The Role of GnRH Agonist Therapy and Hysterosalpingography (HSG) in Diagnosing and Treating Tubal Factor Infertility

A 27-year-old woman and her 31-year-old husband, presented with primary infertility for three years. The female complained of irregular, but prolonged and painful periods (dysmenorrhea) and painful coitus (dyspareunia). Magnetic resonance imaging (MRI) finding: An MRI revealed a cystic mass at the posterior cervical lip. Transvaginal sonography (TVS) findings: TVS revealed a cystic lesion with ground-glass echogenicity, measuring 19 × 12.5 mm, in the posterior cervical lip suggestive of cervical endometriosis. Hormonal investigation of female: As part of a fertility workup, the patient’s antral follicle count (AFC), anti-Müllerian hormone (AMH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prolactin levels were checked. All the hormone levels were normal as displayed in Table 1 , thus excluding hormonal imbalance as the cause of infertility. Hormonal profile of female The male partner was advised to have a fertility work-up, which included semen analysis, as well as sperm DNA fragmentation assay. Semen analysis showed that the sperm concentration, progressive motility, and sperm morphology were within the normal range as shown in Table 2 . Also, in the sperm DNA fragmentation test, the DFI mean was 12%, which is considered low. Therefore, all the semen parameters and sperm DNA integrity were within the normal range, thus excluding male factor infertility. Hormonal profile of male A 27-year-old woman with a history of infertility and prolonged menstruation was treated by the use of hormonal therapy, diagnostic assessment, and in vitro fertilization (IVF) to address her endometriosis and achieve pregnancy. The treatment was initiated by the administration of triptorelin acetate (3.75 mg) on day 3 of the patient’s menstrual cycle, and this was followed by another injection 28 days later. This GnRH agonist was used to inhibit the ovary function and cease the chronic vaginal bleeding due to endometriosis. It is an injectable drug that can downregulate the pituitary gland, hence decreasing the stimulation of the ovaries and offering symptomatic relief. After rectifying her menstrual problems, a hysterosalpingography (HSG) was conducted and the test showed that she had bilateral hydrosalpinx, whereby the tubes are filled with fluid, preventing the eggs from reaching the uterus and hence, preventing conception. Because of the bilateral hydrosalpinx, the patient was counseled to go for IVF as the most suitable technique to help her conceive. To suppress the natural hormonal cycle, triptorelin acetate in the dose of 0.8 mg was started in the mid-luteal phase of the menstrual cycle. After 14 days of treatment, the size of the cystic lesion in the cervix, which was 19 × 12.5 mm, decreased to 9 × 6 mm; the patient’s serum CA125 level, which was elevated due to endometriosis, decreased to 31.3 U/mL. After this stabilization, gonadotropin stimulation was begun to further develop the ovarian follicles. When three or more dominant follicles ≥17 mm were seen on ultrasound, final maturation of oocytes was induced with human chronic gonadotropin (hCG) and ovum pickup was done post 36 hours. A total of 14 oocytes were retrieved, out of which 10 oocytes were successfully fertilized. Due to the chance of ovarian hyperstimulation syndrome (OHSS), all embryos were cryopreserved for future use, including three cleavage-stage embryos and four blastocysts. After six months of the IVF cycle, triptorelin acetate (3.75 mg) was administered again in the mid-luteal phase, and hormone replacement therapy was initiated to develop the endometrium for embryo transfer. A few days after hormone replacement therapy, one blastocyst was thawed and transferred as presented in Figure 1 , which successfully led to an intrauterine pregnancy. Transferred blastocyst The patient was advised to revisit the clinic for a β-hCG test after two weeks of the embryo transfer. The β-hCG level measured 256 mIU/mL, indicating successful conception. Due to the diagnosis of placenta previa in the third trimester, the patient was advised to visit the clinic for a follow-up every month to check for the baby’s progress. The patient was advised to rest and engage in moderate physical activity to prevent further complications.

Infertility may be described as the inability to conceive for at least one year without the use of any birth control measures. It is found that about 85% of infertile couples have some clear and treatable cause. The three major factors of infertility include ovulatory abnormality, male infertility factor, and tubal factor. The other five percent of couples who are infertile are considered to have “unexplained infertility.” Some of the factors that can hinder fertility include smoking and obesity among others. Ovulatory disorders are the cause of 25% of infertility cases; 70% of all women with anovulation have polycystic ovary syndrome.[ 1 ] Obesity is associated with conditions, such as ovulatory dysfunction, poor reproductive health in women with polycystic ovary syndrome (PCOS), and low fecundity in women with normal menstrual cycles. It impacts the quality of oocytes and early embryonic development, impairs the mitochondria, and causes chronic low-grade inflammation. Obesity also affects the endometrium, hence increasing their chances of getting complications, such as miscarriage, stillbirth, and preeclampsia.[ 2 ] Endometriosis is a chronic inflammatory disease that is characterized by the presence of endometrial-like tissue outside the uterus. Currently, there is no cure and the treatment is only symptomatic by medical or surgical intervention, but they do not provide a cure or long-term satisfaction for all patients.[ 3 ] Endometriosis is a chronic, multisystem disorder that has the potential to negatively impact female fertility and overall quality of life. The disease is primarily driven by two key pathophysiologic mechanisms: chronic inflammation and hormonal dependence. Altogether these factors contribute to the polyclonal clinical nature of endometriosis. Endometriosis is estimated to affect 10% of women of reproductive age, of which about one-third experience infertility. Also, it is estimated that up to 50% of women struggling with infertility have endometriosis.[ 4 ] Approximately one-third of women with the condition are asymptomatic. When symptomatic, pelvic pain is the most common complaint. Other reported symptoms include painful urination (dysuria), blood in urine (hematuria), lower back pain, pain with bowel movements (dyschezia), irregular bleeding, pain during intercourse (dyspareunia), and painful menstruation (dysmenorrhea).[ 5 ] Dysmenorrhea is normally expressed as painful cramps in the lower abdominal region and may vary in intensity and the symptoms include nausea, vomiting, loss of appetite, fatigue, diarrhea, headaches, restlessness, insomnia, and fainting. Primary dysmenorrhea is mainly attributed to an increase in the levels of prostaglandins and leukotrienes.[ 1 ] Hydrosalpinx, caused by the blockage of the infundibulum and accumulation of fluid within the ampullar lumen, may be confirmed through ultrasonography (USG) or HSG. Hydrosalpinx diagnosed by ultrasound in infertile women ranges from 10 to 13%, while that diagnosed with hysterosalpingography or laparoscopy approached 30%. This condition affects women of childbearing age and has been linked with low pregnancy chances while taking fertility treatments.[ 6 ]

The present case shows the correct approach to a challenging case of infertility related to endometriosis and bilateral hydrosalpinx. The use of hormonal suppression with a GnRH agonist, followed by IVF and embryo cryopreservation, proved to be an effective strategy. The proper management of the endometrium through replacement therapy and correct timing of the blastocyst transfer led to a successful pregnancy. The patient’s case describes the importance of employing an individualized treatment model for endometriosis and tubal factor infertility to achieve a favorable outcome. This case also emphasizes the need for expectant management during pregnancy, and the need for frequent follow-up to ensure complications, such as placenta previa, is well managed. The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. There are no conflicts of interest.

The present case highlights the approach toward infertility in a woman with endometriosis and bilateral hydrosalpinx by the use of hormonal therapy, IVF, and embryo freezing. Endometriosis, which has been known to cause fertility problems through mechanical means, like adhesions, inflammation, or cyst development, was one of the challenging problems in this patient. Bilateral hydrosalpinx rendered the situation worse because fluid-filled fallopian tubes reduce the likelihood of conception, both naturally and through ART. GnRH agonist, triptorelin acetate, provided a major control in the management of the patient’s endometriosis and submission to IVF. Triptorelin acetate suppressed ovarian activity and decreased the size of the cysts, and the level of serum CA125, the indicator of endometriosis activity. Hormonal suppression of ovarian function, which is done with GnRH agonists, is the common treatment strategy for endometriosis as it helps lesions to decrease in size and reduces inflammation that could potentially negatively affect fertility. The decision to continue with IVF after the diagnosis of bilateral hydrosalpinx was appropriate since the hydrosalpinx could greatly affect the natural conception rate. IVF avoids this by replacing the fallopian tubes as a place for fertilization to occur outside the body, and the embryos to be transferred directly into the uterus. In this patient’s case, the GnRH agonist long protocol facilitated the regulation of ovarian stimulation and yielded an optimum number of oocytes. The collection of 14 oocytes, of which 10 were fertilized, demonstrates the success of controlled ovarian hyperstimulation in increasing fertility rates even with endometriosis. Another consideration made in this treatment was the use of frozen embryos rather than fresh embryo transfer because of OHSS risk. This prevented creating a fresh transfer, gave the ovaries some rest, and prepared the endometrial for implantation at a later date. There was also the application of hormone replacement therapy to prepare the endometrium for the transfer of the embryo to provide the appropriate environment for implantation. In this case, the transfer of one blastocyst 14 days after HRT resulted in a successful intrauterine pregnancy, which underlined the necessity of accurate endometrial preparation to achieve satisfactory results in patients with endometriosis. The present case demonstrates the usefulness of combined management of infertility in cases with endometriosis and hydrosalpinx. It also became possible by hormonal treatment, IVF, and proper planning of embryo transfer. In their study, Aina Delgado-Morell et al .[ 7 ] observed that even though IVF has significantly improved the conception rate among people with fertility issues attributable to tubal blockage, the existence of hydrosalpinx has been found to have adverse effects on IVF results. A study done by Laura Benaglia et al .[ 8 ] pointed out that the occurrence of placenta previa is considerably higher in women with endometriosis than in women without the disease, which means that women with endometriosis are at a greater risk of experiencing this complication. According to Robert M. Silver, placental disorders, for instance, the placenta previa, are typically associated with vaginal bleeding in the second half of the pregnancy. These conditions are major risk factors for severe fetal and maternal morbidity and mortality.[ 9 ] According to the study conducted by Jifan Tan et al. ,[ 10 ] it was found out that HSG is a useful tool in diagnosing tubal pathology in infertility patients. HSG is a highly affordable test with good predictive capacity as a diagnostic modality for tubal factor infertility.