Very early pregnancy loss in adolescent females: Diagnosis, evaluation and conservative management

Very early pregnancy loss in adolescent females: Diagnosis, evaluation and conservative management

Adolesc Pediatr Gynecol (1989) 2: 106-110 Adolescent and Pediatric Gynecology e 1989 Spring er-Verlag New York Inc. Very Early Pregnancy Loss in Ad...

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Adolesc Pediatr Gynecol (1989) 2: 106-110

Adolescent and Pediatric Gynecology

e 1989 Spring er-Verlag New York Inc.

Very Early Pregnancy Loss in Adolescent Females: Diagnosis, Evaluation and Conservative Management Elaine E. Yordan, M.D . 1 and Robert A. Yordan , M.D . 2 'Departme nts of Pediatr ics and 20 bstetrics and Gyneco logy . University of Connecticut Health Cen ter , Farmi ngton, and 'Saint Francis Hospital and Medical Center , Hartford, Co nnecticut

Abstract. A high index of suspicion and the availability of accurate human chorionic gonadotropin (hCG) testing were useful in the diagnosis and co nse rvative management of very earl y pregnan cies and their spo ntaneous wastage in a series of 12 adolescent females . The patients who presented to our outpatient adole scent clinic ranged in age from 16 to 19 years, had a median menstrual gestational age of 6.0 weeks. and the majority were unaware that they were pregnant at the time of presentation. The onset of spontaneous vagin al bleeding occurred at a median men strual gestational age of 6.3 weeks and lasted an average of 8 .8 days. Eight patient s had one or more sexually transmitted diseases at their initial visit. Nine patients were prim igravidas and the other 3 had poor ob stetrical histories. Serial hCG titers were used to co nfirm the complete spontaneo us termination of the pregnanci es and to diagnose one ectopic pregnancy. No sig nificant chan ge in hematocrit s was observed. No cases were complicated by pelvic inflammatory disease . Dilatation and curettage (0 & C) was avo ided in all cases . A policy of aggressive serial hCG testing is strong ly recom mended to accurately diagnose very early pregnancy loss in ado lesce nt females; D & C has no role in their management.

Key Words. Adolescent pregn ancy- Ectopic preg nancyHuman chor ionic gonadotro pin-Pregnancy testingSpontaneous abort ion

Introduction The incidence of early spontaneous pregnancy loss has been previously reported by many investigators. ">' Address reprint requ ests to: Elaine E. Yordan, M.D ., Department of Pediatrics , Section of Adolescent Medi cine. Sai nt Francis Hospital and Med ical Ce nter , 114 Woodland Street, Hartford , CT 06 105 , USA Presented in part at the Thi rd Annua l Meet ing of the North American Society for Pediatric and Adolescent Gynecology held in Houston; TX, Oct. 1988 .

Most recently , Wilcox et al. 4 reported a total rate of pregnancy loss after implantation of 3 1%. The specific incidence of early pregnancy loss in the femal e adolescent population has not been rep orted . Th e radioimmunoassay of human chorionic go nadotropin (hCG) is able to detect hCG produ ct ion by the syncytiotrophoblast 6-8 days after conception.' We observed adolescent females who had very early clinically detectable pregnancies that ended in complete spontaneous abortion . We review our exper ience and suggest guidelines for the clinician in diagno sis, evaluation , and management of such cases .

Materials and Methods Over a 36-month period, positive pregnancy tests were obtained in 151 of the fem ale ado lescents who were patients in an ambulatory adolescent clinic. Of this group, 12 were diagnosed to have very ea rly spontaneous wastage of their pregnancies. Thi s observ ation was possible because of a policy that included the liberal use of pregnancy testing . An immunoenzymetri c assay for the semiquantitative determination of hCG in the urine (Tandem ICON II HCG, Hybritech Inc .. San Diego , CA ) was readily available in this cl inic for immedi ate pregnancy testing. The sensitivity of this assay for urin ary hCG concentrations is 20 mIU /rnl , and the spec ificity is rated by the manufacturer as 100%. The assay also allows for the distinction of positive results of less than 50 mIU Iml which is accomplished by comparing the positive reference zone in the test cylinder with the patient test zone. When a specimen produces a circular blue dot in the patient test zone, it is positive for the presence of heG . If the color intens ity of the blue dot in the pati ent test zone is less than the color intensity of the reference zone, the conc entration of hCG is less than 50 mIU Iml.

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Very Early Pregnancy Loss in Adolescents

Two categories of patients were considered as candidates for the immediate institution of a program of serial serum hCG testing: those with a weakly positive urine hCG test «50 mIU /ml, n = 6 patients) and those who demonstrated early complications of pregnancy such as bleeding, abdominal pain, or pelvic pain (n = 15 patients). An immunoenzymetric assay to detect hCG in the serum (Tandem-RHCG, Hybritech Inc.), was used to monitor the course of those pregnancies. The assays were calibrated against the World Health Organization's first International Reference Preparation. The sensitivity of this assay is 1.5-2.5 mID /ml. All the patients in this study had a complete gynecologic examination including bimanual pelvic examination and endocervical cultures for Neisseria gonorrhoeae (GC) (JEMBEC with Modified ThayerMartin Agar, BBL Microbiology Systems, Cockeysville, MD) and Chlamydia trachomatis (CT) (C. trachomatis Culture Confirmation Test, Syva Company, Palo Alto, CA). The results of yearly routine cervical cytologic screening and serum rapid plasma reagin (RPR) were reviewed for each patient and updated as needed. A culture for herpes simplex virus (HS V) (Primary Rabbit Kidney Cells, Viromed Labs, Minnetonka, MN) and a RPR were done if any genital lesion was found. In addition, a RPR was obtained if any other sexually transmitted disease (STD) was diagnosed. Vaginal discharge was evaluated in the clinic by wet prep. The hemoglobin (Hgb) and hematocrit (Hct) of all of the 12 patients were monitored. Erythrocyte sedimentation rate (ESR) was obtained in the patients who had positive endocervical cultures for GC and/or CT. Ultrasound studies were not routinely done except in 2 cases that had clinical features that prompted these studies. STDs were treated according to previously published standards. 6 The blood type and Rh of each patient were documented. Patients who were Rh negative were treated with Rho(D) Immune Globulin (Human) (RhoGAM, Ortho Diagnostic Systems Inc., Raritan, NJ). The following case reports are representative of this study population and highlight the management techniques.

Case Reports Case #1 A 19-year-old black female who had never been pregnant presented to the adolescent clinic requesting contraception. She had a history of regular menses with her last menstrual period on June 16th • She had a 5day episode of light vaginal bleeding on June 24 th • Suspicion was raised because of the unusual, irregular

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vaginal bleeding. A urine pregnancy test was weakly positive. The patient denied vaginal discharge, pelvic pain, or current vaginal bleeding. Her pelvic examination was normal. She had a positive endocervical culture for GC, a negative endocervical culture for CT, and a nonreactive RPR. She was treated for Gc. Her Papanicolaou smear was benign yet showed the presence of trichomonads and inflammation. Her blood type was 0 positive. An initial serum hCG titer was 89 mID /ml. The following day, she began light vaginal bleeding and a repeat hCG titer was 27 mIU /ml. After 4 days of light vaginal bleeding, she had a hCG titer of 0 mIU /ml. Her Hct was 36.4% and her ESR was 11 mm/hour.

Case #2 A 19-year-old sexually active black female who used no contraception presented to the adolescent clinic requesting a pregnancy test. Her chief complaint was 24 hours of vaginal bleeding and cramps 5 weeks after a normal menstrual period. A urine pregnancy test was done and found to be positive. Her past obstetrical history included one first trimester elective termination of pregnancy and the delivery of a 25-week premature infant. Her pelvic examination was normal and a small amount of blood was present in the vagina. The endocervical culture for GC was positive and for CT it was negative. She was treated with appropriate antibiotics. The RPR was negative. Her Hct was 41.1 % and the ESR was 6 mm/hour. Her blood type was 0 positive. An initial serum hCG titer was 1201 mIU/ml. Forty-eight hours later, with light vaginal bleeding, her hCG titer was 318 mID/ml. At 96 hours, with continued light vaginal bleeding, her hCG titer was 128 mIU/ml. After a total of 8 days, the light vaginal bleeding had completely stopped and her hCG titer was 8.2 mIU/ml.

Case #3 A 19-year-old sexually active black female who used no contraception presented to the adolescent clinic with a history of "vaginal spotting" that began 5 weeks after a normal menstrual period. A urine pregnancy test was positive. Her past medical history included two episodes of salpingitis, and two positive endocervical cultures for Gc. Her pelvic examination was normal and non tender with a scant amount of blood in the vagina. Her endocervical culture for GC was positive and she was appropriately treated. The endocervical culture for CT was negative. Her Hct was 40% and the ESR was 2 mm/hour. The blood type was B positive. An initial serum hCG titer was 334 mIU/ml. At 48 hours, her hCG titer was 284 mIU/ ml. At 96 hours, the hCG titer was 236 mIU /ml. The patient was unable to return to the clinic until 6 days

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Very Early Pregnancy Loss in Adole scents

later, at which time her hCG titer was 583 mIU/ml. Over the following 5 days, her hCG titers were 861 mIU Iml and 851 mIU Iml. A transabdominal pelvic ultrasound was inconclusive. Laparoscopic examination showed a 2 x I ern cystic dilatation of the right fallopian tube . An ectopic pregnancy was diagnosed and a salpingostomy was performed.

Results Over a 3-year period, 12 adolescent females ages 1619 years, who had very early spontaneous wastage of their pregnancies, were treated. The median menstrual gestational age of these pregnancies was 6 .0 weeks at the time of presentation . All the patients developed spontaneous vaginal bleeding and this occurred at a median menstrual gestational age of 6 .3 weeks . The vaginal bleeding lasted an average of 8.8 days. Two patients knew they were pregnant at the time of initial presentation to the clinic, 5 presented requesting pregnancy tests, and the other 5 had chief complaints of vaginal discharge, vulvar lesions , contraception, pediculosis pubis, and menstrual abnormality. Three patients had positive endocervical cultures for GC, I had condyloma acuminatum, I had GC isolated from the endocervical canal and Trichomonas vaginalis (trich) on wet mount , and I had CT isolated from the endocervical canal, genital HSV, and trich on wet mount. One patient had both GC and CT isolated from the endocervical canal, pediculosis pubis, and Gardnerella vagina lis on wet mount. Nine patients were primigravidas and the other 3 had poor obstetrical histories. Included among these were a spontaneous abortion at 16-weeks gestation, the delivery of a 25-week premature infant, and the delivery of a premature infant with Trisomy 13. The initial serum hCG titers were all below 340 mIU Iml except in 3 patients; they had initial titers of 3,839 mlU/ml , 1,476 mIU Iml , and 1,20 I mlU Iml, respectively. Sonographic evaluation was used in 2 cases . The patient with the titer of 3,839 mIU/ml had transabdominal and transvaginal pelvic ultrasound findings consistent with a complete spontaneous abortion. This was substantiated with a hCG titer decrease to 263 mIU I ml over a span of just 5 days. The other patient who had a pelvic ultrasound had the ectopic pregnancy described in Case #3 . None of the patients had blood loss that exceeded a normal menstrual period for them. No significant change in Hcts was observed and there was spontaneous and complete cessation of all vaginal bleeding. D & C was avoided in all cases . Despite the fact that so many of the patients had STDs, standard therapy appeared to be sufficient in preventing pelvic inflammatory disease. There was no case of an

adverse sequela from this conservative management. In fact, 7 of these patients have had subsequent pregnancies and prenatal care (Table I).

Discussion Implantation of the blastocyst occurs at approximately 7 days after ovulation . ' At this time , hCG from the syncytiotrophoblast begins to reach the maternal circulation in detectable amounts. 5 Human chorionic gonadotropin has been found in maternal plasma and urine as early as 6-8 days after conception. " Wilcox et a1.4 defined a spontaneous pregnancy as elevations of hCG produced by a blastocyst. A pregnancy loss can, thereby, be considered to encompass the events that lead to the disappearance of detectable amounts of hCG in the maternal peripheral serum or urine. Pregnancy loss can result from the failure of the placentation process, abnormal differentiation of the early cell mass, failure of the corpus luteum, aberrant fetal growth, genetic abnormalities, the influence of toxic environmental factors, or infectious agents ." In 1972, Vaitukaitis et al." first reported the development of a radioimmunoassay using antiserum to the beta-subunit of hCG in samples containing both human pituitary luteinizing hormone and hCG . Since that time, many advancements in the technology of measuring hCG have been made. 10 The widespread availability of this technology allows the clinician to make very early, accurate diagnoses of normal and abnormal pregnancies . In a normal growing pregnancy, the doubling time of hCG concentrations has been estimated by various investigators to be between 1.4 and 3.5 days, reaching a peak after 60-80 days .t" Mean plasma concentrations of hCG reach between 50 and 250 mIU I ml at the time of the first missed menstrual period. 12 The elimination of hCG is determined by a biphasic half-life with a first component of 5-9 hours followed by a slower component of 22-32 hours. 13 The devitalization of trophoblastic tissue in a spontaneous abortion is responsible for a relatively rapid disappearance of hCG. 13 Numerous investigators have observed that serum hCG titers that do not conform to those previously established parameters of hCG activity are highly characteristic of ectopic pregnancies. 14 - 16 Nyberg et a1.17 reported reliable transabdominal sonographic signs that identified intrauterine gestational sacs where serum hCG titers were at least 1,800 mIU Iml. As most of the serum hCG titers in our patients were well below this discriminatory zone, ultrasound was not performed. However, we do recommend transabdominal and/or transvaginal sono-

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Very Early Pregnancy Loss in Adolescents

Table 1. Patients Who Had Very Early Spontaneous Wastage of Pregnancies Age (yrs)

OB History

Chief Complaint

1 2 3'

19 19 19

G1POOOO G3P0111 G1POOOO

Contraception Pregnancy test Pregnancy test

6.0 5.4 6.3

6.1 5.3 5.3

4 8 16

4

19

G2POOIO

5.1

5.1

5

16

G1POOOO

Vaginal discharge Vulvar lesions

4.9

6

17

G1POOOO

Pregnancy test

7 8

17 18

G1POOOO G1POOOO

9 10

18 19

G4P0l21 GIPOOOO

11

16

GIPOOOO

12

16

GIPOOOO

Pregnancy test Pregnancy counseling Pregnancy test Pregnancy and vaginal bleeding Unusual menses Pediculosis Pubis

Case

Initial Menstrual Duration Menstrual hCG Titer Gestational Age Gestational Age of at Time of at Time of Onset Vaginal (mIU/ml) Presentation of Vaginal Bleeding (weeks) Bleeding (days) (weeks)

Hct

ESR

(%)

(rnm/hr)

89 1201 334

36.4 41.1 40.0

11 6 2

GC, Trichomonas GC GC

15

142

36.6

14

GC

6.6

4

>50

35.7

8

4.4

5.0

7

25

40.9

3.4 9.7

4.4 10.6

7 11

16 3839

37.9 35.9

17.0 b 8.4

17.3 b 8.0

14 7

1476 13

36.3 39.4

7.0

6.4

8

120

39.5

6.0

6.4

5

182

36.6

STD

CT,HSV Trichomonas Condylomata Acuminatum

20

Trichomonas

10

GC, CT, Pediculosis Pubis Gardnerella

'Ectopic pregnancy "Patient unsure of last menstrual period

graphic evaluation to confirm intrauterine pregnancy when serum hCG titers have reached an appropriate discriminatory zone for each technique, or display a pattern suggestive of ectopic pregnancy. The frequency of STDs in our patient group raises the possibility that the pregnancies were lost because of damage caused by an infectious agent. Of the other 139 patients with positive pregnancy tests, only 30 were diagnosed as having one or more STDs. GC is a known cause of spontaneous abortion in the first trimester. 18 As gonococcal transport via attachment to spermatozoa has been demonstrated, this mechanism could be responsible for infection as early as the time of conception." HSV has also been associated as a causative agent of spontaneous abortion in the first trimester. 20 At this time, it is unknown if CT infection can cause spontaneous abortion in the first trimester. 18.20.21 Adolescent pregnancy and its medical and psychosocial complications are issues of great concern to health care practitioners treating teenagers. The indications for pregnancy testing in female adolescents should be expanded beyond those indications generally applied to adult females. Most physicians testing for pregnancy would test for symptoms of amenor-

rhea, irregular vaginal bleeding, gastrointestinal disturbances, or breast tenderness. Pregnancy should be suspected in any adolescent whether she admits to being sexually active or not. Pregnancy should also be considered in female adolescents with fatigue, abdominal pain, urinary tract symptoms, backache, or STDs. We must consider pregnancy in such instances when the female adolescent is displaying signs of depression. Pregnancy should be suspected when there is acting out behavior such as truancy, running away from home, or substance abuse. Reluctant to admit to sexual activity or fearing pregnancy, the adolescent female will often present with a chief complaint that avoids these issues, or with no chief complaint at all. With liberal indications for pregnancy testing, we identified a group of patients whose pregnancies and their eventual wastage may have gone undiscovered. By using serial serum hCG titers, we were able to recognize that the loss of these pregnancies was complete. Within 4 weeks, all the patients had resumption of normal menstrual function. The shortest individual long-term follow-up has been 7 months. None of the patients have had any resultant gynecologic complications. None of our patients were subjected to an inappropriate D & C. We also observed a high degree

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Very Early Pregnancy Loss in Adolescents

of interest and compliance on the part of our adolescent patients as they too were interested in the outcomes of their pregnancies and their general state of health. The patients' emotional reactions to the experience varied from indifference to expressions of grief and a sense of loss. The early diagnosis of the ectopic pregnancy was also made possible by the liberal use of serial serum heG titers. Many studies of normal reproduction refer to "chemical pregnancies," "beta-hCG pregnancies," and "occult pregnancies. ,,3.22 We observed very early spontaneous abortions in a population of adolescents that all shared a series of common characteristics: 1) rapid disappearance of initially low levels of hCG. 2) associated vaginal bleeding similar to or indistinguishable from a menstrual period. 3) no 0 & C was required, and 4) all the patients reported the occurrence of a normal menstrual period within 1 month. Long-term follow-up between 7 and 36 months has confirmed continued normal menstrual function and fertility. The incidence of very early spontaneous abortion in adolescents is unknown. We believe that most clinicians can diagnose. evaluate and manage such cases by following the guidelines described. When adult women are studied, the rate of spontaneous abortion is greater than 30%.4 It is reasonable to hypothesize that very early spontaneous abortions in adolescents occur with equal frequency. Further investigation and careful screening of female adolescent patients will be necessary to provide additional insight into this issue. Acknowledgments. We wish to thank Burton V. Caldwell. M. D., Ph. D., for his assistance in the preparation of this manuscript.

References I. French F. Bierman J: Probabilities of fetal mortality Public Health Rep 1962; 77: 835 2. Roberts C, Lowe C: Where have all the conceptions gone? Lancet 1975; 1:498 3. Edmonds D, Lindsay K. Miller J, et al: Early embryonic mortality in women. Fertil Steri! 1982; 38: 447 4. Wilcox A. Weinberg C, O'Connor J, et al: Incidence of early loss of pregnancy. N Engl J Med 1988; 319: 189 5. Steier J, Sandvei R, Myking 0: Human chorionic gonadotropin in early normal and pathologic pregnancy. Am J Obstet Gynecol 1986; 154: 1091 6. Centers for Disease Control: Sexually transmitted diseases treatment guidelines 1985. MMWR (Suppl 4) 1985; 34:1

7. Fishel S, Edwards R, Evans C: Human chorionic gonadotropin secreted by preimplantation embryos cultured in vitro. Science 1984; 223:816 8. Bennett M, Edmonds D (eds): Spontaneous and Recurrent Abortion. Oxford, Blackwell Scientific Publications, 1987, pp 2-5 9. Vaitukaitis J, Braunstein G, Ross G: A radioimmunoassay which specifical!y measures human chorionic gonadotropin in the presence of human luteinizing hormone. Am J Obstet Gynecol 1972; 113:751 10. Vaitukaitis J: Practical considerations of specific hCG assays for clinical use. Ligand Rev (Suppl 2) 1981; 3:45 11. Pittaway K, Reish R, Wentz A: Doubling times of human chorionic gonadotropin increase in early viable intrauterine pregnancies. Am J Obstet Gyneco1 1985; 152:299 12. Lenton E. Neal L. Sulaiman R: Plasma concentrations of human chorionic gonadotropin from the time of implantation until the second week of pregnancy. Fertil Steri! 1982; 37: 773 13. Steier J, Bergsjo P, Myking 0: Human chorionic gonadotropin in maternal plasma after induced abortion, spontaneous abortion, and removed ectopic pregnancy. Obstet Gynecol 1984; 64: 391 14. Holman J, Tyrey E, Hammond C: A contemporary approach to suspected ectopic pregnancy with use of quantitative and qualitative assays for the l3-subunit of human chorionic gonadotropin and sonography. Am J Obstet Gynecol 1984; 150: 151 15. Cartwright P, DiPietro D: Ectopic pregnancy: changes in serum human chorionic gonadotropin concentration. Obstet Gynecol 1984; 63: 76 16. Romero R, Kadar N, Copel J, et al: The value of serial human chorionic gonadotropin testing as a diagnostic tool in ectopic pregnancy. Am J Obstet Gynecol 1986; 155:392 17. Nyberg D, Filly R, Mahony B, et al: Early gestation: correlation of HCG levels and sonographic identification. AJR 1985; 144:951 18. McFalls J Jr, McFalls M: Disease and Fertility. Orlando. Academic Press, 1984, p 381 19. Toth A, O'Leary W, Ledger W: Evidence for microbial transfer by spermatozoa. Obstet Gynecol 1982; 59:556 20. Gronroos M, Honkonen E, Punnonen R: Cervical and serum IgA and serum IgG antibodies to Chlamydia trachoma tis and herpes simplex virus in threatened abortion: a prospective study. Br J Obstet Gynecol 1983; 90: 167 21. Quinn P, Petrie M, Barkin M, et al: Prevalence of antibody to Chlamydia trachomatis in spontaneous abortion and infertility. Am J Obstet Gynecol1987; 156:291 22. Jones H Jr, Acosta A, Andrews M, et al: What is a pregnancy? A question for programs of in vitro fertilization. Ferti! Steril 1983; 40: 728