Arginine vasopressin in human follicular fluid.

Arginine vasopressin (AVP) was determined in plasma and follicular fluid in 28 women in an in vitro fertilization program. In 23 women, follicular fluid was collected by laparoscopy during general anesthesia, and in 5 women, it was collected transvaginally with no such anesthesia. Plasma AVP increased markedly from its basal (preanesthesia) value in the first group, whereas it did not change in the second group. AVP concentrations were approximately 10-fold lower in the follicular fluid than in the plasma collected simultaneously in the anesthetized women. AVP levels were not significantly different in plasma and follicular fluid in the women of the second group. AVP concentrations were similar in ovarian venous and brachial venous plasma in 4 women during surgery. These results indicate that AVP concentrations in follicular fluid are equal to or lower than those in plasma and that AVP concentrations are not higher in efferent blood from the ovary than in peripheral blood.

Correlation between follicular fluid content and the results of in vitro fertilization and embryo transfer. II. Inhibin and aromatase inhibitor activity.

The inhibin content and aromatase inhibitor activity (AIA) of 72 follicular fluids (FF) obtained from 42 women undergoing in vitro fertilization (IVF) and embryo transfer (ET) were studied as a function of IVF ET outcome. Inhibin levels were determined by bioassay (BA) and RIA; AIA was measured by BA. The inhibin content of follicles characterized as immature by their estradiol (E2) levels and E2/progesterone (P) ratios was significantly lower (P less than 0.05) than that of mature follicles (i.e. leading to pregnancy). The mean AIA for mature follicles were significantly lower than AIA in groups where pregnancy was not obtained. AIA for follicles from which a pregnancy was obtained for each ET was also significantly lower than that in FF characterized as immature of hypermature. The highest E2/AIA and inhibin BA/AIA ratios were associated with the highest incidence of successful IVF ET outcome. No correlation was found between AIA and inhibin, on the one hand, and E2, delta 4-androstenedione, E2/P, and PRL, on the other. However, a positive correlation was found between inhibin (RIA and BA) and P, reflecting the production of inhibin by granulosa cells during luteinization. These studies allowed us to conclude that FF inhibin levels do not differ according to IVF ET outcome, but are an index of follicular maturation. AIA not only constitutes an index of follicular maturation and granulosa cell luteinization, but is of predictive value for IVF ET outcome as E2/AIA and inhibin BA/AIA ratios.

Microhysteroscopy: a new approach to the diagnosis of cervical intraepithelial neoplasia.

The recent development of the microhysteroscope permits observation of female genital tract surfaces at different magnifications ranging from 1:1 to contact microscopic examination of vitally stained living cells at a magnification of 150:1. One of the emerging applications of the microhysteroscope is in the diagnosis of cervical intraepithelial neoplasia (CIN). To evaluate the capabilities and reliability of microhysteroscopy, two studies were performed. The first study compared this technique with colposcopy, cytology, and histology in the evaluation of 92 patients with abnormal Papanicolaou smears (CIN II, III). The second study prospectively evaluated 800 patients using microhysteroscopy as a screening tool. Initial results of the two studies suggest that microhysteroscopy is a highly precise method of evaluating cervical precancerous lesions.

Diagnosis and treatment of intrauterine adhesions by microhysteroscopy.

In this report of 69 patients, a new type of hysteroscope was used to evaluate the extent and character of intrauterine adhesions, to perform lysis of them, and to monitor the effects of therapy. Additionally, prospective studies with regard to pathogenesis and endometrial regeneration can be achieved in vivo. In 59 patients the procedures were performed in an office setting using a CO2 hysteroscopic technique without the need for local anesthesia or cervical dilatation. Of 30 infertile patients, 38% subsequently had uncomplicated deliveries. The severe forms of this disease still remain very difficult to treat effectively. When the adhesions were severe or the procedure painful, the operation was scheduled under general anesthesia (ten cases). A sequential hysteroscopy with good patient acceptance affords additional opportunity for removing residual adhesions and intrauterine devices, and serves as a basis for ending treatment with steroids.

Comparison of growth hormone responses to growth hormone-releasing factor and clonidine in women with normal or poor ovarian response to gonadotropin stimulation.

OBJECTIVE: To assess the reliability of growth hormone (GH) secretion tests using provocative agents in women of different ovarian status. DESIGN: Comparison of GH secretion in response to clonidine (Catapressan; Boehringer Ingelheim, Reims, France) and growth hormone-releasing factor (GH-RF). SETTING: University Hospital, Hôpital Tenon, Paris, France. PATIENTS: Women categorized as "normal" (n = 6) or "poor" responder (n = 7) to ovarian stimulation with gonadotropins, depending on the follicular development attained at previous IVF attempts. INTERVENTIONS: Clonidine (0.300 mg administered orally) once and GH-RF (1 micrograms/kg IV) repeated twice. The tests were performed in random order in each individual on following cycles. MAIN OUTCOME MEASURES: Basal and peak GH values, area under the curve (AUC). RESULTS: Poor responder patients show significantly higher basal levels of FSH, GH, and insulin-like growth factor 1; FSH and basal GH levels are positively correlated. Peak GH levels and AUC are not significantly different in both categories of patients, whether GH-releasing factor or clonidine are used as provocative agents. True positive rate is 56.4% at the cutoff value of 7 micrograms/L, with no significant difference between the patients of the normally or poorly responding groups. At the 10-micrograms/L cutoff level, the true positive rate is almost half in the poor responder group (19.0% versus 38.9%), but the difference is not significant. CONCLUSIONS: These results raise concern about using the GH secretory response to a single clonidine administration as a predictive test of the therapeutic benefit that could be obtained by co-stimulating the somatotropic axis during a treatment with gonadotropins in poor responder patients, especially when their FSH basal levels are elevated.

Pregnancies after replacement of frozen-thawed embryos in a donation program.

Eighteen patients with primary (n = 8) or secondary (n = 10) ovarian failure were enrolled in a donation program. In 15 cases, the oocytes were donated anonymously; in 3 cases, they were donated by the sister of the recipient. All the recipients had cyclic steroid replacement therapy that included estrogens and progesterone administered by the transdermal and tranvaginal routes, respectively. The embryos obtained were cryopreserved and replaced with no attempt at synchronization between donor and recipient. Steroid hormonal patterns were within the range for the normal menstrual cycle and endometrial biopsies taken on day 21 or 22 of the treatment cycles were independently assessed as being representative of day 21 +/- 2. Four of 12 transfers were successful (31%): 1 patient aborted at 6 weeks, and the three others were delivered, one normally and two by cesarian sections. The authors' practice suggests the following: (1) steroid supplementation by transdermal and transvaginal routes is effective, (2) synchronization between donor and recipient is no longer required with the use of frozen-thawed embryos, and (3) the "temporal window" is large since all the replacements were done on day 14 of the cycle.

Mature and immature oocytes in large and medium follicles after clomiphene citrate and human menopausal gonadotropin stimulation without human chorionic gonadotropin.

After ovarian stimulation with clomiphene citrate combined with human menopausal gonadotropin, 24 large (greater than 16 mm) and 16 medium (7 to 15 mm) human follicles were classified according to plasmatic estradiol (E2), luteinizing hormone (LH), and histology of the follicle and oocytes (in thin sections). An asynchronism of several hours between the stage of development of the largest and large cohort follicles is observed; overripeness of oocyte cumulus complex (OCC) is revealed. An asynchronous response to gonadotropins in granulosa and cumulus is also seen in the cohort of medium follicles of the same ovary, but not resumption of nuclear maturation of the oocyte. The efficiency of these oocytes after fertilization is discussed.

Hormonal secretions in singleton pregnancies arising from the implantation of fresh or frozen embryos after oocyte donation in women with ovarian failure.

OBJECTIVE: To determine whether levels of human chorionic gonadotropin (hCG), 17 beta-estradiol (E2), and progesterone (P) are different in the peri-implantation phase of fresh versus frozen embryos. DESIGN: Hormonal secretions were measured on days 9 and 11 after implantation and at 4, 5, and 6 weeks gestation. PATIENTS: Thirty-one pregnancies were achieved in 65 patients with ovarian failure. Seventeen singleton pregnancies developed after implantation of 4 frozen and 13 fresh embryos. RESULTS: Human chorionic gonadotropin and E2, contrary to P, were higher in cases of fresh embryos from the 9th day after transfer to the 5th week at which time they become statistically significant (respectively, for hCG and E2, 5,800.3 +/- 332.3 versus 2,027.3 +/- 916.3 [mean +/- SD] mIU/mL for hCG and 562.3 +/- 215 versus 291 +/- 152 pg/mL for E2). CONCLUSIONS: This difference might be explained by either the higher number of fresh embryo replaced or by the fact that the number of blastomeres and also their metabolic activity could be reduced after freezing and thawing.

Timing of nuclear maturation and cumulus dissociation in human oocytes stimulated with clomiphene citrate, human menopausal gonadotropin, and human chorionic gonadotropin.

The maturation of the preovulatory human follicle larger than 16 mm is described between 0 and 36 hours after human chorionic gonadotropin (hCG) administration. The nuclear evolution of the oocyte is timed: prophase at 14 hours, germinal vesicle breakdown at 15 hours, metaphase I at 20 hours; metaphase II is complete by 35 hours. The quantified expansion of the cumulus is related to nuclear evolution. Almost complete expansion may already be observed 18 hours before ovulation (20 hours after hCG). The specific action of clomiphene citrate, human menopausal gonadotropin, and hCG stimulation on the granulosa induces a more rapid luteinization than is found after other means of stimulation or in spontaneous cycles. Oocytes from follicles less than or equal to 16 mm on preovulatory ovaries often show a reaction to hCG that may be related to their subsequent quality.

A multiparametric analysis of endometrial estrogen and progesterone receptors after the postovulatory administration of mifepristone.

A double-blind randomized study was performed in two groups of eight normally cycling patients: group I received 10 mg/d of RU486 for 4 days from the date of ovulation and group II received a placebo. On day +5, cytosol and endometrial estrogen receptors (ERs), and progesterone receptors (PRs) were analyzed by radioligand binding assay as well as by enzyme immunochemistry. Histologic studies showed that all the endometria of group I were abnormal (luteal insufficiency and/or E/P imbalance). The nuclear PR levels were significantly higher in group I (843 +/- 422 fmol/mg) deoxyribonucleic (DNA) compared with 482 +/- 232 fmol/mg DNA in group II. Immunohistochemical study showed that ER and PR staining was higher for both glands and stroma in group I (52% and 72% for the respective receptors), compared with the receptor-immunostained surface observed in group II, which was reduced to 40% for ER and to 4% for PR. This study demonstrates that RU486 administered in the immediate postovulatory period blocks normal tissue evolution in the follicular phase as well as the processing of PR.

Multiple pregnancies: the price to pay.

Since 1980, the rate of multiple pregnancies due to assisted reproductive technology has been multiplied by 10, especially for twin pregnancies and for cases involving simple stimulation of ovulation. The prices paid are: an increase in prematurity (82% of deliveries); perinatal mortality (an increase of 74%); and transfer to intensive care units (95% of infants born of multiple pregnancies). This does not take into account the rise in cost per child, which increased by 1.9 for twins and 3.7 for triplets. The solution does not lie in selective embryo reduction but in the reduction of the number of embryos transferred.

Lone hyperuricemia during pregnancy: maternal and fetal outcomes.

OBJECTIVE: Study of maternal and fetal consequences of lone hyperuricemia during pregnancy and demonstration that lone hyperuricemia is not a risk factor regarding the onset of preeclampsia. STUDY DESIGN: Retrospective study of two groups of women, one found to have lone hyperuricemia during pregnancy (n=102) and the others with normal serum uric acid levels (n=100). RESULTS: The only consequence identified of the lone hyperuricemia was a lower birth weight of children born to mothers found to have lone hyperuricemia for more than 2 weeks (P<0.05). CONCLUSIONS: Lone hyperuricemia is not a risk factor regarding the onset of preeclampsia. It is therefore unnecessary to measure serum uric acid level during a normal pregnancy.

First line immunochemotherapy with cisplatin-based protocol by intraperitoneal and intravenous routes in ovarian cancer: technique and results of 82 cases.

OBJECTIVES: The aim of this study, initiated in 1982, was to determine the feasibility and the interest of a first-line immunochemotherapy delivered by intraperitoneal (i.p.) and intravenous (i.v.) routes combined in ovarian cancer. STUDY DESIGN: Eighty-two naive patients with a common epithelial cancer entered the study from January 1982 to December 1990 (median follow up > 70 months). For i.p. infusion, we used a simple lumbar puncture needle left in situ for < 2 h. The first 18 patients received monthly by i.p. route: Adriamycin (DXR) 40 mg/m2, Fluorouracil 1000 mg/m2, Cisplatin (CDDP) 90 mg/m2, Bleomycin 30 mg -DGZ (extract of vibrio cholerae) 60 mg/m2. For the remaining 64 patients Aracytin 500 mg/m2 replaced DXR and the dose of CDDP was more than doubled (200 mg/m2) thanks to the use of sodium thiosulfate. All 82 patients received Ifosfamid 1300 mg/m2 intravenously. RESULTS: Local toxicity consisted in one subcutaneous abscess and one bacterial peritonitis out of 1508 abdominal punctures. Stage III turned out to be the most interesting group to evaluate the efficacy of a first-line protocol. In this group 34 out of 47 patients (72.3%) who underwent an initial incomplete surgery were in complete remission (CR) at second-look. Nevertheless, 21 out of the 34 patients in CR relapsed (61.7%) and 14 died (43.2%). CONCLUSION: These results show the efficacy of our regimen administered i.p., and the safety of the delivery by a simple needle which avoids the complications of the implantable systems. Nevertheless, the usefulness of a systematic second-line chemotherapy (Paclitaxel?), despite a prognosis situation as favourable as a CR at second-look, must be taken into consideration.

[Breast cancer during pregnancy]. / Cancer du sein au cours de la grossesse.

Breast cancer during pregnancy is a rare eventuality. The mean age of women is 34 years. The same histological types (essentially ductal) are found, but there are more inflammatory forms and/or node involvement and general metastasis. The hormonal receptors are usually negative. The clinical diagnosis is often difficult and delayed. The mammography is perturbed because of breast congestion, giving reason for histological verification. The treatment must consider the fetus as much as possible. The traditional mastectomy associated to axillary nodes dissection is replaced most of the time by a large tumorectomy with axillary node dissection with the condition not to delay the complementary radiotherapy fore more than three months and to take in consideration the toxicity in relation to the gestational age, the site of impact and the doses given. Also, chemotherapy, if indicated, must begin in the month following the diagnosis. The pronostic is not as good in general as that in the non pregnant woman, because of the delayed diagnosis, the ganglionic metastasis, and the aggravation of the forms accelerated by pregnancy. The prevention consists of a clinical examination of the breast early in pregnancy (particularly after 30 years) and by histologic verification in cases where there is the slightest doubt.

[Role of microbiopsies in the therapeutic and diagnostic approach in cases of mammary microcalcification: preliminary results]. / Place des microbiopsies dans la stratégie diagnostique et thérapeutique à l'égard des microcalcifications mammaires: résultats préliminaires.

The increase of mammographies has lead to the discovery of more frequent mammary microcalcifications. Presently, about 30% of breast tumors are discovered from infraclinics lesions. Instead of the different classifications, the microcalcifications are the omnious sign with bad specificity. It is in the aim to improve the diagnostic etiology and the choice of therapy, that the directed microbiopsies on microcalcifications had been realized. After an orthogonal location and under local anesthesia, we performed at least six biopsies with a 2.1 mm (14 gauge) needle. This allowed recovery of malignant lesions during the control of microcalcifications and permitted considerable early operative treatment. In fact, a diagnostic and therapeutic advancement of 12 months as compared to a clinical diagnosis, permitting a 30% reduction of metastasis.

[Therapeutic management of ovarian dystrophy and insufficiency in abortion disorders: recent data]. / Prise en charge thérapeutique de la dystrophie et de l'insuffisance ovarienne débutante dans la maladie abortive: données récentes.

Many reports suggested that the high rate of miscarriage in women with polycystic ovaries may be due to increased urine and/or plasma LH concentration. In fact, with the exception of pulsatile GnRH, any treatment likely to increase the plasma LH level results in unchanged or rather low miscarriage rates. Conversely, a reduction in this rate by GnRH agonists is not conclusive. Excess weight may also increase the risk of miscarriage. In women with incipient ovarian failure, the miscarriage rate is mainly linked to age. No stimulation has been found to be effective in these patients. There is a need for more extensive evaluation in GnRH analog microdoses, recombinant FSH and GnRH antagonists. Oocyte donations from younger women are difficult to obtain because of the lack of donors in France.

[The plasma and urinary hormone profiles during treatment with human gonadotrophins (author's transl)]. / Profils hormonaux plasmatiques et urinaires au cours des traitements par les gonadotrophines humaines.

This study presents 6 cases of sterility that had anovulation or disturbances of ovulation treated by HMG HCG. Induction of ovulation was monitored by daily urinary oestrogen assays. The parallel study of the plasma profiles of oestradiol 17 beta, of FSH, and of LH obtained during the induction of ovulation show that the cycles in induced ovulation are not physiological in character. On comparison of the plasma profiles with the urinary profiles a significance delay is shown in the urinary oestrogen profile as compared with the plasma one and explains to a certain extent the results that were obtained.

[Ovarian cancer and pregnancy. Circumstances of detection, treatment, etiologic and prognostic diagnosis]. / Cancer de l'ovaire et grossesse. Circonstances de découverte, traitement, diagnostic étiologique et pronostic.

Prognosis of ovarian cancer is usually very serious. In young women whether pregnant or not, some points have to be emphasized: --Histological types with a more favorable prognosis (mucinous, seminomes, border-line) as well as those lower grades, are more frequent in younger women; conservative surgery is indicated in case of strict unilateral localization. --During pregnancy, acute symptoms, frequent routine clinical examinations as well as repeated ultrasonography, allow an earlier diagnosis. --The fetal prognosis is always very serious, especially during the first trimester, the maternal prognosis stays the same, whether the women is pregnant or not. --The two personal clinical reports on pregnancy associated to ovarian cancer, treated and cured with a follow up of respectively 7 and 10 years, do confirm our statement.

[Simultaneous registration of fetal cardiac rhythm of twins during labor]. / Enregistrement simultané du rythme cardiaque foetal des deux jumeaux pendant le travail.

This technical note: Describes a new apparatus which allows both fetuses to be monitored at the same time in a twin pregnancy in labour. The principle by which the signals are separated and a calculation of how the two tracings of the fetal heart rates are obtained is analysed.

[An analysis of 65 cases of salpingostomy carried out using microsurgical techniques (author's transl)]. / Analyse de 65 salpingostomies microchirurgicales.

65 salpingostomies were carried out using microsurgical techniques between 1976 and 1978. The patency rate was 89 p. 100. There were 30 p. 100 intra-uterine pregnancies and 4 p. 100 ectopic pregnancies. The authors emphasize the prognosis that can be obtained from hysterosalpingography, laparoscopy and histological examination of the tissues and the very poor results that are obtained even using these methods when a second operation is undertaken.