The method of treatment of infertility caused by endometriosis
The invention relates to medicine, namely, gynecology, and can be used to restore the fertility of women suffering from endometriosis. The method includes assigning Duphaston from the 15th to the 25th day of the menstrual cycle, and from the 5th day of the menstrual cycle include intramuscular reaferona according to the scheme: 5, 6, 8, 10, 12, 14 days of the menstrual cycle on 1,000,000 Units, and the course of treatment is three to six months. The method allows to increase the efficiency of treatment by assigning reaferona in the days increase the sensitivity of receptors in the target organ, to reduce the rate of reception of hormonal preparations. table 1.
The invention relates to medicine, namely gynecology.
In the last decade marked increase in the frequency of endometriosis from 12 to 27% operated gynecological patients, 20-47,8% of women of them suffer from infertility .
A modern approach to the treatment of endometriosis is the combination of surgical technique aimed at maximum removal of endometriotic lesions, hormonomodulizing therapy with the use of the funds has a direct or indirect effect on the metabolism of steroids. However, noted the traditional complex of therapeutic measures [3, 4, 5]. Insufficient efficiency of recovery of fertility in patients with endometriosis requires the development of new approaches to therapy.
Closest to the proposed method is the treatment of patients with genital endometriosis using a new inducer of interferon - "Cold" (Genital endometriosis: new approaches to therapy. A guide for physicians under the editorship of doctor of medical Sciences S. A. can be written. ISBN 5-85-792011-06©. The team of authors. 1997. St.-Petersburg).
However, this method cannot be used to restore the fertility of women suffering from endometriosis. Cycloferon is applied from the 1st day of the menstrual cycle, when the sensitivity of target organs is minimal, which reduces further the effectiveness of hormonal preparations. Its effect is based only on the immunomodulating action; the drug does not possess antiproliferative activity, does not inhibit angiogenesis and is not a regulator of differentiation and phenotypic reversion of proliferative processes.
The problem to be solved by the proposed method is to increase the effectiveness of treatment of infertility caused by endometriosis.
The task to solve due to the fact that the 5th is the local injection of 1,000,000 Units, the course of treatment for three to six months.
The proposed method is carried out by conducting the treatment of endometriosis using Reaferona-EU (human recombinant interferon - alpha 2b protein synthesized by the bacterial strain Escherichia coli) the scheme developed: IFN 1 million IU intramuscularly on 5, 6, 8, 10, 12, 14, day of the menstrual cycle, then Duphaston 10 mg per os in a cyclic mode with 15 to 25 day of the menstrual cycle. With the goal of hormonal therapy is used Duphaston, as this drug does not affect ovulation; and the occurrence of pregnancy is possible on the background of therapy. The proposed scheme is used for three to six menstrual cycles with frequency estimation of pregnancy.
We observed 91 woman suffering endometrioza.sleduet infertility. Age of respondents ranged from 19 to 35 years, averaging 26,7±2, duration of infertility was an average of 4.6±2.4 years. Individuals were divided into two clinical groups: in the first (control) group included 60 women who used traditional treatment; the second (main) included 31 patients in the combined therapy endometriosisortho all patients received Duphaston in cyclic mode. The results of the treatment were determined three months after treatment.
Based on the results of studies on these Adamyan L. C., Kulakova C. I.  it is shown that control the dynamics of the level of encountering (CA 125, CA 19-9, CEA) in serum may serve as one of the diagnostic criteria and evaluate the effectiveness of the combined treatment, as well as factor in early detection of recurrence of endometriosis. Evaluated the role of autoimmune markers in the pathogenesis of infertility in endometriosis and the necessity of examination of patients with endometrioza.sleduet infertility to determine the concentration encountering in the serum. Determination of increased levels of CA-125, CEA, CA 19-9 has a high information content in relation to the recurrence of endometriosis.
The effectiveness of the treatment is assessed according to the following criteria: determined the level of encountering CA-125, CEA, and CA 19-9 in serum, the analysis which was carried out by enzyme-linked immunosorbent assay (ELISA). The studied parameters were evaluated before and after therapy, all the obtained data were processed by the method of variation statistics. The reliability was determined by table t-test, the results are presented in the table
Pitney group, which in turn eliminates additional courses of therapy, thereby reducing the cost of treatment.
One of the main criteria was the pregnancy rate, which was in the control group 24 (40%), in the main 15 (48.4%) of pregnancies.
Thus, the results indicate the efficiency of the treatment of infertility caused by endometriosis, with the introduction in the traditional regimen of referee, as evidenced by the increase in the pregnancy rate.
Example 1. Patient Century to 31 years, with 12.06.96 was at the dispensary for infertility in consultative-diagnostic center of the City hospital № 4 for 6 years. During the observation was carried out a full range of laboratory and diagnostic activities. From the anamnesis: somatically healthy menstruation from the age of 11, was established immediately after 5-6 days 28-30 days, the regular, the first two days of abundant, then moderate, in the last few years, notes the pain. The study plots basal temperature within three months confirmed the presence of ovulation. When vaginal bimanual study found granulomas formation in the projection PR is e appendages - echo revealed no pathology, in the projection of the right ovary tumor formation up to 4.0 cm in diameter. Conclusion: ovarian cyst. The blood analysis on hormones on day 10 of the menstrual cycle was as follows: LH-17,2 IU/l, FSH is 1.6 mIU/l, PG-1.9 nmol/l, eh - 613 nmol/L.
Further investigated the level of encountering: CA-125 OF 26.4 IU/l, CA-19-9 25,7 IU/l, CEA 3,11 ng/ml (thereby confirmed the presence of endometriosis).
21.06.00 in the Department of infertility City hospital № 4 about like formation of the right ovary in the planned order has been executed, the operating laparoscopy, during which it was found: the uterus, left the uterus, the right fallopian tube is macroscopically not changed, the right ovary is enlarged due to cysts on the peritoneum small foci of endometriosis. Produced enucleation of the cyst, selecting the capsule was opened, the content is "chocolate", cauterization foci of endometriosis. When conducting chromosulphuric confirmed the patency of the fallopian tubes. Conclusion: external genital endometriosis, endometriotic cyst of the right ovary. The patient was discharged on the 6th day after surgery in satisfactory condition. Assigned to hormonal therapy Duphaston from 15 to 25 deal again with the same complaints on infertility, dysmenorrhoea, pain in the lower abdomen. When you re-inspection, the level of encountering were as follows: CA-125 25,17 IU/l, and CA 19-9 23,8 IU/l, CEA of 2.4 ng/ml bimanual study found tumorous formation of the left ovary, ULTRASOUND examination confirmed the presence of a cyst of the left ovary. 12.02.01. After re-laparoscopy detected endometrioma left ovary produced enucleation of the cyst. At discharge the patient the recommended course of therapy.
Example 2. Patient S. 28 years, 07.09.01 addressed in the consultative diagnostic center of the City hospital № 4, with complaints of infertility for 5 years. Husband examined healthy. The woman is at the dispensary. At follow-up was conducted a set of laboratory diagnostic procedures. Clarified the following: somatically healthy menstruation for 12 years, was established immediately after 6 days, after 28 days, regular, moderate, over the last 6 years notes soreness. The study plots basal temperature within three months confirmed the presence of ovulation. When vaginal bimanual study found granulomas formation in the projection of the right ovary sensitive during the inspection; uterus, left pridatkina, in the projection of the right ovary tumor formation up to 5.0 cm in diameter. Conclusion: ovarian cyst. The blood analysis on hormones on day 7 of the menstrual cycle was as follows: LH - 19 DMA/l, FSH and 1.7 mIU/l, PG - 2.4 nmol/l, eh - 554 nmol/L.
Further investigated the level of encountering: CA - 125 27,1 IU/l, CA - 19-9 22,6 IU/l, CEA of 2.16 ng/ml
Given the complaints about infertility and the presence of granulomas formation of the right ovary, 20.04.02 in the planned order has been executed, the operating laparoscopy, during which it was found: the uterus, left the uterus, the right fallopian tube is macroscopically not changed, the right ovary is enlarged due to a cyst in the upper pole, the peritoneum red space separate foci of endometriosis. Produced enucleation of the cyst, selecting the capsule was opened, the content is "chocolate", cauterize lesions of endometriosis, sanation of abdominal cavity. When conducting chromosulphuric confirmed the patency of the fallopian tubes. Conclusion: external genital endometriosis, endometriotic cyst of the right ovary. The patient was discharged on the 5th postoperative day in good condition. Assigned to the following treatment: IFN scheme: 5, 6, 8, 10, 12, 14 day IU the yawl three months.
One month after a course of therapy with repeated inspection level encountering were as follows: CA-125 24,56 IU/l, CA19-9 OF 20 IU/l, CEA - 2,13 ng/ml In October the examined pregnancy.
Thus, the proposed method for the treatment of infertility caused by endometriosis, using reaferona allows you to increase the effectiveness of therapy, to reduce the rate of reception of hormonal preparations and to reduce the number of relapses due to the fact that the preparation is applied from the 5th day of the menstrual cycle, when significantly increases the sensitivity of target organs. The drugs are based on the regulation of expression of receptors of sex steroid hormones and inhibition of angiogenesis that is pathogenetically substantiated treatment endometriosisortho infertility.
Sources of information
1. Adamyan L. C., fists Century. And. Common forms of genital endometriosis. M., 1996, S. 10-12.
2. Kuzmichev L. N., Leonov B. C., Smolnikova C. Y., Cindrova L. B., Belyaev A. A. Endometriosis: Etiology and pathogenesis, the problem of infertility and modern solutions in the program of in vitro fertilization. Obstetrics and gynecology. 2001, No. 2, S. 8-10.
3. Strizhova N. In., Sergeantat with endometrial hyperplastic processes in combination with uterine myoma. Obstetrics and gynecology. 1998, No. 3, S. 32.
4. Ranaey J., Archer D. Peritoneal fluid: its relevance to the development ofendometriosis. Fertil Steril 1993; 60. - P. 1-14.
5. Rock J., Mentos D. M. // Br. J/ Obstetr. Gynaecol. - 1992. - Vol. 99. - Supp l7.-P. 1-4.
Treatment of infertility due to endometriosis by adjuvant therapy, including the appointment of Duphaston from the 15th to the 25th day of the menstrual cycle, characterized in that the 5th day of the menstrual cycle include intramuscular reaferona according to the scheme: 5, 6, 8, 10, 12, 14 days of the menstrual cycle on 1,000,000 Units, and the course of treatment is three to six months.
R2IS-H, -OH, -O(C1-C4alkyl), EA6H5, CCA(C1-C6alkyl) , -OSO2(C2-C6alkyl), or halogen; R3- 1-piperidinyl, 1-pyrrolidinyl, methyl-1-pyrrolidinyl, dimethyl-1-pyrrolidinyl, 4-morpholino, dimethylamino, diethylamino, diisopropylamino or 1 hexamethyleneimino; n = 2 or 3; Z Is-O - or-S-, or their pharmaceutically acceptable salts