Pregnancy-Associated Events in Prognosis and Outcome of Lymphangioleiomyomatosis: A Single-Center Retrospective Analysis

doi:10.21203/rs.3.rs-3791314/v1

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Pregnancy-Associated Events in Prognosis and Outcome of Lymphangioleiomyomatosis: A Single-Center Retrospective Analysis

https://doi.org/10.21203/rs.3.rs-3791314/v1

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Background:

Lymphangiomyomatosis (LAM) is an uncommon condition that primarily impacts women in their reproductive years. Current guidelines discourage pregnancy behavior in women with LAM because to the belief that it raises the risk and does not result in favorable pregnancy outcomes. Pregnancy events have been linked to a higher likelihood of developing pneumothorax and chylothorax, as well as an acceleration in the deterioration of lung function. Currently, there is a deficiency of extensive clinical trials investigating the impact of pregnancy on LAM.

Methods:

The study conducted an integrative analysis by collecting data from the LAM patient registry at the First Hospital of Guangzhou Medical University in Guangzhou, China, as well as from LAM patient organizations in South China. Additionally, the study searched the MEDLINE, Scopus, Embase, and Cochrane Central databases for six relevant clinical articles using the keywords "lymphangiomatosis" and "pregnancy". Retrieve scholarly publications for systematic assessment.

Results:

The study had a total of 133 patients diagnosed with lymphangiomatosis. Out of the total number of patients, 91 individuals (68.4%) experienced irregularities in their menstrual cycles. A single patient was identified with lymphangioleiomyomatosis (LAM) after experiencing pneumothorax during pregnancy. Out of the 12 instances of pregnancy, LAM was identified before conception.One case of dyspnea, one case of renal abnormalities, and one case of tubal pregnancy were identified. Abnormal pregnancy events had place in 25 out of the 173 pregnancies (14.5%) that happened before the diagnosis of LAM. The analysis included six more studies, which reported an incidence of 13.47% for pneumothorax during pregnancy with LAM, 8.30% for dyspnea, and 3.32% for other respiratory abnormalities. Among the five studies that documented aberrant pregnancies, a total of 73 miscarriages (14%), 83 abortions (16%), and 12 other pregnancy outcomes (2%) were reported.

Conclusions:

The elevated incidence of monthly irregularities in individuals with lymphangiomatosis may be attributed to the use of sirolimus and the variable levels of estrogen in patients with lymphangiomatosis. Pregnancy significantly increases the likelihood of experiencing a sudden worsening of lymphangiomatosis-associated pulmonary disease (LAM). Pregnancy might cause a sudden worsening of LAM. LAM exhibits a substantial prevalence of unfavorable reactions during pregnancy, resulting in unfavorable pregnancy results. Consequently, it is advised against getting pregnant in individuals with LAM.

Lymphangiomyomatosis

Pregnancy events

Dyspnea

Pneumothorax

Lymphangioleiomyomatosis (LAM) is a rare neoplastic disease that primarily affects women of reproductive age. It progresses slowly but steadily over time. Within a research investigation comprising 230 participants[1], The study included exclusively female participants, whose ages ranged from 18 to 76 years (mean ± SE, 44.5 ± 0.65 years). The mean age at the commencement of symptoms was 38.9 ± 0.73 years, and at the moment of diagnosis, it was 41.0 ± 0.65 years. Lymphangioleiomyomatosis (LAM) presents itself in two distinct forms: spontaneous (S-LAM) and tuberous sclerosis complex-related (TSC-LAM). Tuberous sclerosis complex (TSC) is an autosomal dominant inherited multisystem neoplastic illness. A significant occurrence of LAM can be identified in adult female patients with TSC[2]. A international prevalence survey conducted in seven countries found that the median prevalence of LAM was 4.9 cases per million female population, with a range of 3.35 to 7.76[3]. Lymphangioleiomyomatosis (LAM) predominantly impacts the respiratory system, lymphatic system, and kidneys. An inherent trait of LAM is the atypical multiplication of smooth muscle cells. From a clinical perspective, the condition is characterized by exertional dyspnea and pneumothorax. Lymphatic blockage can occur as a result of the enlargement of lymph nodes in the abdominal and pelvic regions. LAM is linked to the development of renal angiomyolipomas[4].

Given that a substantial number of Lymphangioleiomyomatosis (LAM) patients are women in their reproductive years, ensuring the safety of pregnancy becomes a prominent issue. According to the European Respiratory Society (ERS) LAM guidelines[5], pregnancy in LAM patients is likely associated with an increased risk of pneumothorax, chylothorax, hemorrhage from vascular smooth muscle tumors, and accelerated decline in lung function. Individualized decisions about pregnancy are advised for LAM patients, with a discouragement of pregnancy in severe situations. This study examined pregnancies occurring both prior to and subsequent to the diagnosis of LAM, with a specific emphasis on unfavorable reactions and outcomes linked to pregnancies following the diagnosis of LAM.

2.1Study Population

The study comprised individuals from the Lymphangioleiomyomatosis (LAM) patient registry at the First Affiliated Hospital of Guangzhou Medical University in China, in addition to LAM patient organizations in the South China region. In September 2021, we disseminated pertinent questionnaires regarding pregnancy occurrences and Lactational Amenorrhea Method (LAM) to the registry and patient groups. Afterwards, offline and telephone follow-ups were carried out with certain patients to verify the accuracy of the gathered data. The retrospective investigation encompassed the examination of LAM subtypes, occurrences of pregnancy and adverse responses, utilization of sirolimus, and genetic factors. The diagnosis of current cases followed the recommendations given by the American Thoracic Society (ATS) and the Japanese Respiratory Society (JRS) in 2017[6]. The research protocol has obtained permission from the Ethics Committee of the First Affiliated Hospital of Guangzhou Medical University.

2.2 Methods

The patients were gathered from the LAM patient Registry at the First Affiliated Hospital of Guangzhou Medical University in China, as well as from LAM patient friends organizations throughout South China. This encompasses patients who experienced a pregnancy event prior to being diagnosed with LAM, patients who were diagnosed with LAM while being pregnant, and patients who had a pregnancy event subsequent to being diagnosed with LAM. Data is gathered with explicit consent using various methods such as online/offline follow-up, telephone follow-up, online surveys, and other means. The MEDLINE, Scopus, Embase, and Cochrane Central databases were searched using the keywords "Lymphangioleiomyomatosis" and "Pregnancy" to find relevant clinical research material. The process of selecting relevant material was conducted autonomously by two assessors based on predetermined inclusion and exclusion criteria. Following the exclusion of clearly irrelevant material, the literature was assessed for its methodological rigor and the findings were verified through cross-checking. If there is a disagreement, it is advisable to invite a neutral third party to facilitate a debate and assessment. The data extraction process encompassed the identification of the primary author of the study, the country of origin, the year of publication, the total number of cases covered, and the principal findings. A total of 90 pertinent literatures were initially obtained, out of which 89 were excluded due to duplication. Subsequently, 71 literatures were assessed based on their titles and abstracts. After conducting a thorough assessment of the literature and excluding studies with insufficient sample sizes and inaccurate data statistics, a total of six relevant literatures were considered.

The following information was collected: (1) LAM-related symptoms of female LAM patients of childbearing age before, during and after pregnancy. The pertinent data prior to pregnancy were defined as the most recent follow-up report between the diagnosis of LAM and the occurrence of pregnancy. Postpartum data refers to the initial follow-up report following the conclusion of the pregnancy event. (2) Document the patient's symptoms prior to and following pregnancy, and ascertain if there is a worsening of symptoms based on the patient's subjective perception. (3) The administration of sirolimus prior to and following the occurrence of pregnancy was documented. (4) The results of pregnancies and any anomalies during pregnancy were documented. (5) Initially, 90 pertinent literatures were obtained for further evaluation. After excluding studies with inadequate sample size and inaccurate statistical data, a total of six literature sources were selected.

3.1Patient Characteristics and Pregnancy Outcomes

We collected 138 valid questionnaires, and after applying inclusion and exclusion criteria, 133 confirmed Lymphangioleiomyomatosis (LAM) patients were included in the study (Fig. 1). Of these, 103 had documented pregnancy histories, while 30 did not. Ninety-two cases experienced pregnancies before the diagnosis of LAM, one received a diagnosis of LAM during pregnancy, and eight had pregnancies after the LAM diagnosis. Among the 133 diagnosed patients, 17 had Tuberous Sclerosis Complex-related LAM (TSC-LAM), and 116 had Sporadic LAM (S-LAM). Menstrual abnormalities were prevalent in 91 cases (68.4%), with concurrent renal angiomyolipoma in 37 cases (27.8%) and uterine fibroids in 29 cases (21.8%) (Table 1). There were 92 cases of pregnancies before LAM diagnosis, resulting in 173 pregnancy events. Of these, 20 cases (21.7%) were abnormal pregnancies, and 25 cases (14.5%) had abnormal pregnancy events, with symptoms including respiratory distress in 10 cases and pneumothorax in 3 cases (Table 2). Eight cases were diagnosed with LAM after pregnancy, resulting in 12 pregnancy events. Among these, 9 were normal pregnancies, and 3 were abnormal pregnancies, including respiratory distress, the discovery of renal angiomyolipoma, and tubal pregnancy. Two cases had abnormal pregnancies, with one resulting in a miscarriage. One case was diagnosed with LAM during pregnancy, presenting with pneumothorax. Ninety-two cases were diagnosed with LAM before pregnancy, resulting in 173 pregnancy events. There were 12 cases (6.9%) of abnormal pregnancy events, and 50 cases (28.9%) ended in miscarriage as the pregnancy outcome.

Table 1

Menstrual status and concurrent symptoms of LAM patients
				Number of people/Value (percentage)
Patient				133
Gender
	Females			133
Age (years)				40.4 ± 9
Diagnosis
	Diagnosed LAM			133
			TSC-LAM	17
			S-LAM	116
Menstruation
	Normal			42(31.6%)
	Abnormal			91(68.4%)
		Before taking sirolimus		60
			Early menstruation	14
			Delayed menstruation	26
			Decreased menstrual flow	22
			Increased menstrual flow	5
			Other	4
		After taking sirolimus		31
			Early menstruation	3
			Delayed menstruation	12
			Decreased menstrual flow	8
			Increased menstrual flow	7
			Other	11
Complications
	Without complications			41(31.58%)
	Without complications			92(68.42%)
		hamartoma of kidney		37
		myoma of uterus		29
		hypertension		16
		diabetes		5
		thyroid disease		4
		polycystic kidney		3
		breast cancer		2
		other		6

Table 2

Pregnancy records and birth outcomes of LAM patients
			Number of patients (percentage)	Frequency (percentage)
Total			133
No pregnancy			30
Pregnancy			103	188
Diagnosis before pregnancy			8	12
	Normal Pregnancy		5(62.5%)	9(75%)
	Abnormal Pregnancy		3(37.5%)	3(25%)
Abnormal symptom
		Dyspnea	1(12.5%)	1(8.3%)
		Pneumothorax	0(0%)	0(0%)
		Chylothorax	0(0%)	0(0%)
		Other	2(25%)	2(16.7%)
Parturition
	Normal parturition		7(87.5%)	9(75.0%)
	Abnormal parturition		1(12.5%)	2(16.7%)
	Abortion		1(12.5%)	1(8.3%)
Diagnosis during pregnancy			1	1
(Normal parturition)
Diagnosis after pregnancy			92	173
	Normal Pregnancy		72(78.3%)	148(85.5%)
	Abnormal Pregnancy		20(21.7%)	25(14.5%)
Abnormal symptom
		Dyspnea	9(12.5%)	10(5.8%)
		Pneumothorax	3(3.3%)	3(1.7%)
		Chylothorax	1(1%)	1(0.6%)
		Other	14(15.2%)	19(11%)
Parturition
	Normal parturition		50(54.3%)	111(64.2%)
	Abnormal parturition		9(9.8%)	12(6.9%)
	Abortion		33(35.9%)	50(28.9%)

3.2 Menstrual Abnormalities in LAM and the Use of Sirolimus

The current study reaffirms the correlation between the frequent occurrence of monthly irregularities in patients with lymphangioma (LAM) and the administration of sirolimus, as well as the variable levels of estrogen in LAM patients[7]. Among the 133 LAM patients included in this study, 42 cases (31.6%) had normal menstruation and 91 cases (68.4%) had abnormal menstruation, including early menstruation, delayed menstruation and reduced menstrual volume. In addition, 31 patients reported significant menstrual disorders after taking sirolimus, and a few patients improved or even disappeared after taking reduced amounts of sirolimus. Sirolimus, as a first-line drug for the treatment of LAM, inhibits the proliferation of LAM cells as an mTOR inhibitor, which may cause metabolic diseases, hemodynamic diseases, and hematological system diseases, but there is little evidence for menstrual disorders. In a study [8], among 74 patients, seven cases exhibited menstrual disturbances attributable to mTOR inhibitor treatment. The symptoms include amenorrhea, menorrhagia, and uterine hemorrhage, which spontaneously resolve or cease upon discontinuation of medication. Given the intimate connection between LAM and estrogen, it is uncertain if aberrant menstruation in LAM patients is directly linked. However, we have observed that sirolimus can temporarily impact the menstrual cycle, even with a brief intervention. Nevertheless, it is recommended for individuals with LAM to undertake blood tests and gynecological examinations while administering Sirolimus. Additionally, close monitoring is essential to assist patients in effectively managing any potential menstrual abnormalities.

3.3Complications of LAM and Adverse Reactions During Pregnancy

In the present investigation, it was found that the natural course of LAM is also complicated by diabetes mellitus, hypertension, renal malformation tumour, breast cancer, uterine leiomyoma, thyroid disease, polycystic kidney and other diseases (Fig. 2). Among them, renal malformations and uterine fibroids are the most obvious, due to the similarity of the pathogenesis of renal malformations and LAM[9], pulmonary lymphangioleiomyomas may originate from the uterus [10], and 56 (42%) of the 133 patients in this study have a history of renal malformations or uterine fibroids in combination, among which 8 cases of LAM have a history of renal malformations and uterine fibroids at the same time (Fig. 3), so that renal malformations or uterine fibroid patients, especially women of childbearing age, should be aware of their normal lung function to exclude the possibility of LAM.

Among the 133 patients with LAM included in this study, there were 188 pregnancy events and 28 (14.9%) pregnancy events with adverse reactions, which included dyspnoea, pneumothorax, and celiac disease. The likelihood of negative responses during pregnancy following the identification of LAM was higher (Fig. 4), and at the same time, during the investigation, it was discovered that certain patients experienced their initial adverse reactions, such as pneumothorax and dyspnea, during pregnancy prior to being diagnosed with LAM. These patients were subsequently diagnosed with LAM within 1–2 years after giving birth. Therefore, it is plausible that pregnancy events may have expedited the progression of the disease in LAM patients. In the remaining six studies analyzed, similar findings were seen. The probability of experiencing symptomatic episodes, such as pneumothorax and dyspnea, was higher. Additionally, pneumothorax was frequently the initial symptom in cases of pregnancy following the diagnosis of LAM. The incidence of pneumothorax was 13.47%, dyspnoea 8.30% and other respiratory abnormalities 3.32% (Table 3). Patients with LAM are currently considered to be at greater risk for pregnancy and a thorough pulmonary function assessment should be performed when considering pregnancy.

Table 3

Adverse reactions and complications during pregnancy in patients with LAM
	Nation	Caseload	The number of pregnancies recorded	Number of pregnancy events	Pneumothorax			Dyspnea			Other respiratory diseases
	Nation	Caseload	The number of pregnancies recorded	Number of pregnancy events	Dbp	Ddp	Dap	Dbp	Ddp	Dap	Dbp	Ddp	Dap
Cohen MM[15]	England	328	204	365	4	10	18	1	10	25	4	1	9
Hyslop A[16]	America	50	38	80	21Δ			*Δ			*Δ
Shen L[17]	China	48	48	66	3	*	2	7	*	*	0	*	*
Taveira-DaSilva AM [18]	Japan	16	16	16	5	*	*	2	*	*	0	*	*
Johnson SR[19]	The United Kingdom	50	7	7	3	*	*	0	*	*	chylothorax (n = 2)	*	*
Seyama K ^[11^]	The United States	8	8	8	7	*	*	0	*	*	0	*	*
Total		500	321	542	73(13.47%)			45(8.30%)			18(3.32%)

Sig Dbp: Diagnosis before pregnancy; Ddp༚Diagnosis during pregnancy༛ Dap༚Diagnosis after pregnancy.“*” indicates that this data was not mentioned in the cited study. “Δ”indicates that no specific classifications were made in this study

3.4 Pregnancy outcomes in LAM

Of the 188 pregnancy events in this study, 121 were normal deliveries, 14 were abnormal deliveries, and 51 were miscarriages. The atypical pregnancy conditions encompassed ectopic pregnancy, fetal abnormalities, and fetal malposition. The majority of the miscarriages were deliberately caused, although a small number occurred naturally as spontaneous abortions or due to the halt in fetal growth. The majority of the abortions were deliberate, with a small number being natural miscarriages and fetal growth halt. The causes for induced abortions included respiratory distress during pregnancy, a decrease in lung function that made it impossible to continue the pregnancy, and the decision to terminate the pregnancy owing to concerns about a genetic susceptibility to LAM. The incidence of abnormal births is greater in pregnancies following LAM diagnosis compared to pregnancies preceding LAM diagnosis (Table 4), so it is crucial for patients with LAM to get regular mid-pregnancy examinations in order to thoroughly evaluate the condition of the developing fetus. Additionally, they should carefully contemplate induced abortions in cases of ectopic pregnancies and other problematic pregnancy situations. In the other five studies included in this study, there were 534 pregnancy events, 366 normal pregnancies (69%), 73 abnormal pregnancies (14%), 83 miscarriages (16%), and 12 other pregnancy outcomes (2%). Ultimately, the outcomes of pregnancy in patients with LAM are unfavorable, characterized by elevated rates of miscarriage and a significant likelihood of abnormal pregnancies. Consequently, it is not advisable for people with LAM to pursue pregnancy.

Table 4

Pregnancy outcomes in patients with LAM
	Nation	Caseload	The number of pregnancies recorded	Number of pregnancy events	Normal pregnancy			Abnormal pregnancy			Abortion			Others
	Nation	Caseload	The number of pregnancies recorded	Number of pregnancy events	Dbp	Ddp	Dap	Dbp	Ddp	Dap	Dbp	Ddp	Dap	Dbp	Ddp	Dap
Cohen MM[12]	England	328	204	365	9	5	254	5	9	44	1	1	30	0	0	7
Hyslop A[13]	America	50	38	80	52Δ(65%)			9Δ(11%)			14Δ(18%)			5Δ(6%)
Shen L[14]	China	48	48	66	10	*	20	*	*	*	24	*	12	0	*	0
Taveira-DaSilva AM [15]	Japan	16	16	16	15	*	*	1	*	*	0	*	*	0	*	*
Johnson SR[16]	The United Kingdom	50	7	7	1	*	*	5	*	*	1	*	*	0	*	*
Total		492	313	534	366(69%)			73(14%)			83(16%)			12(2%)
Sig Dbp: Diagnosis before pregnancy; Ddp༚Diagnosis during pregnancy༛ Dap༚Diagnosis after pregnancy. “*” indicates that this data was not mentioned in the cited study. Abortion events include induced abortion and spontaneous abortion. “Δ”indicates that no specific classifications were made in this study

The main findings of our analyses were (1) Sirolimus treatment of LAM may cause menstrual disorders, which mostly reduce or disappear after dose reduction or discontinuation of the drug. (2) Pregnancy events can expedite the progression of LAM. (3) Pregnancies affected with LAM are more susceptible to unfavorable pregnancy outcomes, characterized by a significant occurrence of adverse events. Clinicians are advised to modify treatment plans based on LAM follow-up and to conduct thorough evaluation of lung function prior to pregnancy.

At the molecular level, the activation of ERK1/2 is crucial for promoting endothelial cell proliferation, migration, and survival. Within cells lacking TSC2, the activation of ERK1/2 results in the phosphorylation of PKM2 at Ser37. This phosphorylation event impacts the transcription of HIF-1α, resulting to cell proliferation. Furthermore, the phosphorylation of PKM2 is dependent on estrogen, highlighting the significant role of estrogen in activating the ERK pathway[17].Oestrogen has an inhibitory influence on the development of LAM. During pregnancy, oestrogen levels rise, reaching their maximum relative ratio to progesterone during mid-pregnancy[18]. These factors may have caused negative outcomes such as pneumothorax and difficulty breathing in individuals with LAM during pregnancy, and events that increased estrogen levels may have sped up the progression of LAM. Simultaneously, 17β-estradiol exerts its effects via estrogen receptors α and β, and it plays a crucial role in maintaining the balance of tubal cells and controlling the normal physiological activities of the fallopian tubes.Variations in E2 levels can result in fallopian tube malfunction and elevate the likelihood of ectopic pregnancy[19], and the same high percentage of tubal pregnancy LAM was present in our survey. To summarize, fluctuations in oestrogen levels have an impact on the progression of LAM, pregnancy, and lung function. Therefore, the therapy of LAM should aim to preserve a balanced oestrogen level. Based on the investigation, it was found that some patients experienced abnormal menstruation when taking sirolimus, which is the primary medication for treating LAM. This suggests that their estrogen levels are not following the normal pattern. Clinicians should adjust the dosage of sirolimus accordingly to maintain a normal level of estrogen and progesterone, as this may lead to greater benefits for LAM patients. Currently, the prognosis for LAM pregnancies is unfavorable, characterized by a significant likelihood of aberrant pregnancy occurrences and a high prevalence of respiratory complications, including pneumothorax, dyspnea, and celiac disease. The likelihood of abortion in LAM is elevated, primarily as a result of apprehension regarding the potential exacerbation of the LAM illness during pregnancy, the concern of transmitting the disease to the offspring, or, in certain instances, the decision to terminate the pregnancy based on the recommendation of a healthcare practitioner. We posit that pregnant events have a role in the rapid advancement or hastening of the natural progression of LAM, whereas the impact of pregnancy-related hemodynamic and cardiorespiratory burdens cannot be disregarded. Consequently, it is advised against getting pregnant for individuals with LAM. However, for those who strongly desire to conceive, it is crucial to evaluate estrogen levels, as well as pulmonary and tubal function, before attempting pregnancy. Additionally, it is recommended to conduct more frequent pregnancy tests during pregnancy and terminate the pregnancy if a severe adverse event occurs.

The study collected questionnaires from various sources, including online and offline channels. A total of 738 questionnaires were distributed through the LAM patient registry of the First Affiliated Hospital of Guangzhou Medical University in China and the LAM patient organizations in South China. Out of these, only 138 questionnaires were returned, indicating a significant rate of non-response to the online questionnaires. The low patients' trust in online questionnaires may be attributed to the fact that the questionnaire primarily focuses on sensitive topics such as pregnancy, labor, delivery, and other private matters. Despite being released by the group owner and licensed physicians with relevant online certifications, the aforementioned issues persist. To maintain the credibility of this study, questionnaires with insufficient information and from unidentified sources underwent rigorous screening, leading to a low proportion of legitimate surveys in this study.

Availability of data and materials

The dataset used in this research and analysis were available from the corresponding authors.

Acknowledgements

The authors thank all LAM patients who participated in this study.

Funding

This work was supported by the 2023 Natural Science Foundation of Guangdong Province Project (2023A1515010308), the Guangdong Provincial Natural Science Foundation Top Project (2021A1515011352), the Key Project of Independent Subject Funding of Guangzhou Institute of Respiratory Health (ZNSA-2020013), the Project of Guangzhou Medical University's 2022 Annual Student Innovation Ability Enhancement Plan (02-408-2203-2106), the National Key Research and Development Programme: Key Special Project for Precision Medicine Research (2016YFC0901502), and the Guangdong Provincial Research Fund for Medical Science and Technology Project (A2015018).

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Authors and Affiliations

The First Affiliated Hospital of Guangzhou Medical University (Department of Respiratory and Critical Care Medicine), National Respiratory Medicine Centre, Guangzhou Respiratory Health Research Institute, State Key Laboratory of Respiratory Diseases, National Clinical Medical Research Centre for Respiratory Diseases, Guangzhou 510120, China

Jingye Tai , Shihua Liu , Xinping Yan , Zixin Fan ,Yingxin Pan , Hongyuan Huang , Zhen Zhao , Beini Xu , Weilin Wang ,Jie Liu

Department of Respiratory Disease, The First Affiliated Hospital, Guangzhou Medical University, Guangzhou, China

Jie Liu

Contributions

JYT,JL: design, data collection, analysis, and manuscript writing.SHL,XPY,LTH,ZXF: data collection and analysis.YXP,HYH,ZZ,BNX,WLW : data collection. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Jie Liu

Ethics declarations

Ethical approval and consents to participate

The protocol of this retrospective analysis was approved by the Ethics Committee of the First Affiliated Hospital of Guangzhou Medical University (ES-2023-226). All patients provided written informed consent.

Consent for publication

Consent for publications were obtained from all participants.

Competing interests

The authors declare no potential conflicts of interest with respect to the research, authorship, and publication of this article.

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Pregnancy-Associated Events in Prognosis and Outcome of Lymphangioleiomyomatosis: A Single-Center Retrospective Analysis

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Abstract

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Background

Methods

2.1Study Population

2.2 Methods

Results

3.1Patient Characteristics and Pregnancy Outcomes

3.2 Menstrual Abnormalities in LAM and the Use of Sirolimus

3.3Complications of LAM and Adverse Reactions During Pregnancy

3.4 Pregnancy outcomes in LAM

Discussion

Declarations

References

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