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Advances in Drug Delivery to the Reproductive System 389
HRT, although not primarily indicated as a treatment for infertility, offers multiple benefits in regulating reproductive hormones,
making it a valuable strategy for enhancing fertility, especially when
individualized to the patient’s specific needs [
86].
6.2 Gene Therapy and RNA-Based Approaches
Nanotechnology, an advanced field of science, holds significant
potential in genetic modification, editing, and repair, particularly
in addressing infertility-related genetic defects. By leveraging the
unique surface properties of nanoparticles, researchers have developed innovative methods to deliver therapeutic agents or genes
into reproductive cells with high precision, thereby enabling targeted gene manipulation. For example, lipid nanoparticle encapsulating CRISPR/Cas9 gene-editing tools were synthesized. This
formulation successfully inhibited cell proliferation and induced
apoptosis in hr-HPV9E/E16-positive cervical cancer SiHa cells
by deactivating the HPV16 oncogene [
87]. Similarly, lipid nano-
particles that encapsulate PLK1-targeting Cas9 mRNA and sgRNA
gene-editing tools were prepared [88]. This breakthrough facilitated the development of a murine model of peritoneal
disseminated ovarian cancer, with nanoparticles administered via
intraperitoneal injection to achieve gene editing at the target site.
Furthermore, broader applications of nanotechnology in
reproduction, including gene editing, repair, imaging, and diagnostics, were explored. Beyond reproduction, this technology has
shown potential in viral infection management [
89]. The
synaptosome-associated 23-kDa protein (SNAP-23), a plasma
membrane protein, plays a crucial role in the transportation of
HIV viral vesicles [
90]. The absence of SNAP-23 in host cells
leads to defective HIV-1 particle synthesis, which could be harnessed as a genetic strategy for preventing HIV transmission. A film
platform using PEGylated poly(D,L-lactic-co-glycolic acid)/polyethylenimine nanoparticles was developed to deliver siRNA targeting dendritic cells, effectively knocking down SNAP-23
91]. These siRNA-loaded nanoparticles, when tested on vaginal
[
epithelial cells in vitro, exhibited efficient release and selective
targeting, offering a promising approach to HIV prevention.
6.3 Personalized Medicine in Reproductive Disorders
Personalized or precision medicine is increasingly applied in reproductive medicine to customize treatments based on an individual’s
unique genetic makeup, health history, and lifestyle factors
This approach has long been integrated into reproductive
92].
[
care, particularly in techniques such as preimplantation genetic
diagnosis (PGD) and preimplantation genetic screening (PGS),
which assess the genetic health of embryos before implantation.
The primary objective of reproductive medicine is to assist infertile
couples in achieving healthy pregnancies, especially for those
affected by genetic disorders. While traditional assisted reproductive technologies (ART) can address infertility issues such as tubal
390 Dhaval J. Kamothi et al.
blockages, they may be inadequate for cases involving genetic
abnormalities. PGD/PGS helps by identifying these genetic issues,
particularly aneuploidy—an abnormal number of chromosomes—
which can affect up to 80% of embryos in women over 41, leading
to IVF failure [
situ hybridization (FISH), which was limited to detecting only a
few chromosomes, to newer methods like array comparative genomic hybridization (array-CGH), single-nucleotide polymorphism
(SNP) microarrays, and next-generation sequencing (NGS), now
allows for a comprehensive examination of all 24 chromosomes.
These advanced techniques significantly improve the accuracy of
identifying aneuploidy and increase pregnancy success rates
[
95]. NGS has emerged as a cost-effective, precise tool, not only
for selecting healthy embryos but also for screening for single-gene
disorders. The integration of technologies like mutated allele
revealed by sequencing with aneuploidy and linkage analyses
(MARSALA), which combines NGS with single-cell genome
amplification, enhances the ability to simultaneously detect aneuploidy, genetic mutations, and mitochondrial abnormalities with
high accuracy [
PGD/PGS process, improving diagnostic precision and success
rates in ART procedures.
implantation (WOI), typically between days 19 and 21 of the
menstrual cycle, during which it becomes receptive to embryo
implantation. This tissue undergoes dynamic structural changes in
response to steroid hormones, creating a favorable environment for
blastocyst attachment [
dow is crucial to prevent reproductive failure due to improper
timing. The endometrial receptivity array (ERA), a genomic diagnostic tool, was developed to determine the precise WOI by analyzing the expression of 238 genes. By comparing a patient’s genetic
profile with reference samples from natural or hormone replacement cycles, the ERA helps identify the optimal timing for embryo
transfer, improving implantation success and pregnancy rates, particularly for those with recurrent implantation failure [
care addresses the complexities of infertility and enhances the efficacy of ART, particularly as the number of individuals experiencing
fertility issues continues to rise. The ability to customize treatment
based on a comprehensive understanding of each patient’s unique
biological characteristics allows for more precise interventions,
leading to improved outcomes in reproductive medicine.
93, 94].
The evolution of screening technologies, from fluorescence in
96]. This advancement has streamlined the
Additionally, the endometrium undergoes a brief window of
97, 98]. Accurate identification of this win-
99, 100].
Thus, the
application of personalized medicine in reproductive
Advances in Drug Delivery to the Reproductive System 391
7 Therapeutic Applications and Innovations
7.1 Infertility and Assisted Reproductive Technologies (ART)
Assisted reproductive technology (ART) comprises a variety of
laboratory methodologies designed to assist couples experiencing
infertility in achieving conception, primarily through procedures
such as in vitro fertilization (IVF) and intracytoplasmic sperm
injection (ICSI). A novel approach to enhance the outcomes of
ART involves the utilization of nanoparticles (NPs) for the targeted
delivery of pharmaceuticals, enzymes, or biomolecules directly into
gametes, which may potentially increase success rates. For example,
mesoporous silica nanoparticles (MSNPs) have been employed in
conjunction with the C105Y peptide, which is designed to selectively target and penetrate the sperm cell membrane without inflicting damage, thereby preserving cellular integrity. Additional
investigations have examined the application of NPs in ART within
agricultural species. In a study conducted in 2020, the administration of gonadotrophin-releasing hormone via chitosan-sodium tripolyphosphate NPs resulted in enhanced bioavailability, even at
merely 25% of the standard dosage [
101]. Furthermore, chitosan-
tripolyphosphate NPs have been employed as carriers for progesterone in cattle, facilitating the regulation of hormonal cycles
through a method known as spray-drying, achieving an encapsulation efficiency ranging from 69% to 75% for progesterone
102]. Additionally, successful loading and delivery of progesterone
[
have been demonstrated using polylactic acid-based NPs [
103] and
polymethylmethacrylate-based NPs as delivery vehicles
[104]. Nanoparticles have also exhibited potential in the preservation of fertility in prepubescent males. The cryopreservation of
immature testicular tissue frequently leads to a significant loss of
spermatogonial cells, which are the sole cells capable of undergoing
spermatogenesis at this developmental stage, thereby considerably
diminishing reproductive potential [
105]. Alginate nanoparticle
matrix was developed encapsulating a necrosis inhibitor factor and
applied it to immature testis tissue derived from a nude mouse
model [
106]. Their findings indicated a significant enhancement
in germ cell integrity and graft survival, presenting promising
opportunities for fertility preservation in human subjects.
7.2 Treatment of Reproductive Cancers
Superparamagnetic iron oxides and aptamer-conjugated gold
nanoparticles, referred to as “nanotheranostic agents specific to
prostate cancer,” have been employed as diagnostic modalities for
prostate cancer. These nanoparticles are designed to encapsulate
the chemotherapeutic agent doxorubicin (DOX) and leverage
image-guided therapy to selectively target malignant prostate
cells. This approach enhances the therapeutic efficacy while mini-
A multitude of studies has validated
mizing systemic toxicity [
107].
the effectiveness of liposomes as drug delivery vehicles for targeting
392 Dhaval J. Kamothi et al.
prostate cancer. One strategy involves the co-encapsulation of
DOX and simvastatin—an established lipid-lowering agent with
anticancer properties—within herceptin-targeted liposomes
[ ], which exhibit a high affinity for HER2 receptors present
108
on prostate tumor cells [ ]. This method has demonstrated a
significant reduction in tumor growth, likely attributable to its antiangiogenic properties, indicating a promising avenue for prostate
cancer therapy [ ]. Furthermore, considering that prostate cancer cells overexpress cyclooxygenase-2 and glucose transporter-1,
both of which are implicated in cancer progression [ ]. One
study proposed a multifunctional liposomal carrier incorporating
celecoxib and genistein [ ]. This combination effectively targets
prostate cancer cells and induces apoptosis. These findings underscore the potential of liposomes as effective drug delivery systems in
the battle against prostate cancer. Paclitaxel, another potent chemotherapeutic agent, targets the cytoskeleton of cancer cells by
stabilizing microtubules within the mitotic spindle, thereby preventing their disassembly and disrupting chromosomal alignment
during metaphase spindle assembly. Paclitaxel was encapsulated
within poly(lactic-co-glycolic acid) nanoparticles and demonstrated
targeted delivery to endometrial cells in a xenograft model, effectively inhibiting tumor growth [ ]. Additionally, various nanoparticles, including bovine serum albumin [ ], gold [ ], and
magnetic iron [ ], have been conjugated with specific ligands
such as folate [ ] and follicle-stimulating hormone receptorbinding peptides to facilitate the delivery of chemotherapeutic
agents to reproductive cancers, including ovarian and uterine cancer. Numerous investigations have explored the application of
nanoparticles as delivery systems for reproductive malignancies.
For example, the encapsulation of the chemotherapeutic agent
epigallocatechin 3-gallate within polysaccharide nanoparticles has
been studied for its potential in treating prostate cancer
[ ]. However, these methodologies necessitate further clinical
118
trials to assess their efficacy in human subjects. Several liposomes
have shown promise in effectively targeting ovarian cells and delivering encapsulated therapeutics. In a murine model, nickelchelating liposomes linked to the recombinant protein ligand
ErbB2 (also known as HER2) successfully targeted metastatic
ovarian tumors that overexpress ErbB2, highlighting their potential
for ovarian cancer treatment [ ]. Subsequent studies have reinforced the feasibility of liposomes in managing ovarian cancer. Cellpenetrating peptides are frequently employed to modify the surfaces of nanoparticles for targeted cellular delivery [ ]. Transferrin receptors, which are often overexpressed in various malignant
cells, including those of ovarian cancer, serve as effective targets
[ ]. In this context, liposomes were developed that were double-
121
conjugated with the tumor-targeting, arginine-rich cellpenetrating peptide octa-arginine (R8) and transferrin to
109
110
111
112
113
115114
116
117
119
120
Advances in Drug Delivery to the Reproductive System 393
specifically target A2780 ovarian cancer cells [122]. These liposomes, loaded with DOX, achieved selective targeting of malignant
cells and facilitated successful intracellular dr ug delivery. A correlation has been established between the expression levels of the
CD44 cell membrane receptor and cancer progression, including
ovarian cancer. In this regard, PEG-paclitaxel was loaded onto antiCD44 antibody-decorated liposomes, effectively inhibiting the
proliferation of CD44-positive ovarian cancer cell
over,
the conjugation of liposomes with plectin—an abundant
s [
123]. More-
cytolinker expressed on the surface of ovarian cells during the
transition from healthy to malignant tissue—enhanced the selective
targeting of these cancer cells [
124]. When poly(ADP-ribose) poly-
merase inhibitors, which are effective against BRCA1/2-expressing
ovarian cancer cells [
125], were loaded onto these modified lipo-
somes, they successfully targeted ovarian cancer cells and resulted in
a substantial reduction in tumor size in a murine model.
7.3 Infections and
Inflammatory
Conditions
Highly active antiretroviral therapy (HAART) serves as a crucial
intervention for managing HIV infection; however, it necessitates
lifelong adherence to medication, as HAART is unable to
completely eradicate the virus from the host’s system. In response
to this limitation, researchers have created a nanoparticle-based
strategy known as laser antiretroviral therapy, which facilitates the
prolonged and controlled release of antiretroviral agents. This
techniq
employs nanoparticles (NPs) to maintain the release of
ue
lamivudine, a nucleoside reverse transcriptase inhibitor, thereby
ensuring therapeutic efficacy for up to 30 days following a single
126].
administration [
Furthermore, NPs have been explored for
their potential in addressing various genital infections beyond HIV,
with certain vaginal gels designed to mitigate the risk of viral
infections such as human papillomavirus and herpes simplex vir us.
These gels operate on the premise that specific poly-anionic and
peptide dendrimer NPs can competitively inhibit the binding of
these pathogens to cellular receptors, thereby lowering the likelihood of infection [
127].
Additionally, dendrimers have been investigated as delivery vehicles for azithromycin in the treatment of
Chlamydia trachomatis infections. Ongoing research has also
examined the application of NPs in the development of vaccines
against Chlamydia [
129], and the management of vaginal candidiasis [130].
[
128], the prevention of herpes simplex virus
Nevertheless, further investigations are warranted to evaluate the efficacy of
NPs for these applications. Several liposomal formulations have
achieved clinical approval and are currently utilized as drug delivery
systems for various reproductive system malignancies, including
ovarian cancer, breast cancer, and AIDS-related Kaposi’s sarcoma.
Notably, DOX-loaded PEGylated liposomes were the first to demonstrate clinical success in oncological therapy, enhancing the
drug’s ability to evade immune detection while prolonging its
394 Dhaval J. Kamothi et al.
systemic circulation and allowing for a reduced dosage of doxorubicin (DOX). This delivery method consequently mitigates the
systemic adverse effects commonly associated with DOX administration [
cle remains the inability of current therapies to completely eliminate
the virus from reservoir sites within the body, leading to persistent
release of viral DNA into the bloodstream [
potent antiviral agent employed in the treatment of HIV-1, functions by inhibiting viral DNA synthesis; however, its short half-life
of 0.8–1.5 h necessitate frequent dosing, which can result in severe
side effects such as neuropathy and lactic acidosis, thereby limiting
its clinical application [
encapsulating stavudine within
targeting HIV reservoir sites [
significantly reduced dosage of the antiviral agent while facilitating
a linear and sustained release over a 12-h period, effectively reaching all reservoir sites. This innovative method has demonstrated a
reduction in circulating viremia while concurrently decreasing the
systemic complications associated with stavudine treatment.
aberrant growth of tissue that resembles the endometrial lining
outside the uterine cavity, leading to considerable physical and
psychological distress among women of reproductive age. Current
therapeutic approaches primarily aim to alleviate symptoms
through surgical intervention and hormonal treatments
[
135]. Nevertheless, recent investigations have examined the
potential application of nanoparticles (NPs) in the management
of endometriosis. Two distinct studies have indicated that NPs
may serve as effective vehicles for drug delivery to mitigate the
condition. In one investigation, it was reported that the administration of chitosan nanoparticles encapsulating gene therapy in a rat
model resulted in a reduction of endometrial lesion size and inhibited cyst formation [
lipid nanoparticles, which exhibit structural similarities to human
low-density lipoproteins (LDL), were effectively internalized by
endometrial tissues [
promising avenue for targeted drug delivery to the affected regions,
potentially providing an alternative to conventional surgical
methods.
131]. In the context of HIV treatment, a significant obsta-
132]. Stavudine, a
133]. A novel approach was proposed
gelatin nanoliposomes specifically
134]. This strategy allows for a
Endometriosis is a debilitating condition characterized by the
136]. In a separate study, it was illustrated that
137]. These lipid nanoparticles present a
7.4 Contraceptive Technologies
Nanomaterials present considerable promise for localized contraceptive applications, including the modulation of the vaginal
environment and the establishment of localized acidic conditions
conducive to contraception. Previous research has demonstrated
the efficacy of a PEVA-PLA hybrid hydrogel system in conjunction
with polar tenofovir [
36]. By varying the ratio of PLA to PEVA,
researchers were able to achieve a prolonged, slow-release profile,
indicating its potential utility in contraception, pregnancy
Advances in Drug Delivery to the Reproductive System 395
prevention, and even the mitigation of HIV transmission. Biodegradable nanoparticles were developed composed of poly(lactic
acid) utilizing a single emulsion technique, resulting in an average
particle size of 75 nm [
cavity
murine models, these nanoparticles migrated retrograde
of
138
pon introduction into the vaginal
]. U
through the cervix and accumulated in the uterus. Subsequent
analysis of uterine samples indicated the activation of
pro-inflammatory signals, such as RANTES and TNF, thereby
creating an environment that inhibited successful pregnancy. Nanomaterials are advantageous for impeding sperm motility, representing a promising avenue for contraceptive strategie
surface
morphology or chemical properties of nanoparticles, it is
s. By altering the
feasible to obstruct sperm binding and penetration of the oocyte,
thus achieving contraceptive efficacy [
mechanism of
involve the release of Cu
copper intrauterine devices (IUDs) is believed to
2+
ions, which incapacitate sperm and
139]. The contraceptive
diminish myometrial contractions. Investigation was carried out
for the application of nano-Cu/LDPE as a delivery system for
copper in intrauterine devices [
140]. Copper nanoparticles were
incorporated into LDPE through various physical and chemical
methods, resulting in a composite material with a uniform distribution of nanoparticles. By modulating the spatial arrangement
between the copper nanoparticles and LDPE, they were able to
control the exposure to the corrosive medium (Cu
2+
ions), facilitating a rapid and consistent release rate within a 5-h timeframe
[
141]. The application of nanomaterials in contraceptive monitor-
an expanding area of research, presenting novel opportunities
ing is
for enhanced fertility tracking. Nanoparticles can be utilized to
label specific physiological markers, enabling real-time monitoring
of fertility indicators. For example, nanomaterials can be employed
to label biomarkers such as FSH and LH [142, 143] to track
ovulation cycles, thereby providing precise data on a woman’s
fertility status and aiding in the selection of appropriate contraceptive methods or fertility planning approaches. Furthermore, nanoparticle sensors can be employed to monitor hormone levels,
including estrogen and progesterone, which assists in evaluating
fertility, menstrual cycles, and hormonal imbalances
[
144, 145]. Additionally
, nanotechnology can be leveraged for
male contraception, where nanoparticles function as delivery systems for contraceptive pharmaceuticals or spermicide agents within
the male reproductive tract, thereby enabling controlled contraceptive outcomes.
8 Safety and Regulatory Considerations
The advancement of novel drug delivery systems (NDDS) has
significantly transformed reproductive medicine by improving
396 Dhaval J. Kamothi et al.
drug targeting, reducing systemic side effects, and enhancing therapeutic outcomes. Various NDDS types have been developed,
including nanoparticle-based systems, hydrogels, microneedles,
and implants or intrauterine devices [
employed
delivery to reproductive tumors, and hormone replacement treatments. However, like all emerging technologies, they present safety
concerns that warrant careful consideration. Key issues include
biocompatibility, targeting precision, and potential long-term
adverse effects, particularly when applied to sensitive reproductive
tissues such as the ovaries, uterus, or test
used in NDDS
complications like necrosis, inflammation, or reproductive
dysfunctions.
or hormone analogs may disrupt endocrine function, and prolonged exposure to synthetic hormones could lead to long-term
reproductive health complications [
needles can result in localized tissue damage or scarring, potentially
affecting reproductive organs or functions. Hydrogels, if improperly formulated, may cause mucosal damage or infections after
repeated use [
delivery can lead to unintended effects on non-reproductive
organs, causing systemic hormonal imbalances or damage to the
liver or kidneys. In contraceptive applications, mistargeting could
result in incomplete suppression of ovulation or sperm production,
potentially leading to unintended pregnancies. For cancer treatments, off-target effects might impair fertility by damaging nearby
healthy reproductive tissues [
also a concern with some NDDS, especially when drugs are delivered via nanoparticles or implants, as they may irreversibly harm the
ovaries or testes. Furthermore, certain materials or agents used in
these systems may pose carcinogenic risks, particularly in reproductive tissues with high cellular turnover [
efforts to develop more biocompatible, biodegradable materials for
NDDS aim to mitigate these risks and minimize toxicity, tissue
damage, and long-term complications. Tailoring NDDS to individual genetic, hormonal, and reproductive profiles could optimize
treatment and reduce side effects [
tion (FDA), the European Medicines Agency (EMA), and the
World Health Organization (WHO), are tasked with assessing the
safety and efficacy of novel drugs and drug delivery systems
[
153]. In the USA, the FDA oversees the regulatory process,
ensuring that stringent preclinical and clinical testing is conducted
before new drug delivery technologies reach the market. Similarly,
the EMA evaluates medicinal products in Europe to ensure
controlled
for
146
contraceptive release, targeted therapy
hese systems are
]. T
147]. The materials
es [
must be compatible with these tissues to avoid
Additionally, some delivery systems that administer hormones
148]. Improper use of micro-
149].
Although N
DDS a
re designed to target specific areas, errors in
150]
ong-term fertility impacts are
. L
151]. However, ongoing
.
152]
Regulatory
bodies, such as the US Food and Drug Administra-
Advances in Drug Delivery to the Reproductive System 397
compliance with safety and efficacy standards. In low- and middleincome countries, WHO provides guidelines to ensure the safety of
drug delivery technologies [
Given the relative novelty of many NDDS, there is limited
long-term data on their effects, especially on reproductive health,
which necessitates thorough testing by regulatory agencies. The
application of NDDS in fertility treatments or contraception also
raises ethical considerations, particularly regarding potential longterm reproductive consequences and the manipulation of reproductive health for non-therapeutic purposes. Therefore, regulatory
guidelines must ensure that clinical trial participants are fully
informed of the risks and benefits associated with these new
technologies.
9 Future Directions and Emerging Trends
Advancements in artificial intelligence (AI) and machine lear ning
(ML) are revolutionizing various sectors, including healthcare and
pharmaceuticals, by enabling researchers and clinicians to develop
more precise, efficient, and personalized drug delivery systems.
One significant application of these technologies is in the design
of reproductive drug delivery systems [
delivery presents unique challenges due to the complex physiological processes involved, including those related to fertility, contraception, hormone regulation, and reproductive disorders.
Traditional reproductive drug delivery methods often face limitations in ensuring consistent drug release and bioavailability
156]. AI and ML offer significant benefits by optimizing drug
[
delivery parameters, predicting patient-specific responses, and
enhancing the overall effectiveness of reproductive therapies. Techniques such as predictive modeling, drug-target matching, and
formulation optimization improve the performance and design of
reproductive drug delivery systems [
159].
earn
ing, in particular, has been instrumental in
of biotechnology and reproductive medicine are
Machine l
advancing research and clinical aspects of drug design. ML algorithms can analyze vast datasets to uncover patterns and correlations, enabling the simulation of drug release kinetics and
absorption in specific tissues [
the development of nanotechnology-based drug delivery systems.
Nanoparticles and nanocarriers, which enhance bioavailability and
tissue targeting, are increasingly used in reproductive drug delivery.
ML also facilitates virtual clinical trials, reducing the time and cost
of bringing new reproductive drugs and delivery systems to the
market [
The fields
advancing rapidly, intersecting in key areas such as fertility treatments, genetic engineering, hormone therapy, and regenerative
154].
155]. Reproductive drug
157].
158]. Moreover, ML is central to
398 Dhaval J. Kamothi et al.
medicine. The integration of emerging biotechnologies is poised to
transform reproductive healthcare, providing innovative solutions
for challenges such as infertility, genetic disorders, and age-related
reproductive decline [
ments, gene editing, stem cell therapies, and artificial gametes. As
the understanding of genetics and molecular biology deepens,
fertility treatments are increasingly personalized, with advances in
genetic screening and AI-powered algorithms allowing for customized treatment plans based on individual genetic profiles
[
160]
ing
(IVF) [
prehensive genetic profiling, allowing for the detection of inherited
conditions and traits that influence fertility. Pharmacogenomics will
play a pivotal role in personalizing drug regimens in fertility treatments, optimizing medications for hormonal therapies and ovarian
stimulants according to a patient’s genetic profile. This precision
reduces side effects and improves treatment efficacy [
editing technologies, such as CRISPR-Cas9, offer the potential to
correct genetic causes of infertility and prevent the transmission of
hereditary diseases through assisted reproductive technologies
(ART) [
icine are opening new possibilities for treating infertility. One of the
most promising developments is the generation of artificial gametes
from stem cells, which could benefit individuals unable to produce
viable gametes due to conditions like premature ovarian failure or
azoospermia [
preservation and treatment options [
sitates interdisciplinary collaboration. The complexity of reproductive medicine, which involves processes such as hormonal
regulation and tissue-specific targeting, requires expertise from
diverse fields including pharmacology, biotechnology, chemistry,
material science, engineering, and artificial intelligence. These multidisciplinary efforts enhance the precision, safety, and accessibility
of reproductive treatments, ultimately improving global reproductive health outcomes.
12]. This includes personalized fertility treat-
. Preimplantation genetic testing (PGT) enables the screen-
of
embr
yos
for
genetic
disorders
during
in
vitro
fer
tilization
161].
Future biotechnological advancements will enable more com-
162]. Gene
163]. Additionally, stem cell therapy and regenerative med-
164]. This breakthrough could revolutionize fertility
165].
The advancement of reproductive drug delivery systems neces-
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