Saturday, August 28, 2010
Thursday, August 19, 2010
Mullerian malformation Correction
The First Correction Report.( 01 -02 - 2010 ).
Introduction.
The correction of a rare form of Mullerian Dysgenesis was started at A.G.Chromepet Public Health & Maternity Centre, Chromepet, Chennai.600044, as a prospective one, on 01-04-2005. The first case came on 13 - 08 – 2006, after reading a write-up, in “ Muttram “( April, 2006), the official organ of the Tamil Nadu Corporation for Development of Women. Subsequent to a news item, which appeared in a Malayalam daily – “ Mathrubhoomi “ dated 19 - 07 – 2009 ( Sunday ), there has been a spurt of cases from among Keralites ( mainly from Kerala, a few from Mumbai and Bangalore.
The salient features of the correction are as follows: At first appointment, all cases of primary amenorrhoea underwent pre-correction evaluation – (a) clinical examination, followed by (b) biochemical tests and (c) an abdominal scan to identify and confirm the diagnosis of Mullerian Dysgenesis. One notable feature of the scans needs emphasis, (since scans are the sheet anchor of correction), a single observer is bound to give the best results for correction. All who had 46, XX, as karyotype, were then subjected to video-laparoscopy for confirmation and record and then given medicine for one month. They were informed that the karyotype result would be the deciding factor for eligibility for correction. Subsequently every month they were scanned and given medicine. When a scan showed increase of dimension by 0.5 c.m., in any dimension, it was regarded as progress and the next phase of the regime brought forward. The Ayurvedic Regime consists of 11 compounds given in 8 phases. At the end of each quarter the physical response, hormonal status and imaging changes were reassessed and a report made.
(A) Clinical examination: - When one is treating a disease, one checks the relevant body system physically and investigation is directed to it. When one is attempting to correct a birth defect, the response to drugs will depend on the individual’s physical fitness and therefore, the main tests pertaining to all systems have to be done. Moreover, an individual with a defect in the reproductive system may exhibit defects in other systems as well.
(B) Biochemical Tests of blood and urine are done. In the blood, chromosome analysis, hormone assays and general tests of various systems are done. Karyotyping, as mentioned earlier, is the decisive test, as only 46, XX,cases are eligible for the corrective procedure. Hormone assays to find out the levels of the following hormones are done; - Estrogen, Progesterone, Follicle Stimulating hormone, Luteinising hormone, Testosterone and Prolactin. Thyroid hormones are also assessed. General blood tests such as Grouping and Typing, bleeding time, clotting time, haemoglobin estimation, packed cell volume, total and differential counts, erythrocyte sedimentation rate, HbsAg, H.I.V. Tests – I, II, Blood sugar estimation (both fasting and post-prandial), urea, creatinine and uric acid are done. In urine, routine tests for pH, albumin, sugar and deposits.
(C) USG. Scanning done in all cases, after clinical examination. The impression of the sonologist was recorded under the following heads:
(a) Mullerian Dysgenesis: Normal uterus visualized ( with cervical aplasia/hypoplasia and/or vaginal aplasia/hypoplasia ), hypoplastic ( wherein the cervico-corporeal ratio is 1 : 2 ), infantile uterus ( wherein the cervico-corporeal ratio is 2 : 1 ), nodular uterus, rudimentary uterus, vestigial uterus, streak uterus(like a line), or uterine tissue with length, breadth and thickness, no uterus seen but cervix and/or vagina seen
(b) Mullerian Agenesis: when uterus, cervix and vagina are absent.
(c) Gonadal Agenesis: when ovaries are absent.
(d) Gonadal and Mullerian Agenesis: when uterus, cervix, vagina and ovaries are absent.
(e) Mullerian Dysgenesis and Gonadal Dysgenesis.
(f) Mullerian Agenesis and Gonadal Dysgenesis.
(D) Magnetic Resonance Imaging is done, if there is any doubt.
(E) Diagnostic Video-Laparoscopy –to confirm diagnosis, record and commence correction.
From 26 – 07 – 2009 till 31 – 10 – 2009, 26 cases of Primary Amenorrhoea reported for study. As mentioned above, clinical examination followed by karyotyping was done in all cases. This revealed 20 cases with 46, XX, of whom 5 had additional features ( translocation, deletion, mosaicism and insertion ). 5 of them were married and 2 had vaginoplasty before marriage. Of the remaining 6 cases 5 were Turner’s Syndrome and 1 of 46, XY. The 5 who had additional features were as follows:-
(a)mos 46, XX,t(1;3)(1p34.1;3p21) – translocation of chromosome 1p34.1;3p21 in 60% of cells. (1p34.1;3p21) karyotype has been reported with reproductive failure in both men and women. This case has not reported for further evaluation.
(b) 46, XX, ins(2q)(11.1;21.2) mosaic in 20 % of cells. This case has reported and correction started.
(c)46, XX,ins(7p)(p21;p14) mosaic in 20 % of cells She has not reported till date.
(d) Mos 46, XX,del(xy)(q25;q28) in 14 % of cells. She is yet to report.
(e)46, XX,add(22)(p13) in all the cells. She is undergoing correction.
Pre-Correction Evaluation :-
Pre-correction Evaluation is a three fold study based on (1) clinical examination (2) Biochemical tests and (3) USG Scanning to identify and set right deficiencies, if any, so that they become fit and their chances of responding to the correction process become optimal. Of the 20 cases 12 had undergone diagnostic video-laparoscopy and are now undergoing correction. The evaluation of these 12 cases, prior to correction is given below:-
A. Clinical ( including family history and relevant earlier reports )
(1) Age. In the group 14-16 there were 4 cases and 3 cases in 17-19
group but the majority (5) were in the 20-39 group.
(2) Height. Only 1 case was below 155 cms.
(3) Body Mass Index. 8 were normal and the rest underweight.
(4) There was no obvious case of goiter or hirsutism.
(5) There was no case of discharge from nipples and Tanner
staging of the breasts showed 1 of stage 3, 2 of stage 4 and the
rest stage 5.
(6) As regards hair, in the axillae – there were no case of stage 1, 1
case of stage 2 and the rest showed stage 3 and in the pubic
region all the cases were in stage 5.
(7) External Genitalia examination did not reveal any case of fused labia and vagina was present in 6 cases and in 4 cases there was introital depression and in2 cases vagina was totally absent.
(8) Vaginal examination in the 2 married women revealed uterii smaller than normal but in 1 it was in the midline and in the other it was laevo-posed.
(9) Rectal examination showed presence of uterus or uterine nodules in 6 cases and in the rest nothing was palpable. Right ovary was palpable in 2 cases, of which 1 was tender.
(10) Family History. Two of the cases were married and the rest single. Neither of them had attained menarche but one had withdrawal bleeding from the age of 15 for 8 years. She stopped medication 8 years ago and since then, has not had any bleeding P.V. The other did not respond to any medication. There was no case of delayed menarche in any family member and no other member in the family had a similar complaint.
(11) Associated Anomaly. 1 case had associated congenital anomaly
of the Cervical vertebrae and had partial loss of hearing.
B. Biochemical Tests.
(1) Karyotyping: ( only 46,XX, were taken up for correction )
As mentioned earlier, 2 who showed additional features, are undergoing correction. The laboratory has suggested molecular test for SRY Gene in 2 cases and FISH in one case.
(2) Hormone Assays. Estrogen, Progesterone, FSH and LH were within normal limits in all cases. Testosterone estimation revealed 1 of low level and 1 of high level. Prolactin levels were within normal limits in 11 cases and the last one showed below normal limits. As regards Thyroid profile, T3 and T4 were within normal limits in all cases but TSH Levels were high in 1 case and low in the other case.
(3) Blood Group and Type.- Of these 12 cases, 3 were A group, 4 were B group and the remaining 5 were O group. There was 1 case of Rh negative and the remaining 11 were Rh positive.
(4) General –
Hb. – the least was 10.5 and the highest 12.5 and P.C.V. ranged between 32 and 38. Other blood parameters were within normal limits.
Urine – Except for aciduria in all cases, there were no specific changes.
(5) Palm Print – The presence of ‘ Open Fields ‘ over the thenar eminences was studied. There were 7 cases of bilateral O.F., 2 on right, 1 on left and in 2 cases there were no O.F.
(6) Natal Chart – The study is not complete and hence will be given in the next correction report.
C. USG Scanning. Impressions.
Mullerian Dysgenesis | 7 |
Mullerian Dysgenesis and Gonadal Dysgenesis | 1 |
Mullerian Agenesis | 1 |
Mullerian Agenesis and Gonadal Dysgenesis | 2 |
Mullerian Agenesis and Gonadal Agenesis | 1 |
In one case there was a pelvic kidney on the left side.
D. M.R.I. ( abd. ) was resorted to in 1 case viz., the case in which both M.Agenesis as well as Gonadal Agenesis were reported, as it was felt that no purpose would be served by developing the M.System in the absence of the gonads and to exclude ectopic site of gonads. The impression of the MRI was as follows;- uterus and cervix not visualized, visualization of vagina between bladder and rectum – 6 cms., bilateral ovaries seen, normal in size and contour just deep to the anterior abdominal wall above the inguinal ligament, right ovary being anterio-medial and left ovary anterior to external iliac vessels.
E. Diagnostic Video-laparoscopy. There were 2 uterii, one in the midline and 1 to the left of midline. In 8 cases, there were bilateral nodules. There were 2 cases of unilateral nodules, 1 on the left and 1 on the right.
F. Serial USG Scans. The first phase of correction is for 4 months and is intended to increase size. Only 4 cases have completed the first phase of correction.
Case # | Clinical | Biochemical | Imaging |
Case 1 | BMI No change | Hormones - Estrogen 29.4 to 262.37 | Uterine Nodule Thickness from 1.7 to 2.4 |
Case 2 | No change | Hormones - Testosterone 0.514 to 64.23 | Breadth from 0.9 to 1.1 |
Case 3 | No change | Normal | Length from 4.5 to 6.0 ( Since there was an increase of more than 0.5 cm. the next phase was started after the third month.) |
Case 4 | No change | Normal | Breadth from 0.6 to 1.1 Thickness from 0.8 to 1.7 |
It is too premature to assess progress but indications are present.
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