RARE DISEASE
Rare female infertility
Rare female infertility
Rare female infertility
Drug discovery
1
drug
With orphan designation
Overview
Rare female infertility encompasses conditions such as congenital uterine anomalies (e.g., septate uterus), premature ovarian insufficiency, severe endometriosis, and genetic disorders (e.g., Turner syndrome). These etiologies often require specialized diagnostic approaches, including imaging and genetic testing, and may involve advanced assisted reproductive technologies (ART) or surgical interventions for management [4][5][11][16].
Population
Affects ~16.2% of women with uterine abnormalities (polyps, fibroids, adhesions) and 10–15% with tubal disorders linked to untreated infections or endometriosis [4][5][14].
Premature ovarian insufficiency impacts 1% of women under 40, while severe endometriosis affects ~30–50% of infertile women [9][16].
Burden
Psychological distress, social stigma, and financial strain due to high treatment costs (e.g., IVF cycle costs $12,000–$25,000) [12][16][18].
Delayed diagnosis (e.g., endometriosis: 7–8 years average delay) exacerbates complications like chronic pain and reduced quality of life [16][20].
Disproportionate access barriers in low-resource settings, where <30% of countries prioritize fertility care [4][10].
Categories: rare infertility disorders
Research Papers
298 drug discovery papers about Rare female infertility, with 3 first-in-class and 1 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
298 drug discovery papers about Rare female infertility, with 3 first-in-class and 1 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2026-07-31 | Utility of homoeopathic medicines in management of cases of PCOS - A retrospective hospital based study
Introduction: This comprehensive study evaluates the effectiveness of Homoeopathic medicines in the management of PCOS cases through a hospital based retrospective study & identifies frequently used Homoeopathic medicines and the prominent miasm in the reported outcomes. PCOS is a multisystem disorder on the rise in the last few years. It is marked by irregular menses, Hyperandrogenism, hirsutism, acne, infertility with global prevalence of 6% to 26%.Homoeopathy is a holistic system, which helps in this endocrine disorder. Aim:To identify utility of homoeopathic medicines,the predominant miasm in cases of PCOS/PCOD through retrospective hospital based study. Materials and methods: It includes analysis of 792 female patients treated in the last 3 years (January 2021 - January 2024) of reproductive age (12 to 50 years) from a Govt. homoeo Medical College & Hospital, Rajamahendravaram, India. The data collected in specifically designed formats the master charts and details shown in the form of Tables and charts. Results: Most patients presented with irregular menses, dysmenorrhea, acne, weight gain, hirsutism, and infertility. Individualized homoeopathic medicines, mainly polycrests were frequently used with positive outcomes including menstrual regularization in over 60% of cases. Antimiasmatics and rare remedies were also applied. The predominant miasm identified through retrospective study was psoro-sycotic. Conclusion: This retrospective study data indicates individualized/constitutional homoeopathic medicines like polycrests playing a significant role in managing PCOS symptoms, particularly menstrual irregularities and infertility. The predominant miasm identified is Psorosycotic, antimiasmatics complement treatment success. It shows that polycrests are proven effective in treating PCOS. There is a requirement for well documented case formats in hospital settings, well planned, pragmatic research studies and RCTs.
2026-07-31 | Therapeutic Roles and Safety Profiles of Non-Vitamin Antioxidant Supplements in Female Infertility: A Narrative Review.
Treatment of female infertility consists different strategies including metabolic, hormonal and surgical therapeutic modalities. Non-vitamin supplements with antioxidant activity as carnitines, Inositols, Poly Unsaturated Fatty Acids (PUFAs), coenzyme Q10 and melatonin are among those with most popularity, but their prescription may confer some warnings. This review narrates the antioxidant mechanism of these supplements, beside their effect on outcomes of infertility treatment while considering side effects, warnings and ranges of doses. Carnitines are used for energy production and fat metabolism, while they have anti-aging and antioxidant effects. Supplementation with carnitines improve obesity outcomes, especially in Poly Cystic Ovarian Disease (PCOS) patients. Rare cases have shown increasing risk of seizure with levocarnitine. Coenzyme Q10 (Ubiquinone) has shown benefit in patients with PCOS or poor ovarian responders. It significantly increased live birth rate and the side effects are minimal even in higher doses. Poly Unsaturated Fatty Acids (PUFAs) have shown impact on follicular development and embryo quality. The hazard is increasing lipid low density lipoprotein (LDL) in high doses. Use of inositols in female infertility treatment is due to its metabolic effect and insulin resistance in PCOS patients resulting in decreasing use of gonadotropins. They have produced acceptable results about count of follicles and oocyte quality. Hypoglycemic effects of inositols have been reported as side effect, especially in combination with other hypoglycemic agents. Melatonin can increase the clinical pregnancy rate, and improve the outcomes about oocyte and quality of embryo via receptor- and non-receptor- action. Dizziness, drowsiness, and headache are reported in higher doses of melatonin. The attitude that all supplement can be prescribed without restriction endangers susceptible patients. Hence, increasing our knowledge about efficacy and safety profile can help individualize prescription of supplements for female infertility.
2026-07-30 | Hemoperitoneum after oocyte retrieval in women undergoing ART: A 2017-2022 retrospective cohort study with a historical comparison to 1996-2016.
To estimate the incidence and predictors of severity-defined hemoperitoneum after oocyte retrieval in a contemporary 2017-2022 cohort, and to place these findings in context with the center's previously published 1996-2016 experience. Retrospective cohort study including all 13,192 oocyte retrieval procedures performed at a single fertility center from January 2017 to December 2022 in 9,346 women. The primary endpoint was documented hemoperitoneum associated with hemoglobin decrease ≥ 2 g/dL and/or hospital admission, surgery or blood transfusion. The 1996-2016 cohort was retained only as an aggregate historical comparator. Predictors were estimated with robust Poisson regression clustered by patient identifier. Severity-defined hemoperitoneum was identified among 50 retrievals (0.379 %), including 46 cases with hemoglobin decrease ≥ 2 g/dL, 44 admissions, 20 surgical procedures and 12 transfusions. The contemporary primary endpoint was recorded more frequently than the historical aggregate hemorrhagic comparator (RR 1.67, 95 % CI 1.14-2.46, p = 0.010), whereas surgery did not differ significantly (RR 1.81, 95 % CI 0.97-3.36, p = 0.069). In the primary contemporary model, lower BMI (RR 0.80 per kg/m2, 95 % CI 0.73-0.88, p < 0.001), higher AMH (RR 1.08, 95 % CI 1.02-1.14, p = 0.010) and longer total retrieval time (RR 1.03 per minute, 95 % CI 1.00-1.06, p = 0.044) were associated with severity-defined hemoperitoneum. Hemoperitoneum after oocyte retrieval was rare, but associated with substantial morbidity when it occurred. Lower BMI and higher AMH were the main patient-level risk markers. Total retrieval time remained modestly associated with the risk, and should be interpreted as a marker of ovarian response and procedural complexity. The higher rate observed in the contemporary cohort should be interpreted cautiously, as surgery did not increase significantly. NCT05895227, May 31st, 2023.
2026-06-29 | Clinical pregnancy outcomes with assisted reproduction in patients with 17α-Hydroxylase/17, 20-lyase deficiency: a single center cohort study and integrated analysis with reported cases
Background 17α-hydroxylase/17, 20-lyase deficiency (17OHD) represents a rare form of congenital adrenal hyperplasia. Affected 46, XX females typically present with sexual development abnormalities, endocrine disturbances and infertility. While assisted reproductive technology (ART) enables pregnancies in these patients, our knowledge about optimal management strategies and pregnancy outcomes remains limited. Methods We conducted a retrospective cohort study of women with 17OHD who achieved clinical pregnancy at our center between January 2009 and August 2025, followed until December 2025. Moreover, we performed a systematic review of published cases, extracting and analyzing demographic, clinical, laboratory, treatment, and outcome data. Results Among 20 female patients with 17OHD at our center, six desired fertility and three achieved clinical pregnancy with ART. Combined with 17 reported cases from 12 studies, a total of 20 pregnancies resulted in 23 live births. Median age at pregnancy preparation was 29 (range 21–42) years. The prevalence rates of hypertension and adrenal insufficiency were 25.0% (5/20) and 50.0% (10/20), respectively. Median follicular-phase progesterone was 20.8 nmol/L. Seventeen women conceived via frozen embryo transfer (FET) following ovarian stimulation, including nine with GnRH agonists (GnRHa), six with progestin-primed ovarian stimulation, one with GnRH antagonists, and one with GnRHa short protocol, respectively. Nearly 95% (18/19) participants received glucocorticoids before embryo transfer. Pregnancy complications (including gestational hypertension, diabetes, preeclampsia, and HELLP syndrome) occurred in 46.2% (6/13) cases. Only 25% (5/20) of the participants had term vaginal deliveries. All five offspring that were followed up developed normally. Conclusions For women with 17OHD, a treatment protocol combining glucocorticoid-assisted progesterone suppression with FET represents a viable strategy to achieve pregnancy. However, such patients face high risks of adverse maternal and perinatal outcomes, requiring multidisciplinary management throughout gestation.
2026-04-01 | Comment on “Farnesylation-Dependent Kinetochore Targeting of Centromere Protein F Is Essential for Oocyte Meiotic Progression and Female Fertility”
Successful cell division during meiosis is dependent on accurate chromosome segregation; the role of centromeres, kinetochores, and spindle microtubules is well characterized in mitosis, but the role of certain proteins surrounding them remains uncertain in meiosis. This is important to understand because the arrest of maturation of oocytes is a common origin of female infertility, but the mechanisms for this are largely unknown. This study was designed to assess the regulatory mechanism of the farnesylation of centromere protein F on its meiotic function as well as evaluate any association between mutations in centromere protein F and female oocyte maturation disorders. This study used oocyte microinjection, western blotting, co-immunoprecipitation, and immunofluorescence to characterize the role of centromere protein F. During mitosis, this protein assists in chromosome segregation, but it is currently unknown if its role remains the same during meiosis. This study used a mouse model to explore both genetic and pharmacologic methods of farnesylation, and to verify the mechanism of mutations in oocyte maturation. Microinjection of centromere protein F siRNA reduced maturation rates significantly, with many halting maturation at metaphase I ( P <0.05). Farnesylation likewise reduced the rate of oocyte maturation ( P <0.01), and additionally weakened the interationc between centromere protein F and Aurora kinase B, which was confirmed by co-immunoprecipitation ( P <0.01). Farnesylation also disrupted kinetochore localization, contributing to the arrest of oocyte maturation. Immunofluorescence analysis further showed that centromere protein F localized at kinetochores by metaphase I, causing arrested development. Screening human patients with infertility resulted in the identification of 4 individuals with rare heterozygous variants in the CENP-F gene that were associated with the arrest of oocyte maturation. When testing centromere protein F derived from patients who were identified to have a genetic mutation in this protein, microinjection of the patient-derived centromere protein F also caused significantly reduced maturation in mouse oocytes ( P <0.01). Two identified mutations reduced the fanesylation of centromere protein F as well as disrupted kinetochore localization and damaged the Aurora kinase B interaction. These results indicate that there is a direct association between centromere protein F mutations and infertility, specifically the arrest of oocyte maturation during meiosis. These findings contribute evidence to the controversy surrounding the influence of farnesylation on the localization of CENP- F, with some previous studies showing no effect of farneslyation and others showing a direct interaction between molecules that is dependent on farneslyation. This study emphasizes the need for further clinical research to validate the pathology of these mutations in diverse populations. Future studies should also attempt to ethically validate the results of these mouse models in human models and examine other possible mechanisms for arrested maturation of oocytes such as disruption of microtubule binding. (Summarized from Zhong O, Wang C, Zhang J, et al. Farnesylation-dependent kinetochore targeting of centromere protein F is essential for oocyte meiotic progression and female fertility. Am J Obstet Gynecol. 2026;234:116-140. doi: 10.1016/j.ajog.2025.08.031)
2026-07-31 | Utility of homoeopathic medicines in management of cases of PCOS - A retrospective hospital based study
Introduction: This comprehensive study evaluates the effectiveness of Homoeopathic medicines in the management of PCOS cases through a hospital based retrospective study & identifies frequently used Homoeopathic medicines and the prominent miasm in the reported outcomes. PCOS is a multisystem disorder on the rise in the last few years. It is marked by irregular menses, Hyperandrogenism, hirsutism, acne, infertility with global prevalence of 6% to 26%.Homoeopathy is a holistic system, which helps in this endocrine disorder. Aim:To identify utility of homoeopathic medicines,the predominant miasm in cases of PCOS/PCOD through retrospective hospital based study. Materials and methods: It includes analysis of 792 female patients treated in the last 3 years (January 2021 - January 2024) of reproductive age (12 to 50 years) from a Govt. homoeo Medical College & Hospital, Rajamahendravaram, India. The data collected in specifically designed formats the master charts and details shown in the form of Tables and charts. Results: Most patients presented with irregular menses, dysmenorrhea, acne, weight gain, hirsutism, and infertility. Individualized homoeopathic medicines, mainly polycrests were frequently used with positive outcomes including menstrual regularization in over 60% of cases. Antimiasmatics and rare remedies were also applied. The predominant miasm identified through retrospective study was psoro-sycotic. Conclusion: This retrospective study data indicates individualized/constitutional homoeopathic medicines like polycrests playing a significant role in managing PCOS symptoms, particularly menstrual irregularities and infertility. The predominant miasm identified is Psorosycotic, antimiasmatics complement treatment success. It shows that polycrests are proven effective in treating PCOS. There is a requirement for well documented case formats in hospital settings, well planned, pragmatic research studies and RCTs.
2026-07-31 | Therapeutic Roles and Safety Profiles of Non-Vitamin Antioxidant Supplements in Female Infertility: A Narrative Review.
Treatment of female infertility consists different strategies including metabolic, hormonal and surgical therapeutic modalities. Non-vitamin supplements with antioxidant activity as carnitines, Inositols, Poly Unsaturated Fatty Acids (PUFAs), coenzyme Q10 and melatonin are among those with most popularity, but their prescription may confer some warnings. This review narrates the antioxidant mechanism of these supplements, beside their effect on outcomes of infertility treatment while considering side effects, warnings and ranges of doses. Carnitines are used for energy production and fat metabolism, while they have anti-aging and antioxidant effects. Supplementation with carnitines improve obesity outcomes, especially in Poly Cystic Ovarian Disease (PCOS) patients. Rare cases have shown increasing risk of seizure with levocarnitine. Coenzyme Q10 (Ubiquinone) has shown benefit in patients with PCOS or poor ovarian responders. It significantly increased live birth rate and the side effects are minimal even in higher doses. Poly Unsaturated Fatty Acids (PUFAs) have shown impact on follicular development and embryo quality. The hazard is increasing lipid low density lipoprotein (LDL) in high doses. Use of inositols in female infertility treatment is due to its metabolic effect and insulin resistance in PCOS patients resulting in decreasing use of gonadotropins. They have produced acceptable results about count of follicles and oocyte quality. Hypoglycemic effects of inositols have been reported as side effect, especially in combination with other hypoglycemic agents. Melatonin can increase the clinical pregnancy rate, and improve the outcomes about oocyte and quality of embryo via receptor- and non-receptor- action. Dizziness, drowsiness, and headache are reported in higher doses of melatonin. The attitude that all supplement can be prescribed without restriction endangers susceptible patients. Hence, increasing our knowledge about efficacy and safety profile can help individualize prescription of supplements for female infertility.
2026-07-30 | Hemoperitoneum after oocyte retrieval in women undergoing ART: A 2017-2022 retrospective cohort study with a historical comparison to 1996-2016.
To estimate the incidence and predictors of severity-defined hemoperitoneum after oocyte retrieval in a contemporary 2017-2022 cohort, and to place these findings in context with the center's previously published 1996-2016 experience. Retrospective cohort study including all 13,192 oocyte retrieval procedures performed at a single fertility center from January 2017 to December 2022 in 9,346 women. The primary endpoint was documented hemoperitoneum associated with hemoglobin decrease ≥ 2 g/dL and/or hospital admission, surgery or blood transfusion. The 1996-2016 cohort was retained only as an aggregate historical comparator. Predictors were estimated with robust Poisson regression clustered by patient identifier. Severity-defined hemoperitoneum was identified among 50 retrievals (0.379 %), including 46 cases with hemoglobin decrease ≥ 2 g/dL, 44 admissions, 20 surgical procedures and 12 transfusions. The contemporary primary endpoint was recorded more frequently than the historical aggregate hemorrhagic comparator (RR 1.67, 95 % CI 1.14-2.46, p = 0.010), whereas surgery did not differ significantly (RR 1.81, 95 % CI 0.97-3.36, p = 0.069). In the primary contemporary model, lower BMI (RR 0.80 per kg/m2, 95 % CI 0.73-0.88, p < 0.001), higher AMH (RR 1.08, 95 % CI 1.02-1.14, p = 0.010) and longer total retrieval time (RR 1.03 per minute, 95 % CI 1.00-1.06, p = 0.044) were associated with severity-defined hemoperitoneum. Hemoperitoneum after oocyte retrieval was rare, but associated with substantial morbidity when it occurred. Lower BMI and higher AMH were the main patient-level risk markers. Total retrieval time remained modestly associated with the risk, and should be interpreted as a marker of ovarian response and procedural complexity. The higher rate observed in the contemporary cohort should be interpreted cautiously, as surgery did not increase significantly. NCT05895227, May 31st, 2023.
2026-06-29 | Clinical pregnancy outcomes with assisted reproduction in patients with 17α-Hydroxylase/17, 20-lyase deficiency: a single center cohort study and integrated analysis with reported cases
Background 17α-hydroxylase/17, 20-lyase deficiency (17OHD) represents a rare form of congenital adrenal hyperplasia. Affected 46, XX females typically present with sexual development abnormalities, endocrine disturbances and infertility. While assisted reproductive technology (ART) enables pregnancies in these patients, our knowledge about optimal management strategies and pregnancy outcomes remains limited. Methods We conducted a retrospective cohort study of women with 17OHD who achieved clinical pregnancy at our center between January 2009 and August 2025, followed until December 2025. Moreover, we performed a systematic review of published cases, extracting and analyzing demographic, clinical, laboratory, treatment, and outcome data. Results Among 20 female patients with 17OHD at our center, six desired fertility and three achieved clinical pregnancy with ART. Combined with 17 reported cases from 12 studies, a total of 20 pregnancies resulted in 23 live births. Median age at pregnancy preparation was 29 (range 21–42) years. The prevalence rates of hypertension and adrenal insufficiency were 25.0% (5/20) and 50.0% (10/20), respectively. Median follicular-phase progesterone was 20.8 nmol/L. Seventeen women conceived via frozen embryo transfer (FET) following ovarian stimulation, including nine with GnRH agonists (GnRHa), six with progestin-primed ovarian stimulation, one with GnRH antagonists, and one with GnRHa short protocol, respectively. Nearly 95% (18/19) participants received glucocorticoids before embryo transfer. Pregnancy complications (including gestational hypertension, diabetes, preeclampsia, and HELLP syndrome) occurred in 46.2% (6/13) cases. Only 25% (5/20) of the participants had term vaginal deliveries. All five offspring that were followed up developed normally. Conclusions For women with 17OHD, a treatment protocol combining glucocorticoid-assisted progesterone suppression with FET represents a viable strategy to achieve pregnancy. However, such patients face high risks of adverse maternal and perinatal outcomes, requiring multidisciplinary management throughout gestation.
2026-04-01 | Comment on “Farnesylation-Dependent Kinetochore Targeting of Centromere Protein F Is Essential for Oocyte Meiotic Progression and Female Fertility”
Successful cell division during meiosis is dependent on accurate chromosome segregation; the role of centromeres, kinetochores, and spindle microtubules is well characterized in mitosis, but the role of certain proteins surrounding them remains uncertain in meiosis. This is important to understand because the arrest of maturation of oocytes is a common origin of female infertility, but the mechanisms for this are largely unknown. This study was designed to assess the regulatory mechanism of the farnesylation of centromere protein F on its meiotic function as well as evaluate any association between mutations in centromere protein F and female oocyte maturation disorders. This study used oocyte microinjection, western blotting, co-immunoprecipitation, and immunofluorescence to characterize the role of centromere protein F. During mitosis, this protein assists in chromosome segregation, but it is currently unknown if its role remains the same during meiosis. This study used a mouse model to explore both genetic and pharmacologic methods of farnesylation, and to verify the mechanism of mutations in oocyte maturation. Microinjection of centromere protein F siRNA reduced maturation rates significantly, with many halting maturation at metaphase I ( P <0.05). Farnesylation likewise reduced the rate of oocyte maturation ( P <0.01), and additionally weakened the interationc between centromere protein F and Aurora kinase B, which was confirmed by co-immunoprecipitation ( P <0.01). Farnesylation also disrupted kinetochore localization, contributing to the arrest of oocyte maturation. Immunofluorescence analysis further showed that centromere protein F localized at kinetochores by metaphase I, causing arrested development. Screening human patients with infertility resulted in the identification of 4 individuals with rare heterozygous variants in the CENP-F gene that were associated with the arrest of oocyte maturation. When testing centromere protein F derived from patients who were identified to have a genetic mutation in this protein, microinjection of the patient-derived centromere protein F also caused significantly reduced maturation in mouse oocytes ( P <0.01). Two identified mutations reduced the fanesylation of centromere protein F as well as disrupted kinetochore localization and damaged the Aurora kinase B interaction. These results indicate that there is a direct association between centromere protein F mutations and infertility, specifically the arrest of oocyte maturation during meiosis. These findings contribute evidence to the controversy surrounding the influence of farnesylation on the localization of CENP- F, with some previous studies showing no effect of farneslyation and others showing a direct interaction between molecules that is dependent on farneslyation. This study emphasizes the need for further clinical research to validate the pathology of these mutations in diverse populations. Future studies should also attempt to ethically validate the results of these mouse models in human models and examine other possible mechanisms for arrested maturation of oocytes such as disruption of microtubule binding. (Summarized from Zhong O, Wang C, Zhang J, et al. Farnesylation-dependent kinetochore targeting of centromere protein F is essential for oocyte meiotic progression and female fertility. Am J Obstet Gynecol. 2026;234:116-140. doi: 10.1016/j.ajog.2025.08.031)
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Drug Discovery Landscape
1 orphan drug designation for Rare female infertility.
1 orphan drug designation for Rare female infertility.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
autologous adult bone marrow-derived and unexpanded CD133+ hematopoietic stem cells (CD133+ BMDSCs) mobilized from peripheral blood (PB) | cell therapies | FDA | 2019-02-01 | — | Asherman Therapy S.L.U. |
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