Biomedical subjects
Publications and source records attributed to J M Antoine.
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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.
The selective reduction of embryos in multiple pregnancies poses numerous medical, technical, ethical and psycho-social problems. In a retrospective study, we analysed nine hundred and twenty-two pregnancies obtained using medically assisted procreation between May 1982 and May 1990. Among 922 successful pregnancies, 372 were singleton, 102 were twin and 13 were triplet. Data from this analysis and from a French multicentre study of 262 embryo reduction procedures demonstrated the value of an embryo quality score for minimizing the risk of multiple pregnancy and the existence of extremely infrequent, ethically acceptable indications for embryo reduction. These indications included ultrasound-proven malformations of one fetus, multiple pregnancies in patients with extensive uterine scarring, and multiple pregnancy despite the appropriate use of preventative measures which can be expected to make this technique unnecessary in the future.
Of 44 pregnancies obtained at the Tenon Maternity Hospital by in vitro fertilization (IVF) using donated oocytes, 25 have already been completed by spontaneous delivery or cesarean section: 22 (88%) single; 2 (8%) twins, and 1 (4%) triple. The most frequently seen complications of pregnancy were hypertension (16%) and preterm labor in the last 3 months (12%). However, as compared to a control group of 275 pregnancies resulting from classical IVF, the only difference was a very high percentage of cesarean sections (72%). No fetal deaths or neonatal malformations were reported.
We retrospectively analyzed the prevalence and prognostic significance of plasma progesterone rises during in vitro fertilization (IVF) protocols including pituitary down-regulation by LHRH agonists in a long protocol and stimulation by hMG (n = 1,116: Group A) or pure FSH (n = 178: Group B). On the day of hCG injection, plasma progesterone level was in the 0.60-0.99 ng/ml range in 7.1% of group A patients and 6.2% of group B patients (NS) and above 1 ng/ml in respectively 4.0% and 3.4% of the cases (NS). On the same day, plasma progesterone was strongly correlated with plasma estradiol (r = 0.26 - p < 0.001 in group A; r = 0.21 - p < 0.01 in group B). However, increased progesterone levels were not associated with changes in plasma LH levels, falls in plasma estradiol levels after hCG injection, or significant modifications in biological and clinical results of IVF. The cause of this pattern of progesterone rise remains to be elucidated.
In the present study we evaluated lactose malabsorption (LM) after ingestion of three dairy products in 53 healthy institutionalized elderly people. A preliminary screening with milk (250 ml, 11 g lactose) was carried out to select the LM subjects using the H2 breath test. The effect of consuming an equivalent amount of lactose contained in yogurt and fermented-then-pasteurized milk (FPM) was then assessed in LM subjects. Results indicated that 36% of the elderly population studied was considered as LM and that breath H2 excretion was significantly higher after ingestion of milk than after ingestion of yogurt. This beneficial effect was partially eliminated when FPM was tested. Moreover, breath H2 excretion was significantly higher (p less than 0.05) 3 hours after ingestion of FPM compared to the normal yogurt. These results demonstrate a high prevalence of LM in the elderly and confirm the positive effect of yogurt on lactose absorption, whereas pasteurized yogurt did not cause the same effect.
A hundred and twenty three patients with intraperitoneal cancer (mostly ovarian) were treated between 1980 and 1990 with intraperitoneal chemotherapy administered through a "needle". Local complications were infinitely fewer and less serious than those observed with materials implanted for months. General complications depended on which protocols were being used. But tolerance on the whole was better when the drugs were administered intraperitoneally. This is particularly clear with cisplatin, although the dose is doubled intraperitoneally over a period of 10 months instead of 6. In this ways there was hardly any neurotoxicity and there was a noteworthy prolongation of survival time in cases of ovarian carcinoma.
Between January 1980 and February 1988, 61 women with ordinary ovarian carcinoma (OC) were treated with combined intraperitoneal and intravenous first-line therapy. For intraperitoneal infusions we did not use implanted systems which are often poorly tolerated and sometimes create non-negligible complications. We simply used a lumbar puncture needle left in situ for less than 2 hours. In second regard laparotomies, the 7 patients with stage I OC and the 3 patients with stage II OC were in histologically and cytologically proven complete remission, as were 34 of the 43 patients with stage III OC (79 percent) and 1 of the 8 patients with stage IV OC. After a mean follow-up of 56 months, the overall actuarial survival rate was 66 percent and the survival rate without recurrence was 54 percent. During the same period, 26 patients with recurrent OC were treated with second-line intraperitoneal chemotherapy. After a mean follow-up of 30 months, 10 were in apparently complete remission, and after a 27 to 61 months period 7 of these 10 patients had no recurrence. These results must be compared with those obtained with other salvage methods.
The relationships between essential fatty acid (EFA) composition of colostrum and white adipose tissue (WAT) were examined on day 5 after delivery in 69 healthy women. Fatty acid composition was assessed by capillary gas chromatography, and 33 fatty acids were detected in colostrum and in WAT. Total polyunsaturated fatty acid (PUFA) content was similar in colostrum and in WAT (15.7 +/- 3.1% and 16.1 +/- 3.8%, respectively), but long-chain PUFA content was higher in colostrum than in WAT (2.9 +/- 0.6% and 1 +/- 0.2%, respectively; P less than 0.001). The concentrations of linoleic acid were significantly correlated between colostrum and WAT (r = 0.77, P less than 0.0001). No correlation was found for alpha-linolenic acid. The relationships between long-chain PUFA composition of colostrum and WAT suggested that individual factors along with tissue specificity of the mammary gland are involved in either the capacity of desaturating and chain-elongating pathways and/or incorporation of long-chain PUFAs into colostrum.
Lactose in yogurt with live bacteria is better tolerated than lactose in other dairy foods, partly because of the activity of microbial beta-galactosidase (beta-gal), which digests lactose in vivo. To evaluate the ability of different strains and species of lactic acid bacteria to digest lactose in vivo, yogurts (containing mixtures of strains of Streptococcus salivarius subsp thermophilus and Lactobacillus delbrueckii subsp bulgaricus) and fermented milks (containing individual species of S thermophilus, L bulgaricus, L acidophilus, or Bifidobacterium bifidus) that varied in microbial beta-gal activity were produced. Selected products were fed to healthy people who cannot digest lactose, and breath hydrogen production was monitored. All yogurts dramatically and similarly improved lactose digestion, regardless of their total or specific beta-gal activity. The response to fermented milks varied from marginal improvement with B bifidus milk to nearly complete lactose digestion with L bulgaricus milk. The results suggest that total beta-gal was not the limiting factor in promoting lactose digestion, perhaps because of a limited rate of intracellular substrate transport.
Plasma and follicular fluid (FF) hormone assays for follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), oestradiol (E2), progesterone (P), delta-4-androstenedione (A4) and testosterone (T) were performed on the day of oocyte retrieval in two groups of normo-ovulatory women enrolled in an in-vitro fertilization (IVF) programme: 24 were treated using the decapeptyl agonists DTRP6, of luteinizing hormone-releasing hormone (LHRH) in the long protocol associated with human menopausal gonadotrophin (HMG) (49 FF) and 14 were stimulated with HMG alone (33 FF). In both FF and plasma the mean concentration of P was greater, and the E2/P ratios as well as the LH levels were lower in the agonist-treated group. In this group the follicular concentration of P was greater and the E2/P ratio lower when pregnancy occurred following IVF. The hormonal modifications may be due to greater functional maturity of the granulosa cells.
A case of Eisenmenger syndrome associated with an ongoing pregnancy and maternal death one month after cesarean section is reported. The review of the world literature shows the very high maternal risk of this condition, which should be prevented by tubal sterilization or therapeutic abortion in the very early pregnancy.
Clinical hyperstimulation is the most serious complication of ovulation induction, occurring in approximately 3% of cases (0.8% in the severe form). Paradoxically, it seems to be rare following in vitro fertilization, probably because all the follicles are aspirated. High-risk patients are those with polycystic ovarian disease, hyperprolactinaemia and hypothyroidism. All forms of ovulation induction have been implicated. Use of LHRH agonists have not reduced the incidence of hyperstimulation and they may even have increased it. An ongoing pregnancy seems to predispose to the occurrence of hyperstimulation, due to the secretion of hCG. Clinically, three stages of hyperstimulation have been described by the WHO (mild, moderate and severe). The pathophysiology is not completely understood, although prostaglandins, histamines and, especially, the ovarian renin-angiotensin system may be involved. Local ovarian complications and thromboembolic complications have also occurred. The treatment of severe hyperstimulation is both symptomatic (fluid replacement, aspiration of effusions, moderate sodium and water restriction, small doses of diuretics) and specific (corticosteroids, aspiration of ovarian cysts, even voluntary interruption of pregnancy in the most serious forms). If the hyperstimulation occurs in the absence of pregnancy, antihistamines or antiprostaglandins can be given. Prevention is exceedingly important. This can be helped by recognition of polycystic ovarian disease and stimulation of these cases by clomiphene citrate or pure FSH associated, for use in in vitro fertilization, with prolonged desensitization using LHRH agonists. Daily ultrasound and hormonal monitoring of ovulation induction is required. When there is excessive response to stimulation, it is prudent not to induce ovulation with hCG or, alternatively, to aspirate all the follicles and freeze the embryos obtained without giving further injections of hCG in the luteal phase. Clinical ovarian hyperstimulation is the classic form of iatrogenic disorder and is the most important complication of ovulation induction treatments, since it can be life-threatening in its most severe form. In this chapter we review current knowledge concerning the frequency, factors associated with its occurrence, clinical aspects, physiopathological mechanisms and, finally, the possibilities for treatment and prevention.
In 33 patients treated with a combination of an LHRH agonist (LHRH-A) and gonadotrophin in a long protocol, a biological hyperstimulation occurred (E2 greater than 2500 pg/ml on the day of HCG administration and 4722 +/- 1190 pg/ml the day after, with greater than 10 follicles greater than 12 mm on each ovary). The replacement of fresh embryos were deferred and LHRH-A was continued, and an endometrial biopsy was performed on the theoretical day of replacement (2 days after oocyte recovery). With this technique, we obtained a mean number of 17.9 +/- 7 oocytes, a fertilization rate of 49% and a replacement rate of 87% in a deferred cycles. The overall pregnancy rate of frozen-thawed embryos was 27% in the seven spontaneous cycles, 12 induced cycles and 10 artificial cycles. Only one severe hyperstimulation occurred and this case emphasizes that caution remains necessary even with this technique.
Between February 1987 and February 1989, 13 women with primary ovarian failure due to gonadal dysgenesis were treated with embryo transfer following ovum donation in 22 cycles. Eight pregnancies were obtained (36.7% per transfer); four births of normal children, two spontaneous abortions and two other pregnancies currently ongoing (between 5 and 8 months). An association of percutaneous oestradiol, oestradiol valenate and intravaginal progesterone was used as hormone substitution and embryo transfer was only performed following assessment of the endometrium during a previous cycle. Apart from the day of embryo transfer, which was the same for all patients (the 2nd day after initiation of progesterone) various prognostic factors were analysed. These were the type of gonadal dysgenesis (45 XO, 46 XX or 46 XY), the number of embryos replaced, whether they had been frozen, whether the egg donor was anonymous and finally the influence of the hormone substitution protocol. Only the number of embryos replaced and the substitution protocol seemed to influence the implantation rate. The other parameters, and in particular the type of gonadal dysgenesis, seemed to have no effect on the results. The pregnancy rate per transfer was 30% for 45 XO (10 transfers), 25% for 46 XX (eight transfers) and 75% for 46 XY (four transfers).
In order to evaluate the exact role of GnRH agonists, we have undertaken a randomized prospective study comparing two groups of 90 normo-ovulatory patients, aged less than 38 years and with tubal infertility with no male factor. Luteinizing hormone releasing hormone analogue (DTRP6 administered in a long protocol, for at least 15 days) was associated with human menopausal gonadotrophin (HMG) induction in group I. In group II, stimulation was performed using HMG alone (three ampoules per day in general, from days 2 to 7 of the cycle). Apart from the well known results demonstrated in the literature of a reduced incidence of inadequate responses, an absence of premature luteinization and a greater number of oocytes per retrieval (8.8 +/- 4.9 versus 6.8 +/- 3.2, P less than 0.01 in group II), this study confirms the higher pregnancy rate (21.1 versus 12.2% per cycle and 24.7 versus 17.1% per oocyte retrieval, not significant) and underlines the higher plasma progesterone levels and lower E2/P ratio in group I from D - 1 to D + 5, which could explain a better maturation of the oocytes and the endometrium.
Plasmatic estradiol (E2), progesterone (P) and LH were measured during the follicular phase of 343 cycles induced for in vitro fertilization (IVF) using a LHRH agonist in a "long protocol" (Group I) and 76 cycles in a "short protocol" (Group II). Moreover measurements in the plasma and follicular fluid (FF) of E2, P, LH, Delta-4-androstenedione (A), Testosterone (T) and prolactin (PRL) were performed on the day of oocyte retrieval (DO) in 46 women of the group I (111 FF) and 27 of the group II (67 FF). In the group I, plasma LH always remains below 3 mUl/ml, whatever the type of agonist (Buserelin or DTRP6-LHRH) and the type of stimulation (HMG or FSH) are used. On the other hand in the group II, mean plasma LH and P levels from D-5 to D-2 and those of FF LH, T and A on DO are significantly higher than in the group I. These changes are associated with a significant decrease of retrieved oocytes (5.8 versus 7.8 p less than 0.0001), pregnancy rate (15% versus 30%, p less than 0.01) and ongoing pregnancy rate (10% versus 22%, per oocyte retrieval, p less than 0.01). They suggest that the pituitary desensitization could be unsatisfactory with the short protocol use of agonist.
The obstetrical outcome of 305 pregnancies obtained by in vitro fertilization were reviewed: out of 275 pregnancies following fresh embryo transfers, 205 (74.5%) were single, 64 (23.3%) double and 6 (2.2%) triple). We observed increased frequencies of high blood pressure linked to older maternal age, bleeding in the late pregnancy and breech presentation, which could be associated to abnormal insertion of umbilical cord and/or placenta. Multiple pregnancies, especially the triple ones, are of the highest risk (intra-uterine growth retardation, low birth weight). Nevertheless the total fetal mortality remains low in our experience. Data about 22 pregnancies following cryopreserved embryo transfer, 5 after oocyte donation and 3 therapeutic abortions are also given.