MedGen

Blepharophimosis, ptosis, and epicanthus inversus syndrome (BPES) is defined by a complex eyelid malformation characterized by four major features, all present at birth: blepharophimosis, ptosis, epicanthus inversus, and telecanthus. BPES type I includes the four major features and primary ovarian insufficiency; BPES type II includes only the four major features. Other ophthalmic manifestations that can be associated with BPES include dysplastic eyelids, lacrimal duct anomalies, strabismus, refractive errors, and amblyopia. Other craniofacial features may include a broad nasal bridge and low-set ears. [from GeneReviews]

Oocyte/zygote/embryo maturation arrest-5 (OZEMA5) is characterized by female infertility due to inability of the oocyte to exit metaphase II, resulting in fertilization failure (Sang et al., 2018). For a discussion of genetic heterogeneity of OZEMA, see 615774. [from OMIM]

Any primary ovarian failure in which the cause of the disease is a mutation in the FIGLA gene. [from MONDO]

Female infertility due to zona pellucida defect is a rare, genetic, female infertility disorder characterized by the presence of abnormal oocytes that lack a zona pellucida. Affected individuals are unable to conceive despite having normal menstrual cycles and sex hormone levels, as well as no obstructions in the fallopian tubes or defects of the uterus or adnexa. [from ORDO]

Oocyte/zygote/embryo maturation arrest-6 (OZEMA6) is characterized by primary infertility due to defective sperm-binding to an abnormally thin zona pellucida (ZP) in patient oocytes. Successful pregnancy may be achieved by intracytoplasmic sperm injection in these patients (Dai et al., 2019). For a discussion of genetic heterogeneity of OZEMA, see 615774. [from OMIM]

Any inherited oocyte maturation defect in which the cause of the disease is a mutation in the TUBB8 gene. [from MONDO]

Any 46 XX gonadal dysgenesis in which the cause of the disease is a mutation in the PSMC3IP gene. [from MONDO]

Oocyte maturation defects due to mutation in PATL2 show phenotypic variability, with some oocytes exhibiting maturation arrest at the germinal vesicle stage and others at the metaphase I stage. In some patients, a few oocytes progress to polar body I; those oocytes either undergo fertilization failure or, in those that are fertilized, early embryonic arrest (Chen et al., 2017). [from OMIM]

Any primary ovarian failure in which the cause of the disease is a mutation in the POF1B gene. [from MONDO]

A rare genetic endocrine disorder characterized by persistently high prolactin serum levels (not associated with gestation, puerperium, drug intake or pituitary tumor) in multiple affected family members. Clinically it manifests with signs usually observed in hyperprolactinemia, which are: secondary medroxyprogesterone acetate (MPA)-negative amenorrhea and galactorrhea in female patients, and hypogonadism and decreased testosterone level-driven sexual disfunction in male patients. Oligomenorrhea and primary infertility have also been reported in some female patients. [from SNOMEDCT_US]

Hydatidiform mole is a human pregnancy with abnormal or no embryonic development and excessive trophoblastic proliferation. Partial hydatidiform moles have a triploid dispermic genome, with 2 sets of paternal chromosomes and 1 set of maternal chromosomes; complete hydatidiform moles have a diploid androgenetic genome with all chromosomes originating from 1 (monospermic) or 2 (dispermic) sperms, and no maternal chromosomes (summary by Nguyen et al., 2018). For a discussion of genetic heterogeneity of recurrent hydatidiform mole, see HYDM1 (231090). [from OMIM]

Oocyte/zygote/embryo maturation arrest-17 (OZEMA17) is characterized by female infertility due to arrest of the embryo after the first rounds of cleavage or failure to establish pregnancy after implantation (Wang et al., 2023). For a discussion of genetic heterogeneity of OZEMA, see 615774. [from OMIM]

Oocyte/zygote/embryo maturation arrest-7 (OZEMA7) is characterized by infertility due to oocyte death, which may occur before or after fertilization (Sang et al., 2019). For a discussion of genetic heterogeneity of OZEMA, see 615774. [from OMIM]

Oocyte/zygote/embryo maturation arrest-3 (OZEMA3) is characterized by infertility, caused by absence of the zona pellucida that results in degeneration of oocytes and 'empty follicle syndrome' on in vitro fertilization procedures (Chen et al., 2017). For a discussion of genetic heterogeneity of OZEMA, see 615774. [from OMIM]

Maternal genes play a critical role in the very early stages of embryonic development because of the lag in transcribing genes derived from the male pronucleus. TLE6 mutations are a rare cause of human female-limited fertility and appear to represent the earliest known human embryonic lethality that is due to a single gene mutation. In affected women, ovulation proceeds normally and the retrieved oocytes appear normal, but zygote formation is severely impaired (Alazami et al., 2015). For a general phenotypic description and discussion of genetic heterogeneity of OZEMA, see 615774. [from OMIM]

Hydatidiform mole is a human pregnancy with abnormal or no embryonic development and excessive trophoblastic proliferation. Partial hydatidiform moles have a triploid dispermic genome, with 2 sets of paternal chromosomes and 1 set of maternal chromosomes; complete hydatidiform moles have a diploid androgenetic genome with all chromosomes originating from 1 (monospermic) or 2 (dispermic) sperms, and no maternal chromosomes (summary by Nguyen et al., 2018). For a discussion of genetic heterogeneity of recurrent hydatidiform mole, see HYDM1 (231090). [from OMIM]

Oocyte/zygote/embryo maturation arrest-14 (OZEMA14) is characterized by female infertility due to oocyte maturation arrest, fertilization failure, and/or early embryonic arrest. The rare fertilized embryos that are transferred to the uterus fail to establish pregnancy after transfer (Zhao et al., 2020, Zhao et al., 2021, Huang et al., 2021, Xu et al., 2021). For a discussion of genetic heterogeneity of OZEMA, see 615774. [from OMIM]

Premature ovarian failure-22 (POF22) is characterized by female infertility, with small to atrophic ovaries and no visible ovarian follicles (Wu et al., 2022; Zhang et al., 2022). For a general phenotypic description and discussion of genetic heterogeneity of premature ovarian failure, see POF1 (311360). [from OMIM]

Progesterone prepares the endometrium for blastocyst implantation and allows maintenance of pregnancy. The major sources of progesterone are the corpus luteum during the second half of the menstrual cycle and at the beginning of pregnancy, and the placenta. The main hormones responsible for stimulation of progesterone secretion are luteinizing hormone (LH) for the corpus luteum of the menstrual cycle and chorionic gonadotropin for the corpus luteum of pregnancy. Complete end-organ resistance to progesterone would be incompatible with reproductive competence in females. Males would not be expected to be affected since progesterone has no known function in men. Failure of the uterus to respond to progesterone would lead to the development of a 'constantly proliferative' endometrium incompatible with blastocyst implantation. Partial resistance to progesterone, on the other hand, would be expected to be associated with various degrees of incomplete maturation of the endometrium, perhaps expressed clinically as infertility or early abortions. The syndrome would present with the clinical and histologic picture of a luteal phase defect in which the life span of the corpus luteum and the plasma progesterone concentrations would be normal or elevated. [from OMIM]