HISTOPATHOLOGICAL EXAMINATION OF TISSUES FOLLOWING A SURGICAL UTERINE EVACUATION IN THE FIRST TRIMESTER BLEEDING: CLINICAL RELEVANCE

Background: There is no general consensus about the role of routine HPE of the obtained tissue at the time of uterine evacuation. However, it is understood clinically that it is of utmost importance to prove the presence of intrauterine gestation and to exclude gestational trophoblastic disease in the form of partial or complete mole. This study aimed to assess the role of histopathology in cases of first trimester miscarriages and to determine clinical relevance of histopathological examination following surgical evacuation.


INTRODUCTION
Normal uneventful pregnancy resulting in a healthy baby and healthy mother is a blessing of the nature, unfortunately, some pregnancies are affected by various complications. The most common problems associated with bleeding in first trimester pregnancy are miscarriages, ectopic and molar pregnancies. These conditions are not clinically differentiated if conceptus tissue is not sent for histopathological examination (HPE). if the molar pregnancies are missed, this would lead to prolonged follow up and serious implications on maternal health. There is no general consensus about the role of routine HPE of the obtained tissue at the time of uterine evacuation, however, it is clinically understood that it is of utmost importance to prove the presence of intrauterine gestation and to exclude gestational trophoblastic disease in the form of partial or complete mole. 1 There is a medicolegal aspect related to clinical practice suggesting that in all uterine evacuations a sample of tissues should be submitted for histopathological examination to confirm the presence of intrauterine fetal tissue. 2 It is often hoped especially in the clinical setting of recurrent spontaneous miscarriages, the further diagnostic information explain-ing the underlying cause of pregnancy loss may be obtained from examination. 3 An alternative approach is to examine the products only when there is a definite indication, such as when there is uncertainty about the diagnosis either pre-operative or during surgery. 4 There are limited researches regarding this subject matter in this region. This study aimed to assess the role of histopathology in cases of first trimester miscarriages and to determine clinical relevance of histopathological examination following surgical evacuation.

METHODS
This was a retrospective study of patients attended at an agency for reproductive health in the Department of Obstetrics and Gynecology, Chitwan, Nepal from 2018 January to December 2018 with the diagnosis of miscarriage. All consecutive patients with history first trimester abortion (up to 12 weeks) without any preexisting medical co-morbidities were included while normal pregnancies with IUCD in situ was excluded. We considered first trimester abortion as early pregnancy loss which is defined as non-viable intrauterine pregnancy with either an empty gestational sac or gestational sac containing an embryo or fetus without fetal heart activity within the first 13 weeks of gestation (NICE, 2012). 5 The secondary data from patients' record files were collected on different variables like socio-economic status, level of literacy, occupational status of the patients. Demographic data including the age, parity, gestational age, use of medical termination pills (MTP), the surgical evacuation was performed in all patients. In patients included in this study, all the retained products removed surgically are routinely subjected to histopathological examination. The data was analyzed using descriptive statistics like percentage, stander deviation, mean, range in Microsoft Excel software. A p value <0.05 was considered for the statistical significance.

RESULTS
Out of all cases of abortion presenting to the hospital, a total number of 60 cases were diagnosed to have first trimester abortion. The mean age of the women was 27.3 years and ranged from 18 to 40 years. The parity ranged from 0 to 7 showed mean: 2.11± There was no significant difference (p=0.609[95%CI]) in the occurrence of abortions in multigravida 32 (53.33%) and in primigravida 28 (46.66%). Regarding occupations majority (53%) were housewives followed by 23% medical personnel, 10% bankers, 7% teachers, 5% entrepreneurs and 2% students.
Majority of the patients presented with bleeding per vaginum 23(38.33%), 16 patients (26.66%) presented with scanty spotting per vaginum and the rest of them 21(35%) were detected to have missed abortion at routine first antenatal scan. The use of MTP was also studied in multigravida and the primi-gravida. Out of 15 MTP users in this study, multigravidas were observed to have used MTP more frequently 13 (86.66%) than the primigravida 2 (13.33%) (Figure 1). Most common type of abortion encountered in the MTP users was found to be the incomplete abortion 12 (80%) ( Table 2).  All the HPE reports confirmed the presence of pregnancy. Products of conception (POC) was seen in 52 (86.66%) patients, partial molar pregnancy in 6(10%) patient and a diagnosis of complete molar pregnancy found in 2(3.33%) patients ( Figure 2). proximately 10-20% of clinical pregnancies are lost spontaneously during the first trimester which is defined as the first 12 to 14 weeks. [7][8] Miscarriage is a common condition in the first trimester of pregnancy and like many other disorders the accurate diagnosis is necessary for the management. But in some cases, it may be misdiagnosed when another condition that requires immediate treatment or long term follow up as an ectopic pregnancy or gestational trophoblastic disease exists. 9 Ultrasound, quantitative beta human chorionic gonadotropin (B-HCG) testing and histopathologic examination of the uterine products are diagnostic tools to determine the type of miscarriage and to differentiate miscarriages from other conditions. Some studies 1,11,12 have found numerous pathologies in tissue from first trimester miscarriages, including complete mole, partial mole, exaggerated placental site, placental site trophoblastic nodule and decidual tissue. The authors of these studies concluded that routine histopathologic assessment of products of first trimester spontaneous miscarriages can lead to the diagnosis of important pathologies, more effectively identify ectopic pregnancies or infections than clinical or other laboratory criteria and may reduce mortality. By contrast, others have recommended against routine histopathological examination of tissues from first trimester miscarriages.

**POC: Product of conception
Heath et al 9 found only two molar changes (0.13%) and two (0.13%) ectopic pregnancies among 1576 patients on histopathological evaluation of tissues removed during therapeutic or emergency uterine evacuation for spontaneous miscarriages. They recommended that histological examination of the products of conception should not be routinely performed at surgical termination of pregnancy.
In our study, we agree with studies by Novak et al 14 and El-Halaby et al. 12 In study by Novak et al that all the tissues should be submitted to histopathological examination to investigate whether the abortion was due to dysmorphic changes or disruptive causes, to exclude the presence of trophoblastic disease and sometimes simply to confirm that pregnancy had occurred by showing the presence of fetal/placental tissues. EL-Halaby et al 12 reported 3.1% cases of partial mole, 1.25 cases of complete mole, 1.2% cases of ectopic pregnancy while Fram et al. 10 reported 17% partial mole from 293 biopsies. They concluded that routine histopathology of first trimester miscarriages is very valuable as important findings like trophoblastic diseases and ectopic pregnancy can be diagnosed thus saving the lives of these patients. 10,12 In our study 6 patients (10%) had partial molar pregnancy and 2(3.33%) had complete molar pregnancy. The molar group was followed up by weekly serum beta human chorionic gonadotropin level measurement till a negative level was obtained, thereafter monthly for next 6 months. The study by Alsibiani et al 3 shows the incidence of missed abortion was the commonest (45.3%) during admission as compared to 55% in our study. In our study,16 patients (48.5%) of missed miscarriage were detected during routine antenatal scan, 14 (42.42%) presented with scanty spotting per vaginum, 3 (9%) presented with heavy bleeding per vaginum.
A remarkable finding in this study is the increased risk of miscarriage among housewives which was significantly higher than rest of the study group.
Another observation was that the use of medical termination pills was found to be higher in multigravida 13(86.66%) than in primigravida 2(13.33%).The mean gestational age at first routine antenatal checkup in primigravida was 8.1 weeks whereas in multigravida it was 11.6 weeks .This gives the emphasis on making antenatal care more effective on making the women aware of the need for early health seeking behavior, the risks of miscarriages and ectopic pregnancies well explained to them.
Another significant finding was that 25% of patients in our study required blood transfusion due to severe blood loss during the process. Out of these 25% patients, 73% patients had incomplete abortion with heavy blood loss. This issue can be addressed by the proper education regarding the use of medical termination pills and to report immediately once they notice heavy flow. This way we can reduce the maternal morbidity and mortality.
The limitations of our study include a risk of potential observer bias, and this being a very small sample size, large-scale studies need to be done before formulating any plans.

CONCLUSION
In our study, histopathological assessment proved to be a vital tool in detecting molar pregnancy. It is very obvious from our study that histological results showing partial mole in 10% patients and complete mole in 3.33% patients. This 13.33% of molar pregnancies would have been missed without the histopathological analysis. We recommend that all the tissues obtained from the uterine evacuation in the first trimester should be routinely submitted for histopathological examination.