Pregnancies in primary amenorrhea with normally developed secondary sex characteristics.

We report herein 11 pregnancies in patients with primary amenorrhea and normally developed secondary sex characteristics. All patients were fully investigated, and their ovaries as visualized by laparotomy or laparoscopy were found to be small. Ovarian biopsy revealed numerous unstimulated primordial follicles. The hormonal profiles showed hypoestrogenism with atrophic endometrium. Human gonadotropins were used in large amounts in order to achieve pregnancy. Two patients responded in all treatment cycles with menses. The remainder failed to respond to all treatment cycles. All patients became pregnant and carried their pregnancies normally to term. There were four sets of twins and seven single births. Of fifteen newborns, one died of congenital heart disease.

Ultrasound measurement of ovarian follicles stimulated by human gonadotropins for oocyte recovery and in vitro fertilization.

Ultrasonic monitoring of ovarian follicles and estimation of serum estradiol (E2) were performed in 51 patients in whom oocyte aspiration for in vitro fertilization was planned. All patients received human menopausal gonadotropin and human chorionic gonadotropin. The daily growth rates of ovarian follicles were recorded ultrasonically for 6 days prior to aspiration. Serum plasma E2 was determined daily during the same period. Follicular dimensions based on the volume of aspirated fluid correlated very well with the ultrasonic measurements. Follicular growth was correlated with increasing peripheral blood E2 levels. The mean follicular diameter increased from 10.8 mm 6 days before aspiration to a maximum of 16.0 mm on the day of presumptive ovulation in a group of patients characterized as low E2 responders. In normal and high E2 responders, the values were from 9.7 mm and 10.5 mm to 16.9 mm and 17.6 mm, respectively. The mean sizes of the follicles by ultrasound 20 hours before laparoscopy were 16.0 mm for the right ovary, 16.6 mm for the left ovary, and 18.5 mm in patients with only one ovary. At laparoscopy the mean diameters calculated from the volume of the aspirated fluids were 17.5 mm, 17.4 mm, and 19.3 mm, respectively. Multiple follicles developed in all but 2 of the 51 patients.

Ureaplasma urealyticum in semen: is there any effect on in vitro fertilization outcome?

OBJECTIVE: To determine the effect of the presence of Ureaplasma urealyticum in semen on IVF outcome (fertilization, pregnancy, and abortion rates). DESIGN: Prospective study. SETTING: Private IVF unit in Athens, Greece. PATIENT(S): One hundred ninety-one asymptomatic men with normal semen parameters whose wives underwent an IVF cycle. INTERVENTION(S): Culture of semen for U. urealYticum on the day of oocyte retrieval. MAIN OUTCOME MEASURE(S): Fertilization, pregnancy, and abortion rates after IVF. RESULT(S): Ninety-six (86%) of the 112 women whose husbands' semen was negative for U. urealyticum and 65 (82%) of the 79 women whose husbands' semen was positive for U. urealyticum underwent ET. The pregnancy rate (PR) was 20% (19/96) in the negative group and 17% (11/65) in the positive group. An increased incidence of abortions (6/11) was observed in the positive group (abortion rate, 54%), compared with 21% (4/19) in the group of women whose husbands' semen was negative for U. urealyticum. CONCLUSION(S): Fertilization rates and PRs may not be affected by the presence of U. urealyticum in semen on the day of oocyte retrieval. It can be presumed that the semen preparation for IVF cleanses the semen of U. urealyticum. On the other hand, the higher abortion rate in the U. urealyticum-positive group might be related to maternal factors, such as an existing U. urealyticum infection or one contracted after conception.

Correlation of human menopausal gonadotropin/human chorionic gonadotropin stimulation and oocyte quality in an in vitro fertilization program.

One hundred forty-seven cycles in normal ovulatory patients are reported. All were stimulated with human menopausal/human chorionic gonadotropin. Three estrogen responses were identified: normal, high, and low. Patients who achieved pregnancy formed a fourth category, the pregnancy group. The number of preovulatory and immature oocytes, the preovulatory and immature oocytes that fertilized normally or abnormally, the ones that cleaved in culture, and the ones that were transferred were used as parameters to compare quality of the oocytes in each of the estrogen responders. No significant differences were found in any of them. Abnormal zonae pellucidae are described as possibly due to overmaturation of the follicle. No significant difference in the proportion of abnormal zonae in the different categories was found.

Pregnancy results after ovum donation following one to seven embryo transfers.

OBJECTIVE: To determine whether failure to achieve pregnancy after repeated ET after ovum donation was due to an endometrial defect or to the embryo quality. DESIGN: Retrospective data analysis. SETTING: A private infertility center. PATIENT(S): Four hundred sixty-seven donors (513 cycles) undergoing IVF donating oocytes to 266 recipients (423 cycles). INTERVENTION(S): Hormonal endometrial preparation with increasing dosages of valerate E2 (2,4, and 6 mg) and 100 mg of P. MAIN OUTCOME MEASURE(S): Pregnancy rates (PRs) and abortion rates in patients undergoing one to seven ETs after ovum donation. RESULT(S): Pregnancy rates in recipients that had one or two ETs were significantly higher (34.8%) compared with those of recipients having three or more ETs (15.1%). Abortion rates were significantly higher (54.5%) in recipients repeating more than three ETs than in the recipients having one or two ETs (29.1%). CONCLUSION(S): Recipients that had failed to establish a pregnancy after two ETs had a lower PR in successive attempts, possibly because of a defect of their endometrial lining.

Correlation of serum and follicular fluid concentrations of placental protein 14 and CA-125 in in vitro fertilization-embryo transfer patients.

OBJECTIVE: To study serum and follicular fluid (FF) concentrations of placental protein 14 (PP14) and CA-125 in patients participating in an IVF-ET program. DESIGN: Determination in serum and FF on the day of hCG administration, day of oocyte retrieval, and on ET day of PP14 and CA-125. SETTING: Second Department of Obstetrics and Gynecology of the University of Athens; Euromedica IVF Unit; and Hellenic Pasteur Institute. PATIENTS: Thirty-three patients undergoing IVF-ET divided in three groups: 8 with conception, 18 with fertilized oocytes but no conception, and 7 without fertilized oocytes. INTERVENTIONS: All patients underwent an ovarian stimulation with a short protocol of GnRH analogue-pure-FSH-hMG. Three blood probes were collected from each patient, on the day of hCG administration, on retrieval day, and on ET day, respectively, whereas FF was collected on retrieval day. MAIN OUTCOME MEASURES: Determination in serum and FF of CA-125 and PP14. RESULTS: On the day of oocyte retrieval, both mean values of serum PP14 and CA-125 were significantly higher in conceptional than nonconceptional cycles. On the day of ET, the mean values of serum PP14 increased significantly in conceptional cycles whereas CA-125 showed no difference. The mean concentration of PP14 in FF was significantly higher in conceptional cycles whereas there was no significant change in the mean concentration of FF CA-125. CONCLUSIONS: In conceptional cycles after IVF, PP14 increases in serum significantly from hCG day to ET day compared with nonconceptional cycles, whereas CA-125 increases from hCG day to oocyte retrieval day and decreases on ET day. In FF, PP14 was increased in conceptional cycles, whereas CA-125 in FF showed no change.

The effect of pentoxifylline on sperm motility, oocyte fertilization, embryo quality, and pregnancy outcome in an in vitro fertilization program.

OBJECTIVE: To study the effect of pentoxifylline on sperm motility, oocyte fertilization, embryo cleavage, and quality as well as pregnancy outcome on asthenospermic patients participating in an IVF program. DESIGN: Prospective randomized study. SETTING: Private IVF unit. PATIENTS: Ninety-seven couples, 24 of whom were repeating IVF. Two semen specimens were obtained from each patient and each specimen was divided equally into two parts, nontreated (control semen) and pentoxifylline-treated (treated semen). MAIN OUTCOME MEASURE: Sperm progressive motility, oocyte fertilization. RESULTS: Overall and progressive motility did not differ significantly between the two semen specimens. There was a significant increase in the progressive motality of the pentoxifylline-treated semen compared with control semen. No significant difference was noticed between control and treated semen in fertilization rate, cleavage rate, embryo quality, and pregnancy rate. The percentage of patients who fertilized only with control semen (9.3%) was not significantly different from that of patients who fertilized only with treated semen (10.3%). Couples who were repeating IVF did not show significant difference in fertilization between the present study and previous attempts. CONCLUSION: Our results showed that although the sperm progressive motility is improved after pentoxifylline treatment, it is doubtful whether this effect is of any clinical significance.

Interleukin-1beta and interleukin-1alpha may affect the implantation rate of patients undergoing in vitro fertilization-embryo transfer.

OBJECTIVE: To investigate whether interleukin-1beta (IL-1beta) and interleukin-1alpha (IL-1alpha) affect the implantation rate of patients undergoing IVF-ET. DESIGN: Follicular fluid and serum were obtained on the day of hCG administration, the day of oocyte retrieval, and the day of embryo transfer. SETTING: Cellular immunology laboratory in a research institute, a high technology IVF unit in a medical center, and a university hospital. PATIENT(S): Thirty-three women who were undergoing IVF-ET. MAIN OUTCOME MEASURE(S): IL-1beta and IL-1alpha were measured by specific ELISA and their levels were correlated with the implantation rate. RESULT(S): Classification of IVF-ET patients according to their implantation rate revealed significantly higher amounts of follicular fluid IL-1beta in the implantation versus nonimplantation cycles (68.5+/-24.6 pg/mL versus 20.5+/-13.4 pg/mL); The difference between the level of IL-1alpha in the two groups was not statistically significant(11.6+/-5.1 pg/mL versus 7.3+/-1.9 pg/mL). In parallel, systemic FSH/hMG-dependent IL-1beta and IL-1alpha production was observed in implantation cycles but not in nonimplantation cycles. Statistically significant IL-1beta and IL-1alpha production was observed after administration of hCG. CONCLUSION(S): Gonadotropins used during IVF-ET induce local and systemic production of IL-1beta and IL-1alpha. In addition, the implantation rate for IVF-ET patients who have detectable serum concentrations of IL-1beta and IL-1beta on the day of hCG administration could be higher than the rate for IVF-ET patients who do not have detectable concentrations of these cytokines.

Discordant secretion of pregnancy specific beta 1-glycoprotein and human chorionic gonadotropin by human pre-embryos cultured in vitro.

OBJECTIVE: To study and compare the secretion of pregnancy specific beta 1-glycoprotein (SP1) and human chorionic gonadotropin (hCG) by human pre-embryos, cultured in vitro, with their respective morphological development. DESIGN: Spare human pre-embryos from randomly selected women participating in a program of in vitro fertilization (IVF) were studied prospectively. SETTING: Pre-embryos were cultured, and hormone release was determined in academic research laboratories. PATIENTS, PARTICIPANTS: Pre-embryos (n = 108) cultured for 14 days after fertilization in Ham's F-10 medium (GIBCO Ltd., Paisley, Scotland) were observed, and hCG and SP1 were measured in the culture media at regular intervals. MAIN OUTCOME MEASURES: Discordant secretion of SP1 and hCG. RESULTS: Of the 98 bipronucleate pre-embryos, 53.6% formed blastocysts, 17.3% of which hatched. Human chorionic gonadotropin was detected from day 7 after fertilization concomitantly with blastocyst formation, thereafter showing a logarithmic increase (maximum 10,650 mIU) until the first signs of embryonic disintegration. Pregnancy-specific beta 1-glycoprotein release started 3 to 4 days after fertilization independently of the morphological development and the future production of hCG, thereafter displaying a nonlogarithmic increase (maximum 41 ng). CONCLUSIONS: Hormone secretion and morphological development are unique for each pre-embryo. Human chorionic gonadotropin and SP1 seem to have different biochemical and physiological regulation.

What is a pregnancy? A question for programs of in vitro fertilization.

Pregnancy outcome in studies of normal reproduction and in programs of in vitro fertilization (IVF) is usually classified as "chemical beta-human chorionic gonadotropin (beta-hCG) abortion," "trimester abortion," and "term delivery." The distinction between a chemical beta-hCG abortion and a first-trimester abortion is not clearly stated in the literature, although such terms are commonly used. It is proposed that in programs of IVF pregnancy outcome be classified as "menstrual abortion," "preclinical abortion," "clinical abortion," or "viable pregnancy." Pregnancy outcome of 190 consecutive cycles induced by human menopausal gonadotropin/human chorionic gonadotropin in the program of IVF at Norfolk is compared with contemporary studies of pregnancy outcome in normal reproduction. The in vitro data indicate that the Norfolk program has recorded no menstrual abortions, a 33% preclinical and clinical abortion rate, and a viable pregnancy rate that approaches but does not equal the term delivery rate of normal reproduction. However, these results have been achieved by the transfer of multiple concepti, whereas normal reproduction depends on the fertilization of a single oocyte.

The importance of the follicular phase to success and failure in in vitro fertilization.

One hundred seventy-five cycles in patients with irreparable tubal disease were stimulated by human menopausal gonadotropin/human chorionic gonadotropin for the purpose of in vitro fertilization. As judged by the height of the peripheral estradiol response, the patients were classified as high, intermediate, or low responders. In addition, the estradiol pattern of the response was found to be separable into six categories. The pregnancy rate was found to be related to the height and to the pattern of peripheral response. The overall pregnancy rate in this consecutive series was 19% but varied according to the height and pattern of response from 40% to 0%.

Serum levels of steroid and placental protein hormones in ectopic pregnancy.

UNLABELLED: The hormonal profiles of extra-uterine pregnancies (EP) were compared with the normal intra-uterine pregnancies (IUP), and threatened abortions (TA) of good outcome. In 45 cases of EP confirmed histologically, maternal serum human chorionic gonadotropin (hCG), pregnancy specific beta 1-glycoprotein (SP1), 17 beta-estradiol (E2) and progesterone (P) were measured serially before treatment by enzyme immunoassays (EIA). The same hormones were also determined in the control groups, 26 with normal IUP and 24 with TA. All four hormone levels in EP were significantly lower (P less than 0.01-P less than 0.0001) than in normal pregnancies and threatened abortions of matched gestational age except the hCG and E2 in the fifth week of pregnancy. The mean values of E2 and P were found in the normal levels of luteal phase or slightly over them (8th-9th and 9th-10th weeks, respectively). No increase in the hormonal profiles of the above two steroids was noticed between 5 and 10 weeks' gestation in EP. IN CONCLUSION: (a) The significantly lower values of hCG and SP1 in EP were confirmed; (b) the serial and concurrent hormonal measurements assure the verification of EP and the differentiation from normal IUP and TA of good outcome; (c) the ectopic implantation of trophoblast critically reduces its vitability to hCG and SP1 synthesis and it can only partially compensate for the reduction of corpus luteum function.

Tumour-associated antigens, CEA, CA 125 and SCC in serum and follicular fluid of stimulated and unstimulated cycles.

Serum and follicular fluid levels of CEA, CA 125 and SCC of women participating in an IVF program, in 42 cycles stimulated with GnRH-a and gonadotropins and in 26 unstimulated cycles triggered with HCG, were evaluated and compared with (a) steroid and gonadotropin levels, (b) the results of IVF, and (c) serum values in a control group of women with spontaneous normal ovulatory cycles. In the control group, serum antigens did not vary significantly during the 3 phases of the cycle. In stimulated cycles the median values in serum were 0.7 ng/ml (range, 0.0-2.1) for CEA, 14.0 U/ml (3.3-32.4) for CA 125 and 2.05 ng/ml (1.1-17.8) for SCC, whereas the median values in follicular fluid were 0.6 (0.0-27.9), 21.5 (0-670) and 21.4 (1-360), respectively. In unstimulated cycles the median values and ranges in serum were 0.9 (0.4-3.9), 12.1 (4.8-63.4) and 1.85 (0.7-4.4), respectively, whereas in follicular fluid they were 2.9 (0.4-180.7), 32 (1.7-600) and 231 (10.8-904). Different follicles of the same patients in stimulated cycles showed a wide divergence for all three antigens. In unstimulated cycles all three antigens in follicular fluid were strongly-correlated and a significant inverse correlation was observed between LH and both CA 125 and SCC in serum. In either group of cycles, no significant relationship was found between any serum or follicular fluid antigen and estradiol or testosterone, pregnancy rate, or oocyte quality and fertilization.(ABSTRACT TRUNCATED AT 250 WORDS)

Immune dysfunction in patients with unexplained repeated abortions.

OBJECTIVES: To examine the immunological profiles by antiphospholipid antibodies IgG, IgM, IgA immunoglobulins ACA, as well as C3, C4 complement component levels. METHODS: A group of 44 women with a history of three or more consecutive pregnancy losses was compared with 34 normal women. RESULTS: Our results showed lower levels of IgG immunoglobulins for the patient group (P < 0.001) while the C3, C4 complement component levels remained unaltered. Anticardiolipin antibodies were positive in ten patients for IgG or IgM isotypes or for both presenting a prevalence of 22.7% while none of the control subjects had ACA positive titers. The lupus anticoagulant was not detected in either group. Ten patients (22.7%) presented positive autoantibody tests as compared with only 3 (8.8%) of the control group. No statistical differences were found between the two groups when the frequency of each autoantibody's positive tests were examined separately. CONCLUSIONS: An inconsistent immune derangement seems to be present in recurrent aborters with the presence of anticardiolipin antibodies as the stronger representative marker of immune alteration.

Review of ovarian cancer of the University of Athens.

One hundred and eight patients with cancer of the ovaries were studied retrospectively for a period of seventeen years. All the patients were managed in the Second Department of Obstetrics and Gynecology of the University of Athens. The symptoms of the patients were: pelvic pain in 43, ascites in 27, metrorrhagia in 23 and weight loss in 12. Fifty six per cent of the patients were between 40 to 60 years old and 63% were menopause. The PAP-smear in 40% was class I or II, in 50% was class III and in 10% was class IV-V. The stage of the disease was: 3 patients stage I, stage II 38, stage III 42 and 25 stage IV. No patient had stage 0. Laparotomy was done in all the patients. Thirty eight patients had Co-treatment and 42 patients chemotherapy. The pathology report was: serous cystadeno-Ca in 40, mucinous cystadeno-Ca in 38 of the cases, adenocarcinoma 18 and 12 other types of malignant tumors. The follow up of the patients showed a five years survival rate in 10% for stage I, 25% for stage II, 5% for stage III and none for stage IV.

Pregnancy after in vitro fertilization in a patient with borderline tumor of the ovary.

A 36 year old woman with unilateral tubal disease was found, during infertility evaluation, to have epithelial tumor of borderline malignancy in one ovary. She was treated with salpingo-oophorectomy and three months later she asked to participate in our IVF program. High doses of gonadotropins were given for controlled hyperstimulation and a successful pregnancy and live birth was achieved.

Primary adenocarcinoma of the fallopian tube with tuberculosis (short communication).

A case of primary adenocarcinoma and tuberculosis of the Fallopian tube is presented. The clinical symptoms of the patient were pelvic pain and primary infertility. The gynecologic examination revealed a palpable tubal mass and the diagnosis was performed from the laparotomy and the pathology report.

Heterotopic pregnancies in an in-vitro fertilization program.

During a four-year period in vitro fertilization (IVF) was carried out in 2,356 cycles. The pregnancy rate per transfer was 24% while the incidence of ectopic pregnancies was 7.5% per pregnancy. There were seven cases of heterotopic pregnancies-simultaneous intra- and extrauterine pregnancies (1.5% among all IVF pregnancies). Two of them were diagnosed after tubal rupture of the ectopic pregnancy and five cases were diagnosed by ultrasound at the 7th or 8th week of gestation. Laparotomy and subsequent salpingectomy was carried out in six cases while in one case the ectopic pregnancy was removed by laparoscopy. Three out of the seven heterotopic pregnancies (43%) were successfully continued with normal intrauterine embryo development and delivery.

Plasma and amniotic fluid concentration of fibronectin during normal and diabetic pregnancy.

Fibronectin is a plasma glycoprotein which is involved in coagulation, platelet function, tissue repair and the vascular endothelial basement membrane. To ascertain the influence of pregnancy on plasma concentrations of fibronectin, we qualified plasma concentrations of fibronectin in normal pregnant women during the first, second and third trimester; at the time of delivery; and on the third day post partum, using a radial immunodiffusion plate procedure. The concentrations of fibronectin found in these samples were compared with the concentration of fibronectin in 20 pregnancies complicated by diabetes. Mean plasma concentrations of fibronectin rose significantly through pregnancy and were significantly higher during delivery. A decrease in the concentrations was noticed on the third post partum day. An even more significant decrease of maternal plasma concentrations was noticed during cesarean section in normal pregnancies as compared to the concentrations found at the time of normal delivery. Of the diabetic group of women studied, higher concentrations of plasma fibronectin were found at the time of cesarean section than at the time of delivery. Maternal plasma concentrations of fibronectin were significantly greater than amniotic fluid and umbilical cord plasma concentrations.

Peritoneal fluid volume parameters in infertile patients.

The peritoneal fluid volume (PFV) and its cellular and acellular components have been repeatedly associated with infertility. The PFV from 88 infertile women was analyzed in relation to endometriosis, pelvic adhesions, tubal patency, luteinization, endometrial cells and macrophages. The independent existence of parameters such as the onset of luteinization, the increased population of macrophages and the presence of endometriosis increase statistically significantly the PFV. In the presence of peritoneal adhesions or/and obstructed tubes the PFV was significantly decreased.