In vitro fertilization-assisted pregnancy combined with high-intensity focused ultrasound treatment in patients with endometriosis and adenomyosis with successful pregnancy: a case report

Abstract

Background

High-intensity focused ultrasound ablation has emerged as a noninvasive therapeutic option for adenomyosis of the uterus. We studied a female with infertility patient to explore the application of in vitro fertilization combined with high-intensity focused ultrasound treatment in patients with endometriosis complicated by adenomyosis.

Case presentation

A retrospective analysis of a 30-year-old Han Chinese woman with infertility complicated by both endometriosis and adenomyosis was performed, including pregnancy achieved through in vitro fertilization, downregulation using a gonadotropin-releasing hormone agonist, high-intensity focused ultrasound treatment and final pregnancy outcomes. The patient successfully conceived following the combined application of high-intensity focused ultrasound treatment and downregulation using a gonadotropin-releasing hormone agonist, with an intrauterine pregnancy confirmed in June 2025 and appropriate fetal development.

Conclusion

The combined application of downregulation using a gonadotropin-releasing hormone agonist and high-intensity focused ultrasound treatment represents a promising therapeutic strategy for patients with infertility with concurrent endometriosis and adenomyosis. Nevertheless, prospective multi-centre studies remain essential to validate the long-term efficacy and safety profiles.

Background

Endometriosis affects approximately 11% of women [1]; it is a hormone-dependent disease with a poorly understood etiology and pathogenesis, and its primary symptoms include chronic pain and infertility [1, 2]. An increasing amount of evidence indicates that hormonal and immune factors jointly activate the local inflammatory microenvironment, thus promoting the persistence of endometriosis [1]. The prevalence of adenomyosis in patients with endometriosis is as high as 90%, and adenomyosis is a major contributor to infertility associated with endometriosis [3]. Estimates indicate that, without medical intervention, 50% of women with mild endometriosis become pregnant, 25% of women with moderate endometriosis become pregnant, and only a small proportion of women with severe endometriosis become pregnant [4]. For infertility associated with stage III/IV endometriosis, conservative (laparoscopic or laparotomic) surgery may provide benefits; furthermore, in vitro fertilization–embryo transfer (IVF–ET) represents an effective alternative for patients who fail to conceive post surgery or those with age-related fertility decline [5]. This case report describes a patient diagnosed with stage IV endometriosis and adenomyosis through surgical evaluation. After treatment of the adenomyosis lesion with high-intensity focused ultrasound (HIFU), the patient opted for in vitro fertilization (IVF) to achieve pregnancy and successfully conceived again.

Case presentation

General information

A 24-year-old Han Chinese woman was referred to our reproductive medicine center in September 2018 for primary infertility evaluation. She reported 24 months of unsuccessful attempts at conception despite regular unprotected intercourse, prompting consultation for assisted reproductive technology (ART) treatment.

The patient’s reproductive history was as follows: G0P0, and primary infertility for 2 years (since 2016) with regular unprotected coitus. Conventional hysterosalpingography performed in November 2017 demonstrated delayed spillage of contrast medium from the fimbrial ends of both fallopian tubes. In January 2018, the patient underwent concomitant hysteroscopic and laparoscopic surgery and was found to have stage IV pelvic endometriosis and adenomyosis. In April 2018, downregulation with gonadotropin-releasing hormone agonist (GnRH-a) was initiated in the outpatient clinic as a pretreatment for in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI).

The patient’s medical history and family history were unremarkable.

The patient’s menstrual and reproductive history were as follows: regular menstrual cycles, moderate flow and severe dysmenorrhea.

Examination

Physical examination: The physical examination results were as follows: height, 155 cm; weight, 46 kg; and body mass index (BMI), 19.2 kg/m².

Color Doppler ultrasound: Color Doppler ultrasound (July 2018) indicated the following: uterine size, 62 mm × 64 mm × 56 mm; myometrial characteristics: heterogeneous echotexture; and prominence: posterior uterine wall.

Hormone profile: The patient’s hormone profile (August 2018) was as follows: follicle-stimulating hormone (FSH) level: 4.25 mIU/mL; luteinizing hormone (LH) level: 1.91 mIU/mL; progesterone (PRGE) level: 0.20 ng/mL; estradiol (E2) level: 33.00 pg/mL; prolactin (PRL) level: 18.80 ng/mL; testosterone (TSTO) level: 17.55 ng/dL; and anti-Müllerian hormone (AMH) level: 4.44 ng/mL.

Diagnosis

Primary infertility

Stage IV pelvic endometriosis

Adenomyosis

Differential diagnosis

Secondary infertility: Secondary infertility is defined as the inability to establish a clinical pregnancy following 12 months or more of regular unprotected sexual intercourse in a woman with at least one previous clinical pregnancy (regardless of the outcome).

Pelvic venous congestion syndrome: Pelvic venous congestion syndrome (PVCS) is a condition of chronic pelvic pain (≥ 6 months) caused by dilated and refluxing ovarian/uterine veins. This condition is diagnosed by the exclusion of other pathologies and confirmed via invasive venography.

Treatment

November 2018: An ultralong protocol was employed with downregulation using triptorelin acetate (September to October 2018). Ovarian stimulation involved human menopausal gonadotropin (HMG) and recombinant human FSH (r-hFSH) (total of 1650 units), yielding nine transferable day-5 cleavage-stage embryos.

May 2019: The first frozen–thawed embryo transfer involved a single grade 3–5 blastocyst. Endometrial preparation involved a hormone replacement therapy (HRT) cycle with pretreatment with a GnRH-a (March to April 2019), resulting in a negative pregnancy outcome.

June 2019: Diagnostic hysteroscopy and endometrial biopsy were performed.

August 2019: GnRH-a therapy was performed.

October 2019: The second frozen embryo transfer involved a single grade-3 day-5 blastocyst. The endometrium was prepared with an HRT cycle, resulting in a confirmed clinical pregnancy.

June 2020: A caesarean section was performed at 36⁺⁶ weeks gestation owing to complete placenta previa and breech presentation, resulting in a live-born infant with no immediate complications.

October 2021: GnRH-a therapy was performed.

January 2022: A levonorgestrel intrauterine system (LNG-IUS) was inserted for the therapeutic management of dysmenorrhea.

June 2022: The LNG-IUS was removed owing to a lack of symptomatic improvement in dysmenorrhea.

December 2022: The third frozen embryo transfer involved a single day-5 3BB blastocyst. Endometrial preparation involved the combination of a GnRH-a (August to October 2022) with HRT, resulting in biochemical pregnancy.

July 2023: Laparoscopic left salpingectomy, right tubal ligation, hysteroscopy and endometrial biopsy were performed for hydrosalpinx.

December 2023: The fourth embryo transfer involved one thawed D5 2BC-grade blastocyst. The endometrial preparation protocol involved a GnRH-a regimen (July to November) with HRT. No pregnancy was achieved.

February 2024: The fourth embryo transfer involved two D5 3BC-grade blastocysts. The endometrial preparation protocol followed a natural cycle. No pregnancy was achieved.

May 2024: In the second IVF cycle, an ultralong protocol was employed with downregulation using triptorelin acetate, and ovarian stimulation was achieved via 2925 IU of combined HMG + rFSH. Embryo culture yielded three D6 blastocysts (4BC × 2, 3CB) and one D5 blastocyst (3BC).

June 2024: Real-time integrated ultrasound localization identified an anteverted uterus with a posterior wall lesion measuring 71 mm × 70 mm × 49 mm. Preoperative contrast-enhanced ultrasound revealed intralesional microvascular perfusion and HIFU ablation was performed for adenomyosis lesions. The mean treatment power was 301 W, and the sonication duration was 652 seconds (treatment was discontinued at 652 seconds following real-time contrast-enhanced ultrasound monitoring; treatment intensity, 495 seconds/hour; total acoustic energy, 196,300 J).

December 2024: The serum CA125 level was 32.00 U/mL. Doppler ultrasound revealed a decreased thickness of the posterior uterine wall. Pelvic magnetic resonance imaging (MRI) revealed radiographic regression of the posterior uterine wall lesion (Fig. 1).

Fig. 1.

Ultrasound and magnetic resonance images of uterine gland disease foci before and after HIFU treatment

December 2024: Hysteroscopic lysis of intrauterine adhesions was performed; the final diagnosis was mild intrauterine adhesions (IUAs).

January 2025: The fifth embryo transfer involved two day-5 blastocysts (3BC + 5BC). The endometrial preparation protocol involved sequential GnRH agonist pretreatment and HRT. A biochemically confirmed pregnancy was achieved.

Follow-up

January 2025: The serum beta-human chorionic gonadotropin (β-hCG) level was 428.56 mIU/mL, consistent with biochemical pregnancy.

June 2025: The Doppler ultrasound findings (Fig. 2) were as follows: an intrauterine gestational sac, fetal cardiac activity and appropriate fetal development for gestational age.

Fig. 2.

Color Doppler ultrasound performed during pregnancy

Discussion

This case demonstrates the successful application of IVF combined with HIFU treatment in a patient with endometriosis and adenomyosis. Following repeated IVF failure, the patient declined preimplantation genetic testing (PGT). With embryonic causes ruled out, we implemented a regimen of downregulation using a GnRH-a combined with HIFU to address the patient’s uterine pathologies. This approach ultimately resulted in a successful pregnancy. As a noninvasive modality, HIFU offers an emerging therapeutic alternative for patients with adenomyosis.

Endometriosis affects approximately 11% of women [1]; it is a hormone-dependent disease with a poorly understood etiology and pathogenesis, and its primary symptoms include chronic pain and infertility [1, 2]. An increasing amount of evidence indicates that hormonal and immune factors jointly activate the local inflammatory microenvironment, thus promoting the persistence of endometriosis [1]. The prevalence of adenomyosis in patients with endometriosis is as high as 90%, and adenomyosis is a major contributor to infertility associated with endometriosis [3]. Estimates indicate that, without medical intervention, 50% of women with mild endometriosis become pregnant, 25% of women with moderate endometriosis become pregnant and only a small proportion of women with severe endometriosis become pregnant [4]. For infertility associated with stage III/IV endometriosis, conservative (laparoscopic or laparotomic) surgery may provide benefits; furthermore, in vitro fertilization–embryo transfer (IVF–ET) represents an effective alternative for patients who fail to conceive post surgery or those with age-related fertility decline [5].

HIFU ablation has emerged as a noninvasive therapeutic option for adenomyosis of the uterus. This treatment is a valuable option for patients with adenomyosis who wish to preserve their fertility and who experience symptoms. HIFU operates by precisely targeting and delivering focused energy to specific lesion sites, leveraging thermal effects to induce protein denaturation, ultimately resulting in coagulative necrosis [6]. At 3, 6 and 12 months after HIFU treatment, the uterine volume reduction rates in patients with adenomyosis were 43.99%, 47.01% and 53.98%, respectively, and the symptom severity scores decreased by 55.61%, 52.38% and 57.98%, respectively [7]. Compared with HIFU treatment for adenomyosis, HIFU combined with GnRH-a treatment was more effective in reducing the uterine volume and adenomyosis lesion volume and relieving symptoms [8]. However, the therapeutic effect and recurrence rate after HIFU are related to the type of adenomyosis. For example, HIFU treatment for focal adenomyosis is better than that for diffuse adenomyosis because diffuse adenomyosis is large, has poorly defined boundaries and has a higher postoperative recurrence and reintervention rate [9]. Adenomyosis is classified as internal, external, intramural or full-thickness adenomyosis on the basis of MRI findings correlating adenomyotic lesions with endometrial and subserosal involvement [10]. Tailored strategies and parameters for different types of adenomyosis are employed in HIFU, but satisfactory therapeutic outcomes are consistently achieved [11]. The effect of HIFU treatment on dysmenorrhea and menorrhagia decreased over time, and the results after 6 months and 3 years of follow-up indicated that compared with HIFU combined with LNG-IUS, HIFU combined with LNG-IUS and a GnRH-a was more effective than HIFU alone or HIFU combined with a GnRH-a [12]. HIFU can significantly relieve patients’ symptoms, reduce lesion volume and improve quality of life; has good cost effectiveness; and accurately ablates adenomyotic lesions without destroying the normal myometrium and endometrium; thus, HIFU is an effective alternative for patients who desire fertility and who refuse surgical treatment [13].

Depending on the type of adenomyosis, the overall pregnancy rate following HIFU treatment ranges from 16.7% to 38.8% [6]. However, a previous study revealed that after HIFU treatment, the pregnancy rates among patients with adenomyosis types I, II, III and IV were 59.6%, 22.9%, 17.6% and 32.0%, respectively, and that there was no significant difference among the four groups in terms of the pregnancy interval, abortion rate, vaginal delivery rate, caesarean section rate or incidence of childbirth complications. In addition, no uterine rupture occurred during pregnancy or delivery [10]. However, there are also case reports suggesting uterine rupture after HIFU treatment, including one case of HIFU treatment for adenomyosis in the first 8 months of unplanned pregnancy and an emergency caesarean section at 38 weeks and 2 days of pregnancy [14]. Another 41-year-old patient conceived via IVF 13 months after HIFU ablation for uterine fibroids and adenomyosis but required emergency caesarean delivery at 37 weeks gestation owing to uterine rupture [15]. With respect to the interval from HIFU treatment to pregnancy, an article on adenomyopathy reported that the median gestation time from HIFU to pregnancy is 10 months after treatment (range 1–31 months) [16]. Another study included 167 patients with six successful pregnancies after HIFU treatment (three with fibroids and three with adenomyosis), with a median pregnancy duration of 5 months after treatment (range 3–15 months) [17]. A study of 100 pregnancies among 231 patients after HIFU treatment revealed that the median time from HIFU to conception was 11 months, no uterine rupture occurred during pregnancy or delivery, IVF–ET following GnRH-a administration resulted in higher pregnancy rates and the long-term cumulative pregnancy rate was significantly greater in the IVF–ET group than in the natural conception group [18]. Currently, no consensus exists on the optimal duration of contraceptive use. In this study, patients adhered to 6 months of contraceptive use, with no significant clinical changes observed during pregnancy follow-up.

Multiple factors may affect the efficacy of HIFU treatment, including the characteristics of adenomyotic lesions, volume and location of adenomyotic lesions, number of hyperintense lesions on T2-weighted imaging (T2WI), uterine position, abdominal wall thickness and distance from the skin surface to the adenomyotic lesions [19]. These factors may also influence treatment strategies and the duration of contraceptive use in patients with adenomyosis. Factors such as a shorter skin-to-lesion distance, internal or focal adenomyosis, reduced vascularity and fewer T2-hyperintense foci on MRI can predict favorable HIFU treatment outcomes [6]. Considering the potential effects of HIFU treatment on tissue structure and physiological function, women of childbearing age who undergo HIFU treatment and subsequently plan to conceive should rigorously adhere to the prenatal examination protocol and undergo regular, standardized obstetric evaluations. Throughout pregnancy, close monitoring for symptoms such as abdominal pain and abnormal bleeding is essential to promptly identify and manage any potential complications, thereby ensuring maternal and fetal safety.

Conclusion

HIFU represents a promising noninvasive therapeutic alternative for adenomyosis through thermal ablation effects, particularly in fertility-preserving contexts. However, the current evidence was derived solely from retrospective case series and is potentially limited by small cohort sizes and selection bias. Future research should prioritize large-scale multicenter randomized controlled trials (RCTs) evaluating efficacy, safety profiles, cost-effectiveness, reproductive outcomes and longitudinal follow-up data to establish the clinical feasibility of HIFU. This evidence will optimize patient selection and treatment sequencing in adenomyosis management to achieve optimal clinical outcomes.

Abbreviations

ART

Assisted reproductive technology

HIFU

High-intensity focused ultrasound

PCS

Pelvic congestion syndrome

PGT

Preimplantation genetic testing

EMT

Endometriosis

LNG-IUS

Levonorgestrel intrauterine release system

RCTs

Randomized controlled trials

IVF–ET

In vitro fertilization–embryo transfer

IVF

In vitro fertilization

IVF/ICSI

In vitro fertilization/intracytoplasmic sperm injection

Author contributions

QYW, YPM, JC, YO and CLY made contributions to the first draft’s conception, design, investigation, analysis and writing. QYW and CLY took part in the supervision, analysis and editing of the data, as well as data curation. All authors have read and agreed to the published version of the manuscript.

Funding

No funding was received for this article.

Data availability

All datasets generated for this study are included in the manuscript.

Declarations

Ethics approval and consent to participate

The studies involving humans were approved by the Ethics Committee of Liuzhou Maternal and Child Health Hospital.

Consent for publication

Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.

Competing interests

The authors declare that they have no competing interests.