Recent Advances in Vaginal Atresia: A Literature Review

Abstract

Vaginal atresia is a rare anomaly of the female reproductive tract that significantly impacts women’s reproductive health and quality of life. Although there has been relatively extensive research on the clinical manifestations and differential diagnosis of vaginal atresia, there is a paucity of literature specifically addressing the genetic background, treatment protocols, and psychological status of patients with vaginal atresia, indicating a need for further investigation. In this context, this article systematically reviews the epidemiological characteristics of vaginal atresia and explores its etiology from multiple perspectives, including developmental processes, genetic factors, and environmental factors, emphasizing the importance of genetic susceptibility and environmental interactions in the pathogenesis of the condition. Building upon a summary of the clinical presentations, classification, and diagnostic methods of vaginal atresia, this article provides an overview of current treatment strategies for both partial vaginal atresia and complete vaginal atresia, discusses the psychological status of affected patients, and examines fertility outcomes and sexual function. The aim is to offer insights and recommendations for future research on vaginal atresia, ultimately striving to enhance the quality of life for affected individuals.

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Academic Editors: Nikolaos
Machairiotis and Carlo Bulletti
Received: 17 November 2024
Revised: 19 December 2024
Accepted: 7 January 2025
Published: 8 January 2025
Citation: Lin, X.; Kang, J.; Zhu, L.
Recent Advances in Vaginal Atresia:
A Literature Review. Biomedicines
2025,13, 128. https://doi.org/
10.3390/biomedicines13010128
Copyright: © 2025 by the authors.
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This article is an open access article
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Review
Recent Advances in Vaginal Atresia: A Literature Review
Xijuan Lin, Jia Kang * and Lan Zhu *
Department of Obstetrics and Gynecology, National Clinical Research Center for Obstetric and Gynecologic
Diseases, Peking Union Medical College Hospital, State Key Laboratory for Complex Severe and Rare Diseases,
Peking Union Medical College, Chinese Academy of Medical Sciences, No. 1 Shuaifuyuan, Beijing 100005, China;
xijuanlin@foxmail.com
*Correspondence: kangjiasdu@163.com (J.K.); zhu_julie@vip.sina.com (L.Z.)
Abstract: Vaginal atresia is a rare anomaly of the female reproductive tract that significantly
impacts women’s reproductive health and quality of life. Although there has been relatively
extensive research on the clinical manifestations and differential diagnosis of vaginal atresia,
there is a paucity of literature specifically addressing the genetic background, treatment
protocols, and psychological status of patients with vaginal atresia, indicating a need for
further investigation. In this context, this article systematically reviews the epidemiological
characteristics of vaginal atresia and explores its etiology from multiple perspectives, in-
cluding developmental processes, genetic factors, and environmental factors, emphasizing
the importance of genetic susceptibility and environmental interactions in the pathogenesis
of the condition. Building upon a summary of the clinical presentations, classification,
and diagnostic methods of vaginal atresia, this article provides an overview of current
treatment strategies for both partial vaginal atresia and complete vaginal atresia, discusses
the psychological status of affected patients, and examines fertility outcomes and sexual
function. The aim is to offer insights and recommendations for future research on vaginal
atresia, ultimately striving to enhance the quality of life for affected individuals.
Keywords: vaginal atresia; research advances; genetic factors; treatment strategies; fertility
outcomes
1. Background
Vaginal atresia is a rare anomaly of the female reproductive tract caused by abnormal
development of the urogenital sinus and Müllerian ducts, leading to an incomplete vaginal
canalization [
1
]; the incidence of vaginal atresia is estimated to be approximately 1 case
per 10,000 to 15,000 female newborns [
2
]. Patients typically present with normal external
genitalia, and a normal uterus, fallopian tubes, and ovaries, while experiencing partial or
complete vaginal atresia. According to the updated classification system from the European
Society of Human Reproduction and Embryology (ESHRE) and the European Society for
Gynaecological Endoscopy (ESGE), for female reproductive tract anomalies, vaginal atresia
is categorized as U0–4/C0–3/V4 [
3
]. A study involving 67 patients with vaginal atresia
found that 25 patients (37.3%) had associated lower vaginal atresia, 36 patients (53.7%)
had complete vaginal atresia, 1 patient (1.5%) had upper vaginal atresia, and 5 patients
(7.5%) had vaginal apex atresia [
4
]. To facilitate clinical diagnosis and communication,
the Obstetrics and Gynecology Branch of the Chinese Medical Association further clas-
sifies vaginal atresia into distal vaginal atresia and complete vaginal atresia. The former
features a normally developed upper vaginal segment, cervix, and uterine body, with func-
tional endometrium, while the latter often involves cervical developmental abnormalities,
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Biomedicines 2025,13, 128 2 of 14
with a normally developed uterine body or a malformed uterine body with a functional
endometrium [5].
Globally, vaginal atresia is often not diagnosed until puberty, with patients typically
presenting due to primary amenorrhea or cyclical lower abdominal pain. Reports indicate
that in the United States, vaginal atresia is the second most common cause of primary
amenorrhea in tertiary care centers [
6
,
7
]. Furthermore, due to the complexity of its diagnosis,
the actual incidence may be underestimated. Most cases of vaginal atresia are identified
during puberty due to the absence of menstruation or difficulties with sexual intercourse,
particularly in developing countries, where a lack of relevant knowledge often leads to
delayed diagnosis. In China, the median age at diagnosis of vaginal atresia is approximately
12 years [8].
2. Etiology: Developmental Processes, Genetic Factors, and
Environmental Influences
The embryonic origin of the vagina remains unclear, with four main hypotheses
proposed. The most widely accepted theory suggests the upper two-thirds of the vagina
develops from the Müllerian ducts, while the lower one-third arises from the urogenital
sinus [
9
]. This hypothesis suggests that the upper two-thirds of the vagina develop from
the Müllerian ducts, while the lower one-third arises from the growth and canalization of
the urogenital sinus epithelium. The second hypothesis posits that the vagina originates
entirely from the Müllerian ducts, with both the vaginal bulb and vaginal plate derived
from this structure [
10
,
11
]. The third hypothesis combines the Müllerian and Wolffian
duct origins, suggesting that the vagina develops from both the Müllerian and Wolffian
ducts [
12
,
13
]. Finally, the “urogenital sinus origin” model asserts that the squamous
epithelium of the cervix and vagina arises from the urogenital sinus, proposing that the
squamous epithelium grows upward, replacing the columnar epithelium of the Müllerian
ducts. All of these theories are based on anatomical and histological observations, with
no definitive evidence confirming the embryonic origin of the vaginal epithelium. Recent
lineage-tracing studies in mice support this “Müllerian duct + urogenital sinus” hypothesis,
showing that the vaginal epithelium entirely originates from the Müllerian duct, with no
contribution from the Wolffian duct [14].
Additionally, disorders of sexual development, such as androgen insensitivity syn-
drome (AIS) in XY individuals and congenital adrenal hyperplasia (CAH) in XX individuals,
provide valuable insights into the processes of vaginal development. In individuals with
complete AIS, despite having an XY chromosomal pattern, female external genitalia and
a blind-ending vagina may develop, but the proximal vagina, cervix, and uterus are ab-
sent [
15
]. In contrast, XX females with CAH, who are exposed to excess androgens, retain
a female-structured upper vagina and uterus, but exhibit abnormal external genitalia,
ranging from a mildly enlarged clitoris, reduced vaginal opening with a separate urethral
opening, and posterior labial fusion, to complete male virilization with a phallus, complete
fusion of the labial folds, a single urethral opening at the glans penis, and a normally
formed but empty scrotum [
16
]. These conditions help to further elucidate the origin of the
vagina, suggesting that its development involves contributions from both the Müllerian
ducts and the urogenital sinus, thereby advancing our understanding of the embryonic
origin of the vagina.
Due to the lack of large pedigrees suitable for linkage analysis, researchers have
employed association studies, functional studies, gene expression analysis, animal experi-
ments, and bioinformatics research to screen for relevant genes and assess their pathogenic-
ity in vaginal atresia.

Biomedicines 2025,13, 128 3 of 14
Gene mutations in genes such as TBX6 and the Tyro3 RTK family (including Tyro3,
Axl, and Mer) are linked to distal vaginal atresia. The TBX family of transcription factors
plays important roles in development, and TBX6 has been identified as a potential gene
involved in vaginal development [
17
], though further research is needed. Similarly, in
animal models, mutations in TBX3 and the Tyro3 RTK family have been associated with
vaginal atresia [
18
,
19
]. In particular, Mer appears to be the most crucial gene in this family
for vaginal development, with Axl and Tyro3 possibly supporting its function [
20
]. In
addition, a spontaneous point mutation in the Lhfpl2 gene in mice has been shown to
cause abnormal vaginal septum formation, the underdevelopment of the lower vagina,
and normal ovary and uterus development [
21
]. As well as this, Adamts18 plays a role
in regulating the vaginal opening by affecting the fusion of the Müllerian ducts and the
apoptosis of vaginal cells in mice [22].
Research has also identified chromosomal abnormalities associated with vaginal
atresia. For example, a study found a uniparental disomy on chromosome 2 in some cases of
distal vaginal atresia [
8
], which may affect genes involved in apoptosis, immune response,
and tissue development. Additionally, duplications on chromosome 17q12, including
the genes HNF1B and LHX1, have been linked to vaginal atresia. HNF1B is particularly
important for urogenital development [
23
–
25
]. Insertions on chromosome 21q22.3q23.3
might also contribute [
26
]. These findings suggest that chromosomal abnormalities may
play a role in the development of vaginal atresia, alongside other genetic mutations.
Despite the current progress in understanding the genetic factors associated with
vaginal atresia, and the establishment of animal models to study the condition, the genetic
background of vaginal atresia remains poorly understood. Further research is needed to
continue elucidating the complex genetic mechanisms underlying this congenital anomaly.
Currently, the field of genetic diagnosis for congenital malformations is developing rapidly.
Early diagnosis of congenital defects can significantly improve diagnostic accuracy and
help tailor personalized treatment plans, ultimately improving neonatal outcomes.
Environmental factors may also contribute to vaginal atresia by influencing gene
expression or physiological events during development [
27
]. Maternal health status, nutri-
tional levels, medication use, or exposure to specific environmental toxins during pregnancy
could all impact the development of the fetal reproductive system. For instance, prenatal ex-
posure to steroid medications may interfere with gonadal development, thereby increasing
the risk of vaginal atresia. Due to maternal estrogen stimulation of the uterus and cervical
glands, distal vaginal atresia may manifest during the neonatal period [
28
]. However,
the mechanisms and specific associations of these environmental factors require further
investigation for clarification.
3. Clinical Manifestations
Patients with vaginal atresia have a 46,XX karyotype, with partial or complete un-
derdevelopment of the vagina. The uterus and cervix may be normal or exhibit fusion or
resorption defects, with the distal or entire vagina replaced by fibrous tissue. At puberty,
these patients may present with primary amenorrhea, cyclic pain, and pelvic masses. If
retrograde menstruation is not detected in time, it can lead to endometriosis and pelvic
adhesions [29–32].
In cases of congenital distal vaginal atresia, due to normal endometrial development
and functional endometrium, menstrual blood cannot exit at menarche, resulting in early
hematocolpos formation. This manifests as a large hematoma in the upper vagina, which
can lead to hematocervix, hematometra, and hemoperitoneum in severe cases. On rectal
examination, the mass is typically located low. Symptoms present early with severe
abdominal pain and prominent masses, leading patients to seek medical attention early,

Biomedicines 2025,13, 128 4 of 14
making surgery less complicated and prognosis favorable [
8
]. However, some researchers
note that a portion of distal vaginal atresia patients may exhibit severe manifestations in
the neonatal period, including obstructive uropathy, intestinal obstruction, urinary tract
infections, or systemic sepsis [33].
Congenital total vaginal atresia is often associated with cervical malformations, though
uterine development is generally preserved and functional endometrium is present. Con-
sequently, symptoms appear later, with milder abdominal pain and less obvious masses,
often leading to delayed medical consultation [
34
]. Complete vaginal atresia may result in
hematosalpinx, hemoperitoneum, and pelvic endometriosis. In a cohort study by Karina
et al., 66.7% of patients with distal vaginal underdevelopment had endometriosis, and
100% of patients with cervical and vaginal underdevelopment had endometriosis [31].
Vaginal atresia is frequently associated with other malformations. These may include
other congenital Müllerian duct anomalies, such as a unicornuate uterus and septate uterus,
urogenital anomalies like renal dysplasia and congenital vesicovaginal fistula, and other
congenital malformations such as scoliosis, cardiac anomalies, polydactyly, and anal atresia.
4. Diagnosis and Differential Diagnosis of Vaginal Atresia
The diagnosis of vaginal atresia involves a comprehensive approach, incorporating
clinical manifestations, gynecological examination, imaging, and laparoscopic exploration
to confirm the atresia location, type, and complications. The diagnostic process is crucial,
as early identification and appropriate treatment options directly impact the patient’s
quality of life and fertility potential. Clinical manifestations and gynecological examination
are often the initial diagnostic clues, primarily including primary amenorrhea, cyclic
abdominal pain, pelvic masses, and the absence or closure of the vaginal introitus. However,
detailed diagnosis often requires imaging assistance, such as pelvic ultrasound or magnetic
resonance imaging (MRI) [
2
]. Pelvic ultrasound is relatively accessible and easier to perform,
though it has higher rates of missed or misdiagnosis. MRI’s superior soft-tissue contrast
and multiplanar capabilities make it the gold standard for evaluating complex uterine
malformations [
35
]. Finally, due to the limitations of clinical manifestations, gynecological
examination, and imaging, laparoscopy may be performed when necessary to determine
conditions such as endometriosis.
Conditions commonly confused with vaginal atresia include imperforate hymen and
Mayer–Rokitansky–Küster–Hauser (MRKH) syndrome. Imperforate hymen primarily
results from uncanalized urogenital sinus tissue, with less abdominal pain than in vaginal
atresia patients, and the mass typically located in the vagina rather than the pelvis. Due to
hematocolpos, patients with imperforate hymen may exhibit a bluish-purple hymen [
36
].
MRKH syndrome patients typically present with an absent uterus and vagina, though
some with functional endometrium may exhibit primary amenorrhea and cyclic lower
abdominal pain. Gynecological examination reveals only a shallow vaginal dimple without
hematocolpos [
37
]. Though MRI, ultrasound, and other imaging techniques may confuse
vaginal atresia with these two types of genital anomalies, clinicians should carefully assess
clinical manifestations and gynecological findings to achieve a more precise differential
diagnosis. However, their treatment differs: vaginal atresia primarily requires surgery,
while MRKH syndrome typically involves vaginal dilation first. Differences in uterine
development mean vaginal atresia patients more frequently need obstruction relief. Misdi-
agnoses and unclear distinctions in the literature, particularly between distal and complete
vaginal atresia, can lead to treatment delays and inaccuracies. Scholars are urged to clearly
classify and describe these conditions to improve diagnosis, treatment, and academic com-
munication, ultimately advancing research and clinical practice. Comparisons of vaginal
atresia, MRKH Syndrome, and imperforate hymen are summarized in Table 1.

Biomedicines 2025,13, 128 5 of 14
Table 1. Comparison of vaginal atresia, Mayer-Rokitansky-Küster-Hauser Syndrome (MRKH Syn-
drome), and imperforate hymen.
Distal Vaginal
Atresia
Complete Vaginal
Atresia MRKH Syndrome Imperforate Hymen
Cause
Underdevelopment of
the lower vagina,
leading to an absent
vaginal opening but a
normal external
genital appearance.
Complete vaginal
closure, often
associated with
underdeveloped
cervix and uterus.
Congenital absence of
the vagina and uterus,
often due to
underdevelopment of
the paired
Müllerian ducts.
Failure of the hymen
to perforate, leading
to obstruction at the
vaginal opening.
Clinical
Manifestations
Normal external
genitalia,
no vaginal opening.
Upper vagina may be
dilated with blood
accumulation.
Similar to lower
vaginal atresia but
often associated with
cervical and uterine
malformations.
Primary amenorrhea,
normal external
genitalia, shallow
vaginal dimple (or no
vaginal opening),
absent or
underdeveloped
uterus.
Primary amenorrhea
due to menstrual
blood accumulation,
with cyclic
abdominal pain.
Vaginal Findings
No vaginal opening;
mucosal surface of
the upper vaginal
segment
appears normal.
Complete absence of
the vaginal opening;
may have vaginal
bulging from blood
accumulation.
Shallow vaginal
dimple with no true
vaginal canal.
Imperforate hymen
with no vaginal
opening, bulging
hymen due to blood
accumulation.
Abdominal Pain
Often severe due to
hematocolpos (blood
accumulation),
leading to pelvic pain.
Severe abdominal
pain from blood
reflux and pelvic
masses, including
hematocolpos and
possible
endometriosis.
No menstrual blood
obstruction; cyclical
abdominal pain may
occur only if a
functional
endometrium
is present.
Mild abdominal pain
due to blood
retention in the
uterus and/or
fallopian tubes,
usually less severe
than in
vaginal atresia.
Pelvic Mass
Palpable mass located
anterior to the rectum,
below the
hymenal level.
Larger pelvic masses
in the form of blood
accumulation,
affecting the uterus,
fallopian tubes,
and ovaries.
No significant pelvic
mass, though a small
palpable mass may be
felt if a rudimentary
uterus exists.
Palpable cystic mass
in the vagina due to
accumulated blood,
possibly with
protrusion of
the hymen.
Finally, diagnostic delays in developing countries should also be noted. In these
regions, limited access to healthcare, a lack of awareness among healthcare providers, and
cultural stigmas surrounding reproductive health contribute to delayed diagnosis and
treatment. The shortage of trained medical professionals and inadequate diagnostic tools
often prevent early detection. To address these barriers, just like other disease requiring
early diagnosis, reducing stigmas, increasing public awareness improving training for
healthcare providers, and expanding access to diagnostic services in rural and underserved
areas are crucial steps [
38
]. Increasing financial access in these regions might also be
crucial [39].
5. Treatment of Vaginal Atresia
The first-line treatment for patients with vaginal atresia is surgical intervention to
relieve the obstruction [
40
]. For all types of vaginal atresia, the primary goals of surgery are
to alleviate the obstruction, restore anatomical function, and prevent recurrence. However,

Biomedicines 2025,13, 128 6 of 14
given the varying degrees of uterine and cervical development in patients with different
levels of vaginal atresia, as well as differing fertility requirements, specific treatment
strategies—such as the choice of surgical approach and the material used to cover the
newly created vaginal surface—may differ and often require individualized consideration.
5.1. Surgical Options for Distal Vaginal Atresia
Surgery for distal vaginal atresia has a high success rate and generally involves
opening the atretic segment and draining menstrual blood from the upper vagina. The
treatment for distal vaginal atresia primarily involves surgical incision of the atretic vaginal
segment and relieving the obstruction. Surgery is not strictly required during menstruation,
but if there is hematocolpos, the surgery should be performed as soon as possible to relieve
the obstruction. First, perform a puncture to drain the blood and clarify the direction
before incising the atretic part, and then try to dilate the incision. The reconstructed vagina
should be able to accommodate two fingers. If the atretic segment is short and the wound
is small, the vestibular mucosa can be sutured to the vaginal upper segment mucosa to
create a continuous vaginal canal. For larger wounds, after hemostasis, a mold, amniotic
membrane, or artificial biological graft can be used as a stent, and the area will be left to
epithelialize postoperatively.
A modified “balloon vaginoplasty” provides a novel treatment option for patients
with distal vaginal atresia. Initially developed by Saman et al. in 2009, balloon vaginoplasty
differs from the traditional “cut-through” approach that involves dissection of the vesicorec-
tal space [
41
,
42
]. The key feature of this technique is the use of a soft, non-erosive Foley
balloon for traction, allowing the creation of a new vaginal canal by expanding the natural
vaginal mucosa without dissecting the vesicorectal space [
43
–
45
]. Although Saman et al.
demonstrated the adaptability of balloon vaginoplasty for various sacroiliac abnormalities,
they did not specifically apply this method to patients diagnosed with vaginal atresia,
nor did they clarify if this technique could effectively expand the distal vagina or thin the
septum to reduce the risk of stenosis.
Building on this foundation, Zhang et al. modified balloon vaginoplasty in a 2022
study, demonstrating its ability to further expand the distal vagina and thin the septum
in patients with vaginal atresia, reducing the risk of stenosis [
46
]. This modification
provides a new option for patients with distal vaginal atresia, particularly those with
obstructions
≥
3 cm in length. Specifically, the method recommends a two-stage surgical
approach. In the first stage, the surgeon inserts a Foley catheter through the obstructed
vaginal canal until it reaches the hematocolpos in the upper vagina, inflating the balloon
with 30–50 mL of saline to provide traction. The patient, with parental assistance, continues
traction at home, pulling down the catheter by at least 1 cm each time, 6–8 times daily for
5–10 min per session, until only 1 cm of the obstruction remains.
The second stage involves the surgeon pulling down the balloon and making a “Z”-
shaped incision to open the atretic vaginal segment, followed by postoperative stent
placement to prevent retraction. Zhang et al. reported that the modified vaginoplasty was
successful in patients with distal vaginal atresia, with no intraoperative complications and
satisfactory postoperative outcomes.
5.2. Surgical Approaches for Complete Vaginal Atresia
Complete vaginal atresia is often associated with cervical dysgenesis, and the primary
consideration in treatment is the possibility of preserving the uterus. If uterine preservation
is feasible and the patient and family strongly desire to retain fertility, they should be
fully informed about the extremely low postoperative pregnancy rate [
47
]. The surgery to
preserve reproductive function involves creating a cervical-like canal between the uterus

Biomedicines 2025,13, 128 7 of 14
and vagina to allow unobstructed menstrual flow. With advances in surgical techniques
and new materials, an increasing number of successful cases of fertility-preserving surg-
eries have been reported. In general, these procedures are divided into cervicovaginal
canalization and uterovaginal anastomosis.
Cervicovaginal canalization involves creating a channel through the dense fibrous
tissue between the uterine cavity and vagina. After the surgery, a cervical stent and vaginal
mold are typically placed to prevent re-adhesion of the newly formed cervix and vagina [
48
].
Uterovaginal anastomosis is primarily used in cases with complete cervical atresia or when
cervical tissue is insufficient for formation. This procedure entails the thorough dissection
of the uterorectal and vesicouterine spaces, removal of dysplastic cervical tissue, and
downward mobilization of the uterus, which is then anastomosed to the newly formed
vaginal or vestibular mucosa [
49
]. A cervical catheter is often placed within the anastomotic
site to ensure drainage and prevent adhesions.
Thirty-three studies have reported outcomes of cervicovaginal anastomosis in 53 pa-
tients with cervical and vaginal atresia. Of these, 33 patients (62.3%) resumed menstruation
postoperatively, with one patient achieving natural pregnancy. Twelve patients experi-
enced re-obstruction, and four died due to septic shock. Additionally, 21 studies reported
outcomes of uterovaginal anastomosis in 121 patients, 92 of whom had cervical atresia
with partial or complete vaginal atresia. Postoperatively, 94 patients (77.7%) resumed
menstruation, with 6 achieving natural pregnancy. Eight patients experienced various
complications; one developed a ureterovaginal fistula, and seven eventually underwent
hysterectomy due to complications.
Lastly, studies indicate that postoperative vaginal stenosis is common following surgi-
cal correction of vaginal atresia, especially in patients with longer obstruction distances [
48
].
Therefore, regardless of the technique and materials used for reconstruction, the use of a
vaginal dilator or mold for at least six months postoperatively is crucial to prevent vaginal
stenosis and re-obstruction [
50
,
51
]. Patients who regularly used vaginal dilators postopera-
tively achieved significantly longer vaginal lengths and more satisfactory sexual outcomes
compared to those with irregular usage [52].
5.3. Postoperative Care
The frequency of vaginal dilation or use of vaginal molds post-surgery depends on
the length of the atretic vagina, in order to prevent re-closure or stenosis. A vaginal mold
should be used regularly until the vaginal wound is fully epithelialized, which may take 3
to 6 months or longer, after which it can be used intermittently or replaced by self-dilation
until regular sexual activity is resumed.
6. Applications and Advances of Different Materials in Upper
Vaginal Atresia
For patients with high-level vaginal atresia, a lining for the newly constructed vagina
is often required to promote epithelialization. Various materials have been used as vaginal
coverings in vaginoplasty, including skin flaps, amniotic membrane, peritoneum, intestinal
segments, oral mucosa, and biological grafts [
53
]. However, skin flaps are less commonly
used today due to esthetic concerns, and oral mucosa is rarely applied in vaginal atresia
cases. Currently, commonly used materials include an amniotic membrane, peritoneum,
intestinal segments, and biological grafts. Advances and challenges of different materials
in vaginal atresia are summarized in Table 2.

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Table 2. Advances and challenges of different materials in upper vaginal atresia.
Vaginoplasty Technique Advantages Challenges/Considerations
Biological Graft Vaginoplasty
Promising in tissue engineering,
provides ECM-like environment for
cell adhesion and remodeling.
Still experimental, lack of long-term
sexual satisfaction data.
Peritoneal Vaginoplasty
Cost-effective, high patient
satisfaction, efficient. Can be carried
out via open surgery, vaginal, or
laparoscopic approach.
Postoperative complications in some
cases, need for postoperative
interventions to enhance
sexual quality.
Intestinal Vaginoplasty
Self-lubricating, growth-compatible
for prepubescent patients, low risk
of stenosis.
Invasive surgery, complications in
some cases, pregnancy outcomes
not reported.
Amniotic Membrane Vaginoplasty
Affordable, safe, simple, minimal
scarring and infection, suitable for
resource-limited settings.
Long-term functional restoration not
fully achieved, particularly for
congenital vaginal atresia.
6.1. Biological Graft Vaginoplasty
In tissue engineering, extracellular matrix (ECM) materials are being explored for vaginal
reconstruction. These materials provide an ECM-like environment for vaginal cell adhesion,
ECM secretion, and host cell remodeling [
54
]. Although ECM-based grafts show promise, they
remain largely experimental [
55
]. The only specific biological graft application reported for
vaginal atresia patients involves the work of Papastefan et al., who utilized a small intestinal
submucosa (SIS) ECM for vaginoplasty [
56
]. Their study indicated that SIS is an effective and
safe alternative for vaginal reconstruction, with low perioperative morbidity and no need for
long-term mold usage, while maintaining functional vaginal length. Following the creation of
a neovaginal space, the SIS ECM was wrapped in a silicone mold, which was removed on
the seventh postoperative day. The median surgery duration was 171 min, with an estimated
blood loss of 10 mL and a 2-day hospital stay. At the last follow-up, the average vaginal
length was 8.97 cm, with all patients successfully progressing to self-dilation or intercourse to
maintain patency. However, the study lacked detailed outcomes on sexual satisfaction and
comparison with alternative techniques.
6.2. Peritoneal Vaginoplasty
In peritoneal vaginoplasty, the peritoneum, along with portions of the bladder and
rectal serosa, is used to cover the newly constructed vaginal surface. This approach is
cost-effective and efficient, with high patient satisfaction regarding sexual quality, which
can be further enhanced with postoperative interventions [
57
]. Peritoneal vaginoplasty
can be performed via open surgery, vaginal approach, or laparoscopic approach. A recent
prospective study reported outcomes of laparoscopic peritoneal vaginoplasty in nine
patients with congenital cervical and complete vaginal atresia, using peritoneal flaps and
cervical reconstruction. After a median follow-up of 48 months, the median neovaginal
length was 7.5 cm, with three cases of postoperative complications that were resolved
with appropriate treatment. All married patients reported satisfaction with their sexual
experience, further demonstrating the suitability of the peritoneal approach for complete
vaginal atresia patients [58].
6.3. Intestinal Vaginoplasty
Intestinal vaginoplasty has several advantages, including self-lubrication, growth
compatibility for prepubescent patients, and a minimal risk of stenosis [
59
]. Traditionally,
intestinal vaginoplasty has been performed via open surgery, but recent innovations include

Biomedicines 2025,13, 128 9 of 14
robot-assisted ileal vaginoplasty. One report described a robot-assisted ileal vaginoplasty
after failed oral mucosa vaginoplasty in a patient with vaginal atresia. The procedure,
performed through a combined abdominoperineal approach, resulted in successful recovery,
and cystoscopy at 2 weeks, 3 months, and 1 year postoperatively confirmed adequate
vaginal depth and successful expansion [
60
]. Some authors also propose reconstructing
the vagina with an ascending colon segment, using the appendix to reconstruct the cervix.
In this approach, the appendix connects the neovagina and uterus, maintaining cervical
glands that may resist infection. This setup allows menstrual flow through the neovagina
and enables sperm entry to the uterus, though pregnancy outcomes were not reported [
61
].
6.4. Amniotic Membrane Vaginoplasty
Amniotic membrane vaginoplasty is an affordable, safe, and simple technique that re-
constructs or repairs vaginal structures using the amnion (a component of fetal membranes)
as a biological material [
62
]. This method has a high success rate, with low postoperative
pain, infection, and scarring, making it especially beneficial in resource-limited countries.
Avsar et al. reported successful outcomes using human amniotic membrane in patients
with vaginal atresia [
63
]. However, long-term follow-up showed that the McIndoe tech-
nique combined with amniotic membrane grafting did not fully restore normal vaginal
function and anatomy in cases of congenital vaginal atresia [
64
]. Only one case of amniotic
membrane vaginoplasty for a 15-year-old girl with vaginal atresia and cervical dysgenesis
has been reported, though long-term follow-up data for this case is lacking [65].
7. Treatment for Patients with Co-Occurring Anomalies
For patients with coexisting anomalies such as rectovaginal fistula or anal atresia,
the anatomical structures in proximity to vaginal atresia require careful consideration in
surgical planning. Kisku et al., in a review of seven cases, emphasized the importance of
appropriate timing and surgical approach when managing combined rectovaginal fistula
and vaginal atresia. They suggested using the rectovaginal fistula as a new anus rather
than a neovagina and advocated for delayed intestinal vaginoplasty to better assess uterine
function [
66
]. Similarly, Pandya et al. explored the joint issue of vaginal and anal atresia,
noting that while surgical repair generally yielded satisfactory outcomes, long-term bowel
control often remained suboptimal [
67
]. Skerritt et al., through a literature review, evaluated
the long-term reproductive and sexual function in patients with anorectal malformations
and vaginal atresia, highlighting the need for more long-term data to support the superiority
of specific vaginal replacement techniques [68].
8. Psychological Status
The bidirectional relationship between psychological issues and sexual dysfunction
in patients with vaginal atresia has long attracted scholarly attention [
69
]. Specifically,
sexual function scores are positively correlated with self-esteem scores and negatively
correlated with depression and anxiety scores. As a condition impacting female sexual
function, vaginal atresia also significantly affects the psychological state of patients. Studies
have shown that among all patients diagnosed with complete vaginal atresia, 58.7% exhibit
moderate to severe depressive symptoms. Factors associated with depressive symptoms
in patients with complete vaginal atresia include age, parental attitudes, familial discord,
peer bullying, sexual dysfunction, fertility anxiety, and discomfort associated with vaginal
molds [
70
]. Although patients with distal vaginal atresia in China have been reported to
attend mainstream schools and live independently [
8
], there is currently a lack of in-depth
studies regarding their psychological status. During the treatment process, vaginal atresia
patients require psychological preparation when using vaginal dilators postoperatively.

Biomedicines 2025,13, 128 10 of 14
Furthermore, patients with MRKH syndrome, which shares phenotypic similarities with
vaginal atresia [
71
,
72
], are significantly affected by reproductive tract anomalies, exhibiting
characteristics such as low self-esteem and depressive symptoms. Research indicates that
preoperatively, 45.3% of patients report mild to moderate depression, while 34.0% report
mild anxiety. Follow-up studies approximately three years postoperation show that while
patients’ sexual arousal levels have significantly improved, their psychological health
has not seen substantial improvement [
72
]. These findings underscore the importance
of addressing the psychological state of vaginal atresia patients in both assessment and
treatment, indicating that psychological intervention should play a critical role in their care.
Psychological counseling can not only assist patients in coping with the psychological stress
associated with their condition but also provide essential support before and after surgery,
enhancing their confidence in treatment and offering avenues for adjusting expectations
and accepting reality. Future research should further explore optimized approaches to
psychological intervention, assess the long-term impacts of different methods on patients’
psychological states, and investigate how to better integrate these interventions into existing
treatment plans for comprehensive physical and psychological rehabilitation.
9. Fertility Outcomes and Sexual Function
The fertility outcomes and sexual function of patients with vaginal atresia are important
indicators for assessing treatment efficacy and quality of life. For patients with distal vaginal
atresia, the relatively mild nature of the condition allows for surgical restoration of the vagina,
which is usually sufficient to support sexual activity, with most patients achieving natural
conception and experiencing unaffected pregnancy outcomes. In contrast, patients with
complete vaginal atresia face potential complications due to cervical development anomalies,
as well as surgical considerations regarding whether to excise the uterus and the specific
method of vaginal formation, leading to less optimistic fertility outcomes [
73
]. Research
by Reham et al. indicates that only 28.5% of patients with cervical-vaginal atresia achieved
clinical pregnancy postoperatively, with a mere 14% resulting in live births [
74
]. Nonetheless,
efforts to enhance fertility outcomes in patients with complete vaginal atresia continue. Recent
studies indicate that vaginoplasty combined with cervical-vaginal anastomosis has a protective
effect on the fertility of patients with complete vaginal atresia accompanied by cervical canal
obstruction. For vaginal atresia patients with well-developed uteri and a desire for fertility,
cervical-vaginal anastomosis should be prioritized [
75
]. Additionally, even patients who
undergo vaginoplasty can improve their intrauterine environment prior to
in vitro
fertilization–
embryo transfer (IVF-ET) through hysteroscopic evaluation and uterine dilation, ultimately
achieving favorable pregnancy outcomes [
76
]. These findings suggest that advancements
in surgical techniques and collaboration among gynecological, obstetric, reproductive, and
neonatal departments may lead to continuous improvements in pregnancy outcomes for
patients with cervical-vaginal atresia.
10. Conclusions and Future Directions
This paper reviews the epidemiology of vaginal atresia, exploring its causes from
developmental, genetic, and environmental perspectives. It highlights the role of genetic
susceptibility and environmental interactions in disease manifestation. The article summa-
rizes clinical features, diagnostic methods, and treatment strategies for distal and complete
vaginal atresia, as well as important case studies and recent clinical research. Psychologi-
cal issues, fertility outcomes, and sexual function are also examined. While research has
covered clinical symptoms and diagnoses well, there is a lack of focus on genetic factors,
treatment options, and patient psychological states, which requires further investigation.

Biomedicines 2025,13, 128 11 of 14
Genetic studies have identified several genes, including those from the TBX and Tyro3
RTK families, as contributors to vaginal atresia, though the exact mechanisms remain
unclear. Larger cohort studies and animal models, such as gene knockout mice, are needed
to explore other genetic factors and their pathways. Additionally, technologies like whole-
exome and whole-genome sequencing offer valuable tools for exploring complex genetic
backgrounds, which could enable the identification of genetic variants associated with
vaginal atresia and facilitate the discovery of new pathogenic genes to better elucidate the
disease’s pathogenesis, and furthermore inform genetic testing and targeted therapies in
the future.
Regarding treatment, various surgical options exist, but large-scale studies and random-
ized controlled trials (RCTs) are lacking to determine the most effective and long-lasting
interventions. Future research should focus on optimizing treatment protocols and exploring
new biomaterials for vaginal reconstruction, with the goal of improving patient outcomes.
The psychological impact on patients with vaginal atresia, including coping with
their condition and social pressures, is another important area that requires more attention.
Incorporating psychological support into treatment plans is crucial. Furthermore, while
pregnancy outcomes for these patients are often poor, especially for those with complete
vaginal atresia, long-term follow-up studies are needed to explore influencing factors and
improve reproductive health.
In conclusion, research on vaginal atresia should address genetic factors, treatment
strategies, and the impact on patients’ psychological well-being and fertility outcomes. By
advancing understanding in these areas, we can improve treatment and enhance patient
quality of life.
Author Contributions: X.L. was involved in manuscript drafting. J.K. and L.Z. participated in the
study design and revision of the manuscript. All authors have read and agreed to the published
version of the manuscript.
Funding: This study received financial support from the National Natural Science Foundation of
China (No. 82101696 and 82271656), the National Key Research and Development Program of China
(No. 2021YFC2701400), and the collaborative Mobility project from the Sino-German Center for
Research Promotion (No. M-0110).
Conflicts of Interest: The authors declare no conflicts of interest.
References
1.
Robboy, S.J.; Kurita, T.; Baskin, L.; Cunha, G.R. New insights into human female reproductive tract development. Differentiation
2017,97, 9–22. [CrossRef] [PubMed]
2.
Xu, S.; Zhang, J.; Wang, S.; Yang, L.; Qian, J.; Yue, S.; Zhu, D.; Yang, L.; Zhao, L.; Yang, A.; et al. MRI features and differential
diagnoses of congenital vaginal atresia. Gynecol. Endocrinol. 2019,35, 777–781. [CrossRef]
3.
Grimbizis, G.F.; Gordts, S.; Di Spiezio Sardo, A.; Brucker, S.; De Angelis, C.; Gergolet, M.; Li, T.C.; Tanos, V.; Brolmann, H.;
Gianaroli, L.; et al. The ESHRE-ESGE consensus on the classification of female genital tract congenital anomalies. Gynecol. Surg.
2013,10, 199–212. [CrossRef]
4.
Xie, Z.; Zhang, X.; Zhang, N.; Xiao, H.; Liu, Y.; Liu, J.; Chen, L.; Li, L.; Zhang, L.; Zhang, Y. Clinical features and surgical
procedures of congenital vaginal atresia-A retrospective study of 67 patients. Eur. J. Obstet. Gynecol. Reprod. Biol. 2017,217,
167–172. [CrossRef] [PubMed]
5.
Zhu, L.; Lang, J.H.; Song, L. The Chinese Expert Consensus on the Diagnosis and Treatment of Herlyn-Werner-Wunderlich
Syndrome, MRKH Syndrome, and Vaginal Atresia. Chin. J. Obstet. Gynecol. 2018,53, 35–42.
6.
Bryan, A.L.; Nigro, J.A.; Counseller, V.S. One hundred cases of congenital absence of the vagina. Surg. Gynecol. Obstet. 1949,88,
79–86.
7.
Reindollar, R.H.; Byrd, J.R.; McDonough, P.G. Delayed sexual development: A study of 252 patients. Am. J. Obstet. Gynecol. 1981,
140, 371–380. [CrossRef]
8.
Kang, J.; Zhou, Q.; Chen, N.; Liu, Z.; Zhang, Y.; Sun, J.; Ma, C.; Chen, F.; Ma, Y.; Wang, L.; et al. Clinical and Genetic Characteristics
of a Cohort with Distal Vaginal Atresia. Int. J. Mol. Sci. 2022,23, 12853. [CrossRef]

Biomedicines 2025,13, 128 12 of 14
9. Yin, Y.; Ma, L. Development of the mammalian female reproductive tract. J. Biochem. 2005,137, 677–683. [CrossRef]
10.
Cai, Y. Revisiting old vaginal topics: Conversion of the Mullerian vagina and origin of the “sinus” vagina. Int. J. Dev. Biol. 2009,
53, 925–934. [CrossRef] [PubMed]
11. Bloomfield, A. The Development of the Lower End of the Vagina. J. Anat. 1927,62, 9–32.
12.
Sanchez-Ferrer, M.L.; Acien, M.I.; Sanchez del Campo, F.; Mayol-Belda, M.J.; Acien, P. Experimental contributions to the study of
the embryology of the vagina. Hum. Reprod. 2006,21, 1623–1628. [CrossRef] [PubMed]
13.
Aswani, Y.; Varma, R.; Choudhary, P.; Gupta, R.B. Wolffian Origin of Vagina Unfolds the Embryopathogenesis of OHVIRA
(Obstructed Hemivagina and Ipsilateral Renal Anomaly) Syndrome and Places OHVIRA as a Female Counterpart of Zinner
Syndrome in Males. Pol. J. Radiol. 2016,81, 549–556. [CrossRef]
14. Kurita, T. Developmental origin of vaginal epithelium. Differentiation 2010,80, 99–105. [CrossRef]
15.
Hughes, I.A.; Davies, J.D.; Bunch, T.I.; Pasterski, V.; Mastroyannopoulou, K.; MacDougall, J. Androgen insensitivity syndrome.
Lancet 2012,380, 1419–1428. [CrossRef]
16.
Auer, M.K.; Nordenstrom, A.; Lajic, S.; Reisch, N. Congenital adrenal hyperplasia. Lancet 2023,401, 227–244. [CrossRef] [PubMed]
17.
Chu, C.; Li, L.; Lu, D.; Duan, A.H.; Luo, L.J.; Li, S.; Yin, C. Whole-Exome Sequencing Identified a TBX6 Loss of Function Mutation
in a Patient with Distal Vaginal Atresia. J. Pediatr. Adolesc. Gynecol. 2019,32, 550–554. [CrossRef]
18.
Davenport, T.G.; Jerome-Majewska, L.A.; Papaioannou, V.E. Mammary gland, limb and yolk sac defects in mice lacking Tbx3, the
gene mutated in human ulnar mammary syndrome. Development 2003,130, 2263–2273. [CrossRef]
19.
Frank, D.U.; Emechebe, U.; Thomas, K.R.; Moon, A.M. Mouse Tbx3 mutants suggest novel molecular mechanisms for Ulnar-
mammary syndrome. PLoS ONE 2013,8, e67841. [CrossRef] [PubMed]
20.
Wu, H.; Tang, H.; Chen, Y.; Wang, H.; Han, D. High incidence of distal vaginal atresia in mice lacking Tyro3 RTK subfamily. Mol.
Reprod. Dev. 2008,75, 1775–1782. [CrossRef]
21.
Zhao, F.; Zhou, J.; Li, R.; Dudley, E.A.; Ye, X. Novel function of LHFPL2 in female and male distal reproductive tract development.
Sci. Rep. 2016,6, 23037. [CrossRef]
22.
Lin, X.; Wang, C.; Zhang, Q.; Pan, Y.H.; Dang, S.; Zhang, W. ADAMTS18 regulates vaginal opening through influencing the fusion
of Mullerian duct and apoptosis of vaginal epithelial cells in mice. Reprod. Biol. 2021,21, 100537. [CrossRef] [PubMed]
23.
Kato, N.; Motoyama, T. Expression of hepatocyte nuclear factor-1beta in human urogenital tract during the embryonic stage.
Anal. Quant. Cytol. Histol. 2009,31, 34–40. [PubMed]
24.
Bingham, C.; Ellard, S.; Cole, T.R.; Jones, K.E.; Allen, L.I.; Goodship, J.A.; Goodship, T.H.; Bakalinova-Pugh, D.; Russell, G.I.;
Woolf, A.S.; et al. Solitary functioning kidney and diverse genital tract malformations associated with hepatocyte nuclear factor-1beta
mutations. Kidney Int. 2002,61, 1243–1251. [CrossRef]
25.
Kato, N.; Motoyama, T. Hepatocyte nuclear factor-1beta (HNF-1beta) in human urogenital organs: Its expression and role in
embryogenesis and tumorigenesis. Histol. Histopathol. 2009,24, 1479–1486.
26.
Qiu, J.J.; Chang, X.Y.; Zhang, N.; Guo, L.P.; Wang, S.; Gu, W.Y.; Yin, Y.M.; Shi, Z.W.; Hua, K.Q. Genetic variation and molecular
profiling of congenital malformations of the female genital tract based on whole-genome sequencing. World J. Pediatr. 2024,20,
1179–1195. [CrossRef] [PubMed]
27.
Kyei-Barffour, I.; Margetts, M.; Vash-Margita, A.; Pelosi, E. The Embryological Landscape of Mayer-Rokitansky-Kuster-Hauser
Syndrome: Genetics and Environmental Factors. Yale J. Biol. Med. 2021,94, 657–672.
28.
Dural, O.; Ugurlucan, F.G.; Yasa, C.; Bastu, E.; Eren, H.; Yuksel, B.; Celik, S.; Akhan, S.E. A Case of Distal Vaginal Agenesis
Presenting with Recurrent Urinary Tract Infection and Pyuria in a Prepubertal Girl. J. Pediatr. Adolesc. Gynecol. 2017,30, e7–e10.
[CrossRef] [PubMed]
29.
Freytag, D.; Mettler, L.; Maass, N.; Gunther, V.; Alkatout, I. Uterine anomalies and endometriosis. Minerva Med. 2020,111, 33–49.
[CrossRef]
30.
Sanfilippo, J.S.; Wakim, N.G.; Schikler, K.N.; Yussman, M.A. Endometriosis in association with uterine anomaly. Am. J. Obstet.
Gynecol. 1986,154, 39–43. [CrossRef]
31.
Kapczuk, K.; Zajaczkowska, W.; Madziar, K.; Kedzia, W. Endometriosis in Adolescents with Obstructive Anomalies of the
Reproductive Tract. J. Clin. Med. 2023,12, 2007. [CrossRef]
32.
Globa, E.; Zelinska, N.; Siryk, N.; Bashamboo, A.; McElreavey, K. Atypical Clinical Presentation of Persistent Mullerian Duct
Syndrome in Siblings. Sex. Dev. 2020,14, 27–32. [CrossRef] [PubMed]
33.
Elsherbeny, M.; Abdelhay, S.; Mousa, M. Neonatal Single-Stage Surgical Management of Complicated Distal Vaginal Atresia:
Revisiting an Appropriate and Feasible Technique. J. Pediatr. Adolesc. Gynecol. 2024,37, 63–66. [CrossRef]
34.
Grimbizis, G.F.; Campo, R. Congenital malformations of the female genital tract: The need for a new classification system. Fertil.
Steril. 2010,94, 401–407. [CrossRef] [PubMed]
35.
Graupera, B.; Pascual, M.A.; Hereter, L.; Browne, J.L.; Ubeda, B.; Rodriguez, I.; Pedrero, C. Accuracy of three-dimensional
ultrasound compared with magnetic resonance imaging in diagnosis of Mullerian duct anomalies using ESHRE-ESGE consensus
on the classification of congenital anomalies of the female genital tract. Ultrasound Obs. Gynecol. 2015,46, 616–622. [CrossRef]

Biomedicines 2025,13, 128 13 of 14
36.
Lazanyi, M.; Grover, S.R. Imperforate hymen: Retrospective review from a single tertiary centre of presenting symptoms and
diagnostic process. J. Paediatr. Child Health. 2020,56, 90–93. [CrossRef]
37.
Chen, N.; Song, S.; Bao, X.; Zhu, L. Update on Mayer-Rokitansky-Kuster-Hauser syndrome. Front. Med. 2022,16, 859–872.
[CrossRef]
38.
Li, Y.; Ehiri, J.; Tang, S.; Li, D.; Bian, Y.; Lin, H.; Marshall, C.; Cao, J. Factors associated with patient, and diagnostic delays in
Chinese TB patients: A systematic review and meta-analysis. BMC Med. 2013,11, 156. [CrossRef]
39.
Darebo, T.D.; Spigt, M.; Teklewold, B.; Badacho, A.S.; Mayer, N.; Teklewold, M. The sexual and reproductive healthcare challenges
when dealing with female migrants and refugees in low and middle-income countries (a qualitative evidence synthesis). BMC
Public Health 2024,24, 520. [CrossRef] [PubMed]
40.
Amies Oelschlager, A.M.E.; Berger-Chen, S.W. Management of Acute Obstructive Uterovaginal Anomalies: ACOG Committee
Opinion, Number 779. Obstet. Gynecol. 2019,133, e363–e371.
41.
El Saman, A.M.; Zakherah, M.S.; Nasr, A.M.; Fathalla, M.M. Distension versus traction in laparoscopically assisted balloon
vaginoplasty for management of vaginal aplasia. Int. J. Gynaecol. Obstet. 2009,104, 72–73. [CrossRef] [PubMed]
42.
El Saman, A.M. Combined retropubic balloon vaginoplasty and laparoscopic canalization: A novel blend of techniques provides
a minimally invasive treatment for cervicovaginal aplasia. Am. J. Obstet. Gynecol. 2009,201, 333.e1–333.e5. [CrossRef] [PubMed]
43.
El Saman, A.M. Retropubic balloon vaginoplasty for management of Mayer-Rokitansky-Kuster-Hauser syndrome. Fertil. Steril.
2010,93, 2016–2019. [CrossRef]
44.
El Saman, A.M.; Ismael, A.M.; Zakherah, M.S.; Nasr, A.; Tawfik, R.M.; Bedaiwy, M.A. Enhancement balloon vaginoplasty for
treatment of blind vagina due to androgen insensitivity syndrome. Fertil. Steril. 2011,95, 779–782. [CrossRef] [PubMed]
45. El Saman, A.M.; Saad, H.; Hassanin, A.I.; Shokery, M.; Abdelghaffar, H.M. Inverted balloon vaginoplasty: An obstructed upper
vaginal pouch was pulled downward to form a neovagina. Am. J. Obstet. Gynecol. 2012,206, 267.e1–267.e4. [CrossRef] [PubMed]
46.
Zhang, M.; Meng, L.; Du, Y.; Zhao, J.; Li, Z.; Liu, S.; Huang, X. Modified balloon vaginoplasty for high position vaginal atresia.
Pediatr. Surg. Int. 2022,38, 631–635. [CrossRef]
47.
Rock, J.A.; Roberts, C.P.; Jones, H.W., Jr. Congenital anomalies of the uterine cervix: Lessons from 30 cases managed clinically by
a common protocol. Fertil. Steril. 2010,94, 1858–1863. [CrossRef] [PubMed]
48.
Kang, J.; Chen, N.; Zhang, Y.; Ma, C.; Ma, Y.; Wang, Y.; Tian, W.; Zhu, L. Laparoscopically Assisted Uterovaginal Canalization
and Vaginoplasty for Patients with Congenital Cervical and Vaginal Atresia: A Step-by-step Guide and Long-term Outcomes. J.
Minim. Invasive Gynecol. 2021,28, 1203–1210. [CrossRef]
49.
Candiani, M.; Vercellini, P.; Fedele, F.; Parma, M.; Salvatore, S.; Fedele, L. Long-Term Follow-Up after Laparoscopic Uterovestibular
Anastomosis in Patients with Cervical Atresia and Complete Absence of the Vagina. J. Pediatr. Adolesc. Gynecol. 2023,36, 72–78.
[CrossRef]
50.
Skinner, B.; Quint, E.H. Obstructive Reproductive Tract Anomalies: A Review of Surgical Management. J. Minim. Invasive Gynecol.
2017,24, 901–908. [CrossRef]
51.
Mansouri, R.; Dietrich, J.E. Postoperative Course and Complications after Pull-through Vaginoplasty for Distal Vaginal Atresia. J.
Pediatr. Adolesc. Gynecol. 2015,28, 433–436. [CrossRef]
52.
Bastu, E.; Akhan, S.E.; Mutlu, M.F.; Nehir, A.; Yumru, H.; Hocaoglu, E.; Gungor-Ugurlucan, F. Treatment of vaginal agenesis
using a modified McIndoe technique: Long-term follow-up of 23 patients and a literature review. Can. J. Plast. Surg. 2012,20,
241–244. [CrossRef]
53.
Sueters, J.; Groenman, F.A.; Bouman, M.B.; Roovers, J.P.W.; de Vries, R.; Smit, T.H.; Huirne, J.A.F. Tissue Engineering Neovagina
for Vaginoplasty in Mayer-Rokitansky-Kuster-Hauser Syndrome and Gender Dysphoria Patients: A Systematic Review. Tissue
Eng. Part. B Rev. 2023,29, 28–46. [CrossRef] [PubMed]
54.
Robinson, J.; Shikanov, A.; Harley, B. Special Issue on Tissue Engineering for Women’s Health. Tissue Eng. Part. A 2020,26,
685–687. [CrossRef]
55.
Farzamfar, S.; Elia, E.; Richer, M.; Chabaud, S.; Naji, M.; Bolduc, S. Extracellular Matrix-Based and Electrospun Scaffolding
Systems for Vaginal Reconstruction. Bioengineering 2023,10, 790. [CrossRef] [PubMed]
56.
Papastefan, S.T.; Collins, S.A.; Mueller, M.G.; Geynisman-Tan, J.; Reynolds, M.; Cheng, E.Y.; Yerkes, E.B.; Grabowski, J.E.
Successful Use of Acellular Small Intestinal Submucosa Graft in Vaginal Reconstruction. J. Pediatr. Surg. 2024,59, 124–128.
[CrossRef]
57.
Martens, L.; Tannenbaum, L.; Van Kuijk, S.M.J.; Notten, K.J.B.; Kluivers, K.B. Laparoscopic Davydov vs. laparoscopic Vecchietti
neovaginoplasty in women with Mayer-Rokitansky-Kuster-Hauser syndrome; a systematic review and meta-analysis. Fertil.
Steril. 2024,121, 679–692. [CrossRef] [PubMed]
58.
Liu, H.; Zhang, H.; Wang, C.; Dang, Q. Efficacy and safety of laparoscopic vaginoplasty with peritoneal flaps and cervicoplasty in
patients with congenital cervical and complete vaginal atresia: A pilot study. Quant. Imaging Med. Surg. 2024,14, 3121–3130.
[CrossRef] [PubMed]

Biomedicines 2025,13, 128 14 of 14
59. Karateke, A.; Haliloglu, B.; Parlak, O.; Cam, C.; Coksuer, H. Intestinal vaginoplasty: Seven years’ experience of a tertiary center.
Fertil. Steril. 2010,94, 2312–2315. [CrossRef]
60.
Gundeti, M.S.; Kumar, R.; Mohammad, M. Robotic assisted ileo-vaginoplasty for vaginal atresia. J. Pediatr. Urol. 2021,17, 273–274.
[CrossRef] [PubMed]
61.
Agarwal, M.; Sinha, S.; Sinha, U.; Sinha, S.; Simran, S. Laparoscopic-assisted neo-cervico-vaginal anastomosis and neo-vagina
creation in congenital atresia: A retrospective study measuring the outcome and success. J. Plast. Reconstr. Aesthet. Surg. 2024,90,
350–356. [CrossRef]
62. Piazza, M.J. Study and evaluation of neovagina epithelium. JBRA Assist. Reprod. 2021,25, 581–585. [CrossRef] [PubMed]
63.
Avsar, A.F.; Tas, E.E.; Keskin, H.L.; Yegin, G.F. Vaginoplasty Using Human Amniotic Membranes A Report of Five Patients. J.
Reprod. Med. 2016,61, 483–488. [PubMed]
64.
Dadhwal, R.; Nayyar, R.; Krishna, A.; Kumar, P. Laparoscopic sigmoid vaginoplasty: A salvage option for genitourinary fistula
after failed McIndoe’s repair. BMJ Case Rep. 2020,13, e235297. [CrossRef] [PubMed]
65.
Regmi, D.R.; Dangal, G.; Karki, A.; Pradhan, H.K.; Shrestha, R.; Bhattachan, K.; Tiwari, K.D.; Bharati, S.; Manandhar, P.; Maharjan,
S. Vaginal Atresia with Cervical Agenesis, a Rare Congenital Malformation. Kathmandu Univ. Med. J. 2021,19, 390–392. [CrossRef]
66.
Kisku, S.; Barla, R.K.; Sen, S.; Karl, S.; Mathai, J.; Varghese, L. Rectovestibular fistula with vaginal atresia: Our experience and a
proposed course of management. Pediatr. Surg. Int. 2014,30, 633–639. [CrossRef] [PubMed]
67.
Pandya, K.A.; Koga, H.; Okawada, M.; Coran, A.G.; Yamataka, A.; Teitelbaum, D.H. Vaginal anomalies and atresia associated
with imperforate anus: Diagnosis and surgical management. J. Pediatr. Surg. 2015,50, 431–437. [CrossRef] [PubMed]
68.
Skerritt, C.; Vilanova Sanchez, A.; Lane, V.A.; Wood, R.J.; Hewitt, G.D.; Breech, L.L.; Levitt, M. Menstrual, Sexual, and Obstetrical
Outcomes after Vaginal Replacement for Vaginal Atresia Associated with Anorectal Malformation. Eur. J. Pediatr. Surg. 2017,27,
495–502. [CrossRef]
69.
Atlantis, E.; Sullivan, T. Bidirectional association between depression and sexual dysfunction: A systematic review and meta-
analysis. J. Sex. Med. 2012,9, 1497–1507. [CrossRef]
70.
Liu, X.; Ding, J.; Li, Y.; Hua, K.; Zhang, X. An Investigation of Depressive Symptoms in Patients with Congenital Cervical and
Vaginal Aplasia: A Cross-Sectional Study. Int. J. Womens Health 2022,14, 1621–1627. [CrossRef]
71.
Lei, X.-H.; Wang, X.; Shao, S.-Y.; Hua, K.-Q.; Zhang, Y. Self-esteem, depression, anxiety and sexual function in Mayer-Rokitansky-
Kuster-Hauser syndrome with neovagina: A case series. Eur. J. Obstet. Gynecol. Reprod. Biol. 2024,298, 85–90. [CrossRef]
[PubMed]
72.
Chen, N.; Song, S.; Duan, Y.; Kang, J.; Deng, S.; Pan, H.; Zhu, L. Study on depressive symptoms in patients with Mayer-Rokitansky-
Kuster-Hauser syndrome: An analysis of 141 cases. Orphanet J. Rare Dis. 2020,15, 121. [CrossRef]
73.
Fedele, F.; Parazzini, F.; Vercellini, P.; Bergamini, V.; Fedele, L. Reconstructive surgery for congenital atresia of the uterine cervix:
A systematic review. Arch. Gynecol. Obstet. 2023,308, 685–700. [CrossRef] [PubMed]
74.
Fouad, R.; Zayed, M. Utero-vaginal anastomosis in cases of cervical malformations: Long-term follow-up and fertility challenges.
Arch. Gynecol. Obstet. 2023,307, 1001–1006. [CrossRef] [PubMed]
75.
Mei, L.; Zhang, H.; Chen, Y.; Niu, X. Clinical features of congenital complete vaginal atresia combined with cervical aplasia: A
retrospective study of 19 patients and literature review. Congenit. Anom. 2021,61, 127–132. [CrossRef] [PubMed]
76.
Zhu, L.; Chen, N. New concepts in the diagnosis, treatment and fertility of female genital tract malformations. Chin. J. Obstet.
Gynecol. 2024,59, 343–345.
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