Christophe Lelaidier

Methotrexate treatment of ectopic pregnancy : 100 cases treated by primary transvaginal injection under sonographic control

Objective To evaluate safety and efficacy of intrasaccular methotrexate (MTX) for treatment of ectopic pregnancy (EP). Design Longitudinal nonrandomized trial of MTX treatment of EP. Setting Department of Obstetrics and Gynecology (A. Beclere Public Hospital, Clamart, France Paris-Sud University). Patients One hundred patients with an EP visualized by sonography. Patients were 31.4 ± 4.8 years old, para 0 to 4, and gravida 0 to 7. Twelve patients had a past history of EP, and 18 had previously undergone tubal surgery. Inclusion score for proposed medical treatment used six criteria graded from 1 to 3: gestational age, initial hCG level, P level, existence of abdominal pain, size of hemoperitoneum, and diameter of hematosalpinx. Eleven patients had an EP with cardiac activity. Treatment consisted of MTX, 1 mg/kg, given locally under transvaginal sonographic control. Results Eighty-three of 100 patients were considered to be completely cured (return of hCG to 12. Twenty-eight of 83 patients treated successfully required more than one injection of MTX (additional doses being given intramuscularly) because of nonresolution of hCG levels. Follow-up hysterosalpingography was performed in 80 patients showing 90% tubal patency on the side of the treated EP. Of 58 patients wishing pregnancy, 34 pregnancies occurred, including 25 ongoing or delivered. We observed a low recurrence rate of EP (3 with 1 on the same side). Conclusion Treatment by initial transvaginal injection of MTX under sonographic control appears to be simple and effective, with no demonstrable untoward effects. The tubal patency and subsequent fertility obtained appear satisfactory. The highest success rate is observed when hCG level is under 5,000 mIU/mL and/or a pretherapeutic score ≤ 12 when EP is visualized by sonography.

Nonsurgical treatment of heterotopic pregnancy: a report of six cases

OBJECTIVE To evaluate nonsurgical management of heterotopic pregnancy. DESIGN Retrospective case series. SETTING Department of Obstetrics and Gynecology (Antoine Béclère Hospital, Clamart, France, Paris-Sud University). PATIENTS Six women with heterotopic pregnancy who conceived in four cases after ovulation induction. INTERVENTION Transvaginal ultrasound (US)-guided aspiration/injection of potassium chloride (KCl) was performed in three cornual pregnancies with alive embryo. Expectant management was realized in three other cases. The regression was followed by serial US examination. MAIN OUTCOME MEASURES Early and late complications related to the procedure, outcome of intrauterine pregnancy (IUP). RESULTS Five of six patients were treated successfully (3 with KCl and 2 after expectant management). Three of these five patients had a spontaneous vaginal delivery, and two abortions occurred in the remaining two patients. Salpingectomy had to be performed in one case 10 days after medical treatment. This twin pregnancy ended with an abortion at 23 weeks of amenorrhea. Four cornual heterotopic pregnancies were treated successfully. No complication occurred after the initial management. CONCLUSION Ultrasound permits a reliable and early diagnosis of heterotopic pregnancy. In such cases nonsurgical management is an efficient alternative with a good IUP prognosis.

Treatment of unruptured tubal pregnancy with methotrexate: pharmacokinetic analysis of local versus intramuscular administration*

OBJECTIVE To determine the optimal dose and route of methotrexate (MTX) in the treatment of ectopic pregnancy (EP). DESIGN Prospective randomized study. SETTING Department of Obstetrics and Gynecology (A. Béclère Public Hospital, Clamart, France, Paris-Sud University). PATIENTS AND METHODS Forty-eight patients with unruptured EP clearly visualized by ultrasound were randomly allocated into four groups of treatment (12 patients in each group): group 1, 1 mg/kg injected locally in the ectopic gestational sac and 1 mg/kg by IM administration 48 hours later; group 2, 1 mg/kg locally; group 3, 0.5 mg/kg locally; group 4, 1 mg/kg by IM administration. Inclusion criteria used a pretherapeutic score < or = 12. Blood samples were collected at time 0.25, 0.5, 1, 2, 6, 12, 24, 36, and 48 hours after MTX administration. Pharmacokinetics of MTX plasma levels were measured by fluorescence polarization immunoassay. Kinetic parameters were compared by Wilcoxon test and Mann-Whitney test. Plasma hCG concentrations were assessed on days 2, 5, and 10 and then weekly until they returned to undetectable levels. RESULTS Success rate was 12 of 12, 11 of 12, 10 of 12, and 10 of 12 in groups 1, 2, 3, and 4, respectively. Six patients in group 3 required an additional MTX IM injection because of an inadequate decrease of hCG plasma levels. Five patients underwent surgery for abdominal pain or inadequate decrease of hCG. Area under the curve decreased more rapidly after injection in the gestational sac alone than after IM injection and was similar in groups 1 and 2 after local injection and lower in group 3. Terminal half-life and mean residence time remained similar in the four groups. Systemic side effects of MTX therapy occurred in three cases in groups 1 and 4. The regression curve of hCG plasma levels appeared similar in the four groups with a decrease to pretreatment values between days 6 and 8 after an initial rise after MTX was given. CONCLUSION Area under the curve found after injection in the ectopic sac may be related to a decrease in bioavailability of MTX that links to trophoblastic cells. Patients in group 3 were clearly undertreated by 0.5 mg/kg MTX and required additional therapy. Residual values of MTX plasma levels were always below the limit of detection of our assay and confirmed that citrovarum factor rescue is unnecessary. Injection of 1 mg/kg of MTX in the ectopic sac appears as effective as systemic (IM) injection with less side effects for the patients.

Ultrasound-guided injection of methotrexate versus laparoscopic salpingotomy in ectopic pregnancy

OBJECTIVE To compare local injection of methotrexate (MTX) under sonographic control to laparoscopic salpingotomy for conservative management of ectopic pregnancy (EP). DESIGN Prospective randomized study. PATIENTS Forty patients were randomized into two groups using a random number table. Inclusion criteria were an EP visualized by ultrasound with a pretherapeutic score < or = 13 as assessed by six criteria graded from 1 to 3: gestational age, hCG level, P level, abdominal pain, volume of the hemoperitoneum, and diameter of the hematosalpinx. INTERVENTIONS Group 1 patients injected transvaginally with 1 mg/kg MTX into the EP without anesthesia versus group 2 patients undergoing laparoscopic salpingotomy. MAIN OUTCOME MEASURES Postoperative hospital stay, decrease of hCG levels, success rate. RESULTS The success rates, defined by hCG levels returned to normal (< 10 mIU/mL [conversion factor to SI units, 1.00]), were 19 of 20 in both groups. Medical treatment was associated significantly with shorter postoperative stay (24 versus 46 hours) and a higher initial hCG level. Human chorionic gonadotropin returned to normal more quickly after laparoscopic treatment (14 versus 28 days). CONCLUSIONS In selected cases of EP with a pretherapeutic score < or = 13, MTX treatment appeared to be as safe and efficient as was conservative treatment by laparoscopy.

Comparison of short 7-day and prolonged treatment with gonadotropin-releasing hormone agonist desensitization for controlled ovarian hyperstimulation

OBJECTIVE To compare two treatment regimens associating a gonadotropin-releasing hormone agonist (GnRH-a) and human menopausal gonadotropin (hMG) for controlled ovarian hyperstimulation (COH). DESIGN A prospective randomized trial. SETTING The outpatient fertility clinic of a university tertiary care center, the Hôpital A. Béclère, Clamart, France. PARTICIPANTS One hundred eighty-two in vitro fertilization (IVF) candidates undergoing new or repeat IVF cycles at Hôpital A. Béclère over a 4-month period. TREATMENT Group 1 (7-day protocol): A short-acting preparation of GnRH-a (Tripteriline 0.1) was administered daily for 7 days, starting on cycle day 2. Ovarian stimulation with hMG was started on cycle day 4. Group 2 (long protocol): A timed release preparation of GnRH-a (Tripteriline 3.75 mg) was administered on cycle day 2. Ovarian stimulation with hMG was started after documented ovarian suppression. MAIN OUTCOME MEASURES Response to COH, pregnancy rate (PR), tolerance. RESULTS In the 7-day protocol, the amount of hMG required was markedly lower at 24 +/- 7 than in the long protocol group requiring 42.5 +/- 9.75 vials (75 IU) (mean +/- SD). No elevation of plasma LH occurred in either group. The number of oocytes retrieved was 7.3 +/- 1 and 10.7 +/- 1.2 (mean +/- SD) in the 7-day and long protocols, respectively. Yet, the number of embryos obtained and the PRs were similar in the two treatment groups. CONCLUSIONS We observed that in COH, GnRH-a treatment could be interrupted safely several days before human chorionic gonadotropin administration without risking a premature increase of plasma luteinizing hormone. Moreover, the number of embryos available for fresh transfer and the ongoing PRs were similar in the new 7-day and in the classic long GnRH-a/hMG protocols, despite the smaller number of oocytes suggesting a greater efficiency of the 7-day protocol. The peak estradiol level and the hMG requirement were also lower in the 7-day GnRH-a/hMG protocol.

Endometrium preparation with exogenous estradiol and progesterone for the transfer of cryopreserved blastocysts

OBJECTIVE To determine the implantation rates of cryopreserved blastocysts using controlled E2 and P replacement cycles in women with functioning ovaries. DESIGN Retrospective clinical study. SETTING University teaching hospital. PATIENTS Infertile women with cryopreserved blastocysts obtained from previous IVF attempts. INTERVENTIONS Exogenous E2 was administered orally from cycle day 1 and P was started transvaginally from day 15. Blastocysts were transferred on the 5th day of endometrial exposure to P (day 19). MAIN OUTCOME MEASURES Blastocyst implantation rate and pregnancy rate (PR). RESULTS Ninety-eight percent of blastocysts survived thawing: 67 were transferred in 42 women. Eight pregnancies occurred giving a PR of 19% per ET and 11.9% per blastocyst. CONCLUSION The high PR observed after transferring blastocysts on the 5th day of endometrial exposure to P in controlled E2 and P replacement cycles speaks for a forward slide of the window of transfer in case of blastocysts.

Conservative management of ectopic pregnancy: prospective randomized clinical trial of methotrexate versus prostaglandin sulprostone by combined transvaginal and systemic administration

In a prospective randomized study, 21 patients with an unruptured tubal pregnancy were treated with local and systemic injection. On the day of diagnosis, methotrexate (MTX) (1 mg/kg) or sulprostone (500 micrograms) were injected into the gestational sac under transvaginal sonographic control. The systemic component consisted of an intramuscular injection of MTX (1 mg/kg) 3, 5, and 7 days after local injection or of sulprostone (500 micrograms) on the 1st 2 postlocal injection days. Methotrexate therapy was successful in 8 of 12 patients and sulprostone therapy in 6 of 9. Laparoscopy was then performed on the 7 unsuccessful patients: 3 of them had pain and hemoperitoneum and 4 of them had rising human choriogonadotropin (hCG) levels. One stomatitis after MTX and one cramping abdominal pain were observed. Thirteen of 14 successfully treated patients had initial hCG levels less than 5,000 mIU/mL. At subsequent hysterosalpinography, 13 of 14 patients had normal tubal configuration and patency. Three of 10 patients who desired another pregnancy had already achieved a normal intrauterine pregnancy. These results suggest that MTX and sulprostone were equally effective, and medical approach for the unruptured ectopic pregnancy may be restricted to patients with hCG less than 5,000 mIU/mL.

Methotrexate Treatment of Ectopic Pregnancy: 100 Cases Treated by Primary Transvaginal Injection Under Sonographic Control

OBJECTIVE To evaluate safety and efficacy of intrasaccular methotrexate (MTX) for treatment of ectopic pregnancy (EP). DESIGN Longitudinal nonrandomized trial of MTX treatment of EP. SETTING Department of Obstetrics and Gynecology (A. Béclère Public Hospital, Clamart, France Paris-Sud University). PATIENTS One hundred patients with an EP visualized by sonography. Patients were 31.4 +/- 4.8 years old, para 0 to 4, and gravida 0 to 7. Twelve patients had a past history of EP, and 18 had previously undergone tubal surgery. Inclusion score for proposed medical treatment used six criteria graded from 1 to 3: gestational age, initial hCG level, P level, existence of abdominal pain, size of hemoperitoneum, and diameter of hematosalpinx. Eleven patients had an EP with cardiac activity. Treatment consisted of MTX, 1 mg/kg, given locally under transvaginal sonographic control. RESULTS Eighty-three of 100 patients were considered to be completely cured (return of hCG to < 10 mIU/mL). The success rate was 92.8% with an initial hCG level < 5,000 mIU/mL and 87% when the score was < or = 12. Seven of the 11 patients with an EP with cardiac activity were treated successfully, including 5 of 7 when the initial score was < or = 12, and all failures concerned cases with an initial score > 12. Twenty-eight of 83 patients treated successfully required more than one injection of MTX (additional doses being given intramuscularly) because of nonresolution of hCG levels. Follow-up hysterosalpingography was performed in 80 patients showing 90% tubal patency on the side of the treated EP. Of 58 patients wishing pregnancy, 34 pregnancies occurred, including 25 ongoing or delivered. We observed a low recurrence rate of EP (3 with 1 on the same side). CONCLUSION Treatment by initial transvaginal injection of MTX under sonographic control appears to be simple and effective, with no demonstrable untoward effects. The tubal patency and subsequent fertility obtained appear satisfactory. The highest success rate is observed when hCG level is under 5,000 mIU/mL and/or a pretherapeutic score < or = 12 when EP is visualized by sonography.