Multiple pregnancies: what action should we take?
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Publications and source records attributed to C C Coddington.
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OBJECTIVE: To determine if exposure of human gametes to macrophage secretory products reduces sperm binding to the zona pellucida, and to determine which cytokine(s) may be responsible for this effect. METHODS: A human macrophage cell line was cultured and either activated with lipopolysaccharide for 2 hours and then washed or left unactivated. Culture-conditioned media from activated or unactivated cells was used in hemizona assay. Hemizonae were incubated with sperm suspended in culture medium from either unactivated macrophages or activated macrophages, with the matching hemizona incubated with sperm suspended in control medium. Matching hemizonae were incubated with sperm suspended in unactivated macrophage medium paired with sperm suspended in activated macrophage culture medium. Conditioned medium from activated macrophages was found to have elevated levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta, and transforming growth factor-beta, therefore, gametes were also exposed to these cytokines followed by the hemizona assay. After each incubation, the number of sperm tightly bound to the outer surface of each hemizona was determined. RESULTS: Exposure of gametes to activated and unactivated macrophage culture-conditioned media significantly decreases sperm binding to the zona pellucida, with medium from activated macrophages inducing the greatest effect (P < .05). Exposure of sperm to TNF-alpha significantly impaired sperm binding (P < .05), whereas other cytokines tested had no effect. CONCLUSION: These results suggest that macrophage secretory products in the basal and activated state may be a factor in endometriosis-associated infertility through the interference of sperm binding to the zona pellucida, and that TNF-alpha is a key cytokine responsible for this effect.
OBJECTIVE: To compare the diagnostic accuracy, pain scores, and procedure length of outpatient hysteroscopy (OHS), hysterosalpingography (HSG), and saline infusion hysterosonography (SIS) for evaluation of the uterine cavity of infertile women. DESIGN: Prospective, randomized, investigator-blind study. SETTING: Tertiary infertility clinic. PATIENT(S): Forty-six consecutive infertile women. INTERVENTION(S): Outpatient HSG, OHS, and SIS, followed by operative hysteroscopy (HS). MAIN OUTCOME MEASURE(S): Uterine abnormalities, procedure length, and subjective pain. RESULT(S): Fifty-nine percent of infertile subjects were found to have an abnormality on at least one of three outpatient uterine evaluations. When compared with the case of definitive operative HS, 60% of abnormalities were correctly classified by HSG, 72% by OHS, and 52% by SIS (P: NS). When comparing all combinations of 2 outpatient screening tests to operative hysteroscopy, 68% were correctly classified by HSG/OHS, 58% by HSG/SIS, and 64% by OHS/SIS (P: NS). The average time length for the OHS was 9.1 min., which was significantly greater than for both HSG (average, 5.3 min) and SIS (average, 6.1 min.) (P<.0001 for both). HSG and SIS were not statistically different regarding procedure time length. The average pain score (0-10) for SIS was 2.7, compared with 5.8 and 5.3 for HSG and OHS, respectively. Both HSG and OHS mean pain scores were significantly greater than the SIS mean. CONCLUSION(S): OHS, SIS, and HSG were statistically equivalent regarding evaluation of uterine cavity pathology in infertile women.
There are many considerations in the surgical treatment of patients with infertility. Of prime importance is the baseline condition of the tubes and skill of the surgeon. With further advances in the understanding of the process of fertilization and implantation, it is anticipated that the use of surgical methods and application of new technologies will continue to improve fecundity for patients with infertility.
This article serves as a general review of laparoscopy and hysteroscopy. Subjects covered include equipment and instrumentation, use of laser and electrosurgery, surgical technique, and complications.
OBJECTIVE: To determine the cost-effectiveness, safety, and success of microsurgical tubal anastomoses performed by minilaparotomy as an outpatient. DESIGN: Retrospective. SETTING: Military tertiary care medical center. PATIENT(S): Seventy consecutively seen women of reproductive age who were undergoing surgical reversal of sterilization from August 1, 1993, through August 1, 1995. INTERVENTION(S): Microsurgical sterilization reversal by minilaparotomy was performed as an inpatient (group 1, 47 patients) or as an outpatient (group 2, 23 patients). MAIN OUTCOME MEASURE(S): Cost, complication rate, pregnancy rate. RESULT(S): The procedure cost more for inpatients ($3,116) than for outpatients (!,456). Pregnancy rates were similar (56% in group 1 vs. 75% in group 2). There was only one complication in the series. CONCLUSION(S): Outpatient microsurgical sterilization reversal performed by minilaparotomy is as safe and effective as the inpatient procedure and is less expensive.
OBJECTIVE: To investigate the diagnostic accuracy of microlaparoscopy in comparison to laparoscopy with a standard 10-mm laparoscope. DESIGN: Prospective evaluation by two independent observers. SETTING: Academic Medical Center. PATIENT(S): Ten patients scheduled to undergo diagnostic laparoscopy for the indications of infertility and/or chronic pelvic pain. INTERVENTION(S): Two surgeons were present for each operation. Diagnostic laparoscopy was performed using the Microlap 2-mm laparoscope (Imagyn Medical Inc., Lagun Niguel, CA). Standard diagnostic laparoscopy was then performed using a 10-mm laparoscope. After each procedure, each surgeon reported his or her observations in a confidential manner to a third person to record. MAIN OUTCOME MEASURE(S): Endometriosis and adnexal adhesions were staged. Observations made with the microlaparoscope were compared with those obtained with a standard 10-mm laparoscope for each surgeon. The observations of both surgeons were also compared with each other's to evaluate interobserver differences. RESULT(S): Operative findings reported by each individual surgeon using the microlaparoscope correlated with the operative findings reported using the larger laparoscope. Scores for both endometriosis and adnexal adhesions did not differ in any significant way. Endometriosis scores differed by no more than 6 points, and adhesion scores differed by no more than 2 points, with no subsequent change in severity classification for either finding. Furthermore, when comparing the additional operative findings of the two surgeons, no difference was noted when using either the microlaparoscope or a standard 10-mm laparoscope. CONCLUSION(S): The diagnostic accuracy achieved with microlaparoscopy is comparable to that achieved with standard 10-mm laparoscopy.
OBJECTIVE: To identify factors influencing the development of endometrial autografts in a monkey model of endometriosis. DESIGN: Prospective, comparative study. SETTING: Animal research unit. SUBJECTS: Thirty regularly cycling cynomolgus monkeys in three groups of 10 each. INTERVENTIONS: Endometrium was minced and spilled into the cul-de-sac in group 1. In group 2, the tissue additionally was digested enzymatically. In group 3, the tissue was incubated with a protease inhibitor. MAIN OUTCOME MEASURES: Staging laparotomies after 3 weeks and 3 months. RESULTS: In groups 1, 2, and 3, moderate or severe disease was seen in eight, two, and four monkeys, respectively, after 3 weeks and in eight, three, and two monkeys, respectively, at 3 months. CONCLUSIONS: An intact structure leads to ectopic implantation of endometrial fragments in most cases. Conversely, enzymatic digestion of endometrial fragments and treatment with proteinase inhibitor impair ectopic growth. Intrinsic endometrial factors that influence extracellular matrix remodeling may play a role in the pathogenesis of human endometriosis.
To determine the ovarian response to a fixed dose of gonadotrophin-releasing hormone (GnRH) administered s.c. at four different pulse frequencies, 20 patients with hypothalamic amenorrhoea were treated over 41 cycles using a dose of 20 ng/kg/pulse. These patients were randomly assigned to receive GnRH at pulse frequencies of 60, 90, 120 or 180 min. GnRH was administered s.c. using portable infusion pumps. Subjects were paid volunteers with a diagnosis of hypothalamic amenorrhoea. All patients had low to less than detectable serum concentrations of luteinizing hormone and follicle stimulating hormone on 8 h serial sampling, and normal serum concentrations of prolactin and androgen, including androstenedione, testosterone and dihydroepiandrosterone sulphate. Six of the 20 patients were enrolled in the protocol to achieve a pregnancy, while 14 were volunteers using a barrier method of contraception. Highest ovulation rates were achieved using pulse frequencies of 90 and 120 min (60 and 88% of cycles respectively). Ovulation occurred significantly less often with frequencies of 60 and 180 min (12 and 38% respectively; P </= 0.05). Pregnancy was achieved in four of the six patients who desired a pregnancy at pulse frequencies of 90 (three out of three) and 120 (one out of one) min. No pregnancies occurred at pulse frequencies of 60 (none out of one) and 180 (none out of one) min. When ovulatory cycles were considered, oestradiol concentrations were not different among pulse frequencies but varied significantly between ovulatory and anovulatory cycles. Integrated luteal progesterone concentrations for 90 and 120 min frequencies (118.26 +/- 25.89 and 125.15 +/- 32. 10 ng/ml/luteal phase respectively) were significantly higher than for 60 and 180 min (80.1 +/- 48.2 and 42.75 +/- 26.48 ng/ml/luteal phase respectively). Ovulation may be induced by a broad range of pulse frequencies. Pulse frequencies of 90 or 120 min for s.c. GnRH appear to induce more reliably the sequence of follicular development, ovulation and normal luteal function than frequencies of either 60 or 180 min. Significantly higher ovulation rates occurred at 90 and 120 min by s.c. administered GnRH.
OBJECTIVE: To determine the contribution of estrogen in the development of pelvic adhesions during myometrial surgery. DESIGN: A randomized, prospective study in the nonhuman primate. SETTING: A primate colony, Department of Obstetrics and Gynecology, Eastern Virginia Medical School. INTERVENTIONS: All primates were assigned prospectively to one of three treatment groups: [1] GnRH analogue (GnRH-a), [2] mifepristone, or [3] vehicle control. After 3 months of treatment, a standard uterine fundal hysterotomy, for full thickness endometrial biopsy, was performed at the time of exploratory laparotomy, with subsequent scoring of utero-omental adhesions to the hysterotomy site at a future staging procedure based upon adhesion area, vascularity, and tenacity. Serum was drawn on the day of surgery for E2 determination. Endometrial height, from the surface interface between the endometrium and myometrium, was used as a bioassay of estrogen activity. RESULTS: The hypoestrogenic (GnRH-a) group and the mifepristone group had significantly fewer utero-omental adhesions compared with the normally cycling control monkeys as measured by a lower adhesion score. Similarly, the endometrial thickness was significantly reduced in the GnRH-a and mifepristone groups (one-third) compared with the cycling controls, demonstrating the effects of either hypoestrogenism or noncompetitive estrogen antagonism. Serum E2 on the day of surgery was predictive of the postoperative adhesion score by both a regression analysis and analysis of covariance. CONCLUSIONS: The actions of E2 seem to have a dramatic effect on the formation of pelvic adhesions after myometrial surgery.
OBJECTIVE: To examine whether placental protein 14 (PP14) may affect directly those sperm functions crucial to fertilization and early embryo development. DESIGN: In these prospective studies, we evaluated semen samples of fertile men incubated under capacitating conditions with and without PP14. SETTING: Academic tertiary institution. INTERVENTIONS: Biologically active PP14 was purified from human midtrimester amniotic fluid by anion exchange and immunoaffinity chromatography. After separation of the motile fraction, spermatozoa were incubated for 30 minutes with or without PP14 (concentration range of 0.01 to 100 micrograms/mL), washed, and then aliquots were prepared for use in the different assays. Human sperm-zona pellucida (ZP) binding was assessed using the hemizona assay (HZA) in a 4-hour gametes coincubation period. Sperm motility parameters were evaluated using a computerized semen analyzer. The acrosome reaction (AR) was determined by fluorescein isothiocyanate-conjugated Pisum sativum agglutinin and indirect immunofluorescence. MAIN OUTCOME MEASURES: Sperm-ZP binding, sperm motility patterns, and AR. RESULTS: Preincubation of sperm (and not the hemizonae) with PP14 produced a significant and dose-dependent inhibition of binding in the HZA. Monoclonal antibodies generated against PP14 showed no direct effect in the HZA and partially neutralized the inhibitory activity of PP14 in the HZA. Insulin-like growth factor binding protein-1 (IGFBP-1), an endometrial stromal cell product, showed no effect in the HZA. Neither PP14 nor IGFBP-1 interfered with sperm motility parameters or the AR. CONCLUSIONS: Placental protein 14 produced a potent, fast, and dose-dependent inhibition of binding of human spermatozoa to the human ZP without affecting other prefertilization events (i.e., hyperactivated motility or AR). The detrimental effect on sperm-zona interaction seems to be specific for this endometrial epithelial protein (not observed with an endometrial stromal product) and may have fundamental bearance to the fertilization process thus providing a mechanism for endometriosis-related infertility.
To evaluate the role of the Tru-Trax cervical mucus penetration testing of prognosis of patient performance in in-vitro fertilization (IVF) and to examine its use as a possible screening test prior to IVF, 133 couples presenting with infertility prospectively underwent in-vitro cervical mucus penetration testing. Of these, 66 couples subsequently underwent IVF. The penetration distance of the vanguard spermatozoa in both human and bovine mucus was compared to the fertilization and pregnancy rates during IVF. The fertilization rates in couples with normal human mucus penetration (n = 42, 80.6%) were higher than those with abnormal scores (n = 24, 49.6%; P < 0.001). Similarly, the fertilization rates in those couples with normal bovine mucus penetration (n = 50, 77.5%) were higher than those with abnormal results (n = 16, 40.0%; P < 0.001). Fertilization rates and penetration scores were highly correlated for both human (r = 0.66; P < 0.0001) and bovine (r = 0.66; P < 0.0001) mucus. However, the predictive value of an abnormal result for failed fertilization was poor for both human and bovine penetration, since 83.33 and 81.25% fertilized respectively. Pregnancy rates did not differ among couples with normal and abnormal penetrations. In conclusion, in-vitro cervical mucus penetration testing was highly correlated with fertilization rates in IVF. However, the poor predictive value of an abnormal result may limit the value of this test for generalized pretreatment screening.
OBJECTIVES: To determine the effectiveness of two different surgical membranes in preventing postoperative adhesions as compared with control and to evaluate the benefit as compared with "second-look" adhesiolysis. DESIGN: A randomized, prospective, crossover study. SETTING: A colony of individually caged non-human primates, Department of Obstetrics and Gynecology, Eastern Virginia Medical School Norfolk, Virginia. INTERVENTIONS: Hysterotomy or adhesiolysis at the time of exploratory laparotomy, with subsequent scoring of adhesions based on area, vascularity, tenacity, and adhesion score. RESULTS: The combined crossover data reveal that both surgical barriers are superior in adhesion prevention to microsurgical technique alone. Expanded polytetrafluoroethylene (Gore-Tex Surgical Membrane; WL Gore and Associates, Flagstaff, AZ) was better than oxidized regenerated cellulose (Interceed; Johnson and Johnson Medical, Inc., Arlington, TX) with respect to adhesion area, tenacity, and vascularity, with a significant improvement in the total adhesion score. Second-look adhesiolysis resulted in significant adhesion reduction in the control group, making second-look adhesiolysis statistically similar to the use of either barrier alone (without subsequent adhesiolysis). Gore-Tex removal does not result in adhesion formation as determined by third-look surgery. CONCLUSIONS: Both Interceed and Gore-Tex show a reduction in the prevention of postsurgical adhesions after hysterotomy incisions, as compared with microsurgical technique alone. Second-look adhesiolysis is as effective as either barrier in the reduction of permanent pelvic adhesions.
To determine the distribution of results of an in-vitro cervical mucus penetration system employing both human and bovine mucus (Tru-Trax) in a general infertility population, 133 couples prospectively underwent in-vitro and post-coital testing of cervical mucus. The distribution of Tru-Trax results in couples with normal semen analyses and Insler scores showed significantly greater penetration in bovine (22.3 +/- 6.0 mm) than in human mucus (20.3 +/- 5.4 mm) (P < 0.001). However, the lower limit of the 95% confidence interval of the normal population with either type of mucus was approximately 10 mm. This limit was significantly lower than that described by the kit manufacturer. The predictive value for post-coital tests using human mucus in the Tru-Trax system was good (> 90%) in all groups. The overall penetration into either human or bovine mucus was significantly correlated with the percentage of motile spermatozoa in the semen sample (P < 0.001). In conclusion, in-vitro cervical mucus penetration tests with the Tru-Trax system are related to in-vivo post-coital tests, although the lower limit of the range of anticipated results in the normal population was significantly lower than that described by the manufacturer. The ultimate value of this type of testing will await clinical trials which evaluate clinical end-points such as pregnancy rates.
Two cases of cervical myoma were treated with combined medical/surgical therapy using a gonadotropin releasing hormone agonist (GnRH-a) and transvaginal cervical myomectomy. Patients were treated with depot GnRH-a (leuprolide acetate) for two months followed by myomectomy. This approach allowed successful treatment with short hospitalization (< 24 hours). Potential benefits of this regimen include decreased intraoperative blood loss, outpatient management, decreased morbidity, decreased hospital expense and preservation of reproductive potential by avoiding hysterectomy.
Eight infertility patients with proximal tubal occlusion by HSG and at least one other independent method underwent falloposcopy to evaluate the etiology of uterotubal occlusion. Patency was established in 9 of 12 tubes evaluated. Falloposcopy revealed 5 tubes with multiple or extensive intratubal lesions that would be unsuitable for unilocular tubal resection with subsequent reanastomosis. In addition, 5 tubes were visually normal or had only minor pathological changes (2 of these patients became pregnant). Only 2 of the tubes examined in a single patient would be considered candidates for microsurgical correction at laparotomy. Falloposcopy will become a useful adjunct in the evaluation of the patient with suspected tubal infertility. It provides information regarding the condition of the tubal mucosa that is unavailable by any other technique, adding precision to surgical techniques when they are deemed necessary while directing other patients to assisted reproductive technologies. However, falloposcopy is still in its infancy and data from larger studies are needed.
The objective of this prospective study was to examine the ability of the hemizona assay (HZA) to predict fertilization outcome of mature, pre-ovulatory oocytes under in-vitro fertilization (IVF) conditions. Since a large number of patients were evaluated over a long period, the power of the HZA to prognosticate fertilization results in the same and subsequent (consecutive) IVF cycles of those same patients was assessed. For IVF, only metaphase II oocytes were used. For the HZA, both fresh oocytes donated by patients at the time of IVF and oocytes recovered from surgically removed ovarian tissue (and salt-stored) were used, and bisected by micromanipulation techniques. Matching hemizonae were co-incubated either with spermatozoa from the patient (test) or from a fertile man (control) for 4 h. The number of spermatozoa tightly bound to the zona was counted. Patients (n = 112) were divided into two groups based on HZA results (expressed as HZA index or HZI): HZI > or = 30% (n = 72) and < 30% (n = 40). The patients with HZI < 30% had significantly lower fertilization rates in both the HZA-IVF cycle and in subsequent cycles compared to patients with HZI > or = 30% (P < 0.03). Linear discriminant analysis indicated the HZA to have a sensitivity of 84%, and positive and negative predictive values of 85 and 70% respectively, for prediction of fertilization outcome in a total of 233 cycles. It was concluded that the HZA is a good predictor of fertilization rate in vitro, and can be used in the IVF setting to supply additional clinical information in male-factor patients.
Romano-Ward syndrome is a subtype of prolonged QT syndrome with autosomal dominant inheritance. Stress-induced syncope and sudden death are secondary to ventricular tachydysrhythmias. A case report of Romano-Ward syndrome complicating pregnancy is presented. Successful therapy with propranolol for life-threatening dysrhythmias was achieved. An excellent neonatal outcome occurred.