Navigating Ovarian Dysgenesis: Primary Ovarian Insufficiency with Breakthrough Bleeding Case

Abstract

This is a case report of a 17-year-old Taiwanese female with a karyotype of 46 XX whose diagnosis was confirmed as ovarian dysgenesis and tentatively diagnosed as uterine agenesis presenting with primary amenorrhea and delayed puberty. Initial hormonal evaluations revealed high levels of FSH and LH that are compatible with primary ovarian insufficiency, and imaging studies indicated the absence of a uterus. The patient had been started on hormonal replacement therapy to manage her hormonal deficiency. This patient, surprisingly, developed breakthrough bleeding at one month of HRT, although this is not characteristic in any primary ovarian insufficiency or uterine agenesis case. Of course, this particular case scenario pushes home the diagnostic challenges with Mullerian anomalies, difficulties in image interpretation, and also caution required in managing patients diagnosed with this condition. In addition, it brings out the serious psychological impact that these conditions entail, compelling a multidisciplinary approach addressing the medical and emotional components of care in adolescent patients.

Introduction

Most cases of the diagnosis of primary amenorrhea and delayed puberty among adolescent girls are very difficult because the conditions may be due to several anomalies in the gynecologic region. The two may include uterine agenesis and ovarian dysgenesis, both of which are highly significant for reproductive health as well as psychological impacts. Uterine agenesis or MRKH syndrome is a congenital condition where the uterus is absent or undeveloped in a patient. Ovarian dysgenesis is a term used to describe incomplete or improper ovarian development, and this term has been associated with primary ovarian insufficiency, also known as premature ovarian failure.

This may be accompanied by an evaluation of the HPO axis and hormonal studies to evaluate ovarian function in the case of primary amenorrhea. On the other hand, the diagnosis of Mullerian agenesis, with uterine agenesis included, relies on imaging techniques, such as ultrasound and MRI, which may be very challenging in an adolescent. The psychological impact on the patient and her family as a result of these diagnoses can also be tremendous.

Here we report a case study of a 17-year-old Taiwanese female patient who was diagnosed with ovarian dysgenesis and was tentatively diagnosed to have uterine agenesis with 46 XX karyotype. The patient presented with unusual breakthrough bleeding just one month after initiating hormonal replacement therapy. This case presentation shows the complexity of diagnosing and managing primary ovarian insufficiency and the psychological impact of gynecologic anomalies.

Case Presentation

Patient History and Initial Presentation

A 17-year-old Taiwanese female with concerns for primary amenorrhea and delayed puberty was referred to the reproductive endocrinology clinic. She had never had an onset of menstruation and had little in the way of breast development. She did have some occasional lower abdominal discomfort but had no cyclical pain or menstrual-like symptoms. She did not have a family history of gynecologic or genetic disorders. In the psychosocial history, she was noticed to have increased distress over being delayed into puberty compared with her friends, and she was anxious regarding her reproductive health given her peers.

Physical examination revealed Tanner II breast development and Tanner IV pubic hair. Her height and weight were appropriate for her age and otherwise, there were no abnormal physical findings.

Initial Diagnostic Workup

The initial workup for primary amenorrhea in this patient consisted of hormonal evaluations, which revealed increased levels of FSH and LH that were consistent with primary ovarian insufficiency. Estradiol was low, further pointing to ovarian failure. To further explore the possibility of an underlying structural anomaly, imaging studies were ordered.

Ultrasound of the pelvis was without evidence of a recognized uterus. Therefore, this put the tentative diagnosis as uterine agenesis. Magnetic resonance imaging showed there was no recognizable uterine structure, however, revealed small rudimentary ovarian tissue. Karyotyping was done in order to check for chromosomal abnormalities. A normal 46 XX karyotype gave no support for Turner syndrome or any other form of chromosomal abnormality typically associated with ovarian dysgenesis.

Consequently, a diagnosis was rendered for the patient with primary ovarian insufficiency resulting from ovarian dysgenesis as well as probable uterine agenesis.

Initiation of Hormonal Replacement Therapy

To treat the patient's hormonal deficiency and stimulate further sexual maturation, HRT was initiated. A regimen of estrogen was prescribed to stimulate breast development and overall health. The combination of estrogen and progestin was administered to follow the natural cycle of menstruation and prevent potential endometrial hyperplasia if any residual uterine tissue was present.

The patient was much counseled about the goals of therapy and also apprised of breakthrough bleeding, which would most likely occur after 2 to 3 years of HRT. Being diagnosed with uterine agenesis tentatively, the expectation would be minimal or no breakthrough bleeding.

Unusual Breakthrough Bleeding After One Month

After one month of HRT, the patient reported experiencing unexpected breakthrough bleeding. She described the bleeding as light but persistent for several days, resembling a light menstrual period. Given the initial diagnosis of uterine agenesis, this development was unexpected and raised concerns about the accuracy of the imaging findings.

The patient returned for further evaluation. A repeat pelvic ultrasound was performed, which again failed to identify a clear uterine structure, but small residual Mullerian structures could not be entirely ruled out. The presence of breakthrough bleeding prompted further consideration of the possibility that a small, functionally responsive endometrial remnant may have been overlooked during the initial diagnostic process.

The patient’s bleeding subsided spontaneously, and her HRT regimen was adjusted to a lower estrogen dose to minimize the risk of further bleeding. She was reassured that this breakthrough bleeding did not indicate a serious complication but rather highlighted the complexity of diagnosing uterine anomalies.

Discussion

Diagnostic Challenges in Uterine Agenesis

Diagnosing Mullerian anomalies such as uterine agenesis can be particularly challenging due to the variability in the development of residual Mullerian structures. While MRI is considered the gold standard for identifying uterine anomalies, small or underdeveloped uterine tissue can sometimes escape detection, particularly in young patients. In this case, despite imaging studies suggesting uterine agenesis, the patient’s breakthrough bleeding raised the possibility of residual functional endometrial tissue.

The presence of ovarian dysgenesis complicated the diagnostic picture further. Ovarian dysgenesis is often associated with primary ovarian insufficiency, leading to elevated FSH and LH levels and diminished estradiol production. This hormonal profile typically results in a lack of menstrual periods, making the occurrence of breakthrough bleeding highly unusual. However, in rare cases, small amounts of functional ovarian or endometrial tissue may persist, leading to unexpected bleeding episodes once estrogen therapy is introduced.

Psychological Impact of Gynecologic Anomalies

The psychological burden associated with a diagnosis of primary ovarian insufficiency and potential uterine agenesis cannot be overstated. Adolescents with primary amenorrhea often experience significant distress over their delayed pubertal development, which can exacerbate feelings of social isolation and anxiety. The possibility of infertility can have a profound impact on a young woman’s emotional well-being, particularly when the diagnosis is confirmed at such a formative stage of life.

In this case, the patient’s anxiety was compounded by the initial diagnosis of uterine agenesis, which indicated that future pregnancy would be impossible without advanced reproductive technologies such as surrogacy. Breakthrough bleeding after HRT initiation added another layer of uncertainty, further heightening the patient’s psychological distress.

Comprehensive counseling and psychological support are essential components of managing adolescent patients with gynecologic anomalies. In addition to addressing the physical aspects of the diagnosis, healthcare providers must offer compassionate care and emotional support to help patients cope with the emotional challenges that accompany these diagnoses.

Conclusion

This case of a 17-year-old female with ovarian dysgenesis, primary ovarian insufficiency, and a tentative diagnosis of uterine agenesis highlights the complexities involved in diagnosing and managing gynecologic anomalies in adolescent females. The unintended breakthrough bleeding on day 30 after just one month of hormonal replacement therapy underscores a careful need for a diagnostic evaluation and consideration of residual Mullerian structures even in cases of presumed uterine agenesis.

Much more studies need to be done to establish the interrelation between ovarian dysgenesis and HRT with breakthrough bleeding in patients with Mullerian anomalies. Even this case draws attention to the psychological implications of gynecologic diagnoses for young patients, thus calling for multidisciplinary care based on both medical support and emotional support.

References

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