 cases were done using KCl as a cardiotoxic agent. The modified technique was used for the last 45 cases at an earlier gestational age (approximately 7 weeks) by eliminating the use of KCI and by aspirating the embryonic parts. MAIN OUTCOME MEASURE(S): Miscarriage rate, gestational age at delivery, birth weight, and pregnancy complications. RESULT(S): Using the modified technique, the miscarriage rate was 8.8% and 41 patients delivered between 32 and 39 weeks of gestation (mean+/-SD, 36.9+/-2.45 weeks). The mean (+/-SD) birth weight was 2,450.51+/-235.44 g. The miscarriage rate, fetal wastage rate, mean gestational age, and mean birth weight were similar in reduced and nonreduced twins and were significantly better than in nonreduced triplets and quadruplets. CONCLUSION(S): The modified technique of multifetal pregnancy reduction significantly improved outcomes, which were similar to those of nonreduced twins resulting from assisted reproduction and significantly better than those of nonreduced triplets and quadruplets.

Elevated levels of interleukin-2, soluble interleukin-2 receptor alpha, interleukin-6, soluble interleukin-6 receptor and vascular endothelial growth factor in serum and ascitic fluid of patients with severe ovarian hyperstimulation syndrome.

OBJECTIVE: To investigate the possible role of vascular endothelial growth factor, interleukin-2, soluble interleukin-2 receptor alpha, interleukin-6 and soluble interleukin-6 receptor in the pathogenesis of ovarian hyperstimulation syndrome. STUDY DESIGN: The study group consisted of 10 healthy women who developed severe ovarian hyperstimulation syndrome, group A (n=10), following ovarian stimulation by long GnRHa/hMG protocol for IVF. A control group B=10 patients underwent stimulation with the same protocol and did not develop OHSS. Blood and ascitic fluid samples were assayed for VEGF, IL-2, sIL-2Ralpha, IL-6 and sIL-6R by ELISA. RESULTS: The mean serum levels of IL-2, sIL-2Ralpha, IL-6, sIL-6R and VEGF in OHSS group were 297.5+/-190, 6588+/-5566, 40.6+/-16.6, 5280+/-3326 and 492+/-165 pg/ml as compared to 50.8+/-17.4, 1100+/-391.6, 8.5+/-3.5, 516+/-342 and 167+/-31.3 pg/ml in the control group, respectively, P<0.001. The mean ascitic fluid IL-2, sIL-2Ralpha, IL-6, sIL-6R and VEGF in the OHSS group were 282.5+/-191.5 pg/ml, 26020+/-13 995, 90.5+/-36, 14900+/-2789 and 660+/-359 pg/ml as compared to 32+/-14.8, 1206+/-429.4, 12.6+/-1.7, 614+/-240 and 151+/-20.5 pg/ml, respectively, P<0.001. CONCLUSIONS: The significantly high levels of VEGF in patients with severe OHSS suggest that VEGF is a major capillary permeability agent in OHSS. Elevated levels of IL-6 in serum and peritoneal fluid support the hypothesis that IL-6 may serve as a marker of OHSS. Although serum and ascitic fluid levels of IL-2 were elevated, accumulating evidence does not support a pivotal role for IL-2 in the pathogenesis of OHSS. However, it may have a peripheral role in mediating an increase in vascular permeability. Soluble IL-2Ralpha and sIL-6R may be considered to be involved in OHSS. However, the patho-physiologic mechanism is the subject of further investigations. Clinical application of VEGF-receptors in the management of OHSS is awaited with interest.