Symptoms and General Pathology

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Neoplasms

Gland and Hormone Related Diseases

Nervous System Diseases

Musculoskeletal Diseases

Mouth and Tooth Diseases

Diseases and Abnormalities at or Before Birth

Rare Diseases

Syndrome

Infertility

Polycystic Ovary Syndrome

Anosmia

Cleft Palate

Cleft Lip

Hypogonadism

Puberty, Precocious

Amenorrhea

Cryptorchidism

Kallmann Syndrome

Gonadal Disorders

Endocrine System Diseases

Mouth Diseases

Stomatognathic Diseases

Congenital Abnormalities

Mouth Abnormalities

Stomatognathic System Abnormalities

Cysts

Ovarian Cysts

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Jaw Abnormalities

Jaw Diseases

Maxillofacial Abnormalities

Craniofacial Abnormalities

Musculoskeletal Abnormalities

Menstruation Disturbances

Disorders of Sex Development

Disorder of Sex Development, 46,XY

Urogenital Abnormalities

Male Urogenital Diseases

Genetic Diseases, Inborn

Precocious Puberty

Patients with reproductive disorders with or without cleft lip/palate will be recruited for:

* completion of medical questionnaire and review of medical records
* family tree (including questions on reproductive disorders and cleft lip/palate)
* specimen collection (DNA/RNA) from: serum/plasma/saliva/urine/buccal swab/hair follicles/sperm/skin biopsy
* smell testing
* hearing test
* bone density
* brain MRI
* kidney, testicular/ovarian ultrasound

Family members of Patients will be recruited for:

* completion of medical questionnaire
* specimen collection (DNA/RNA) from: serum/plasma/saliva/urine/buccal swab/hair follicles/sperm/skin biopsy
* smell testing

Emmanuelle Paccou

Michela Adamo, MD

Nelly Pitteloud, M.D.

The purpose of this study is to explore the genetic basis of reproductive disorders and cleft lip and/or palate.

The World Health Organization estimates approximately 10% of couples experience some sort of infertility problem.

In humans, puberty is the process through which we develop reproductive capacity.

The timing of puberty varies greatly in the general population and is influenced by both genetic and environmental factors. In extreme cases of pubertal delay, puberty progresses only partially or not at all and results in the clinical picture of congenital hypogonadotropic hypogonadism (CHH), either accompanied by anosmia in 50% of cases (Kallmann syndrome \[KS\]) or by normal sense of smell (nCHH), with a male: female ratio of 4:1.

CHH is due to GnRH deficiency (incidence 1: 4,000-10,000) and result in the failure of sexual maturation and infertility. It is genetically heterogeneous, with multiple patterns of inheritance and several associated loci. In the clinical spectrum of GnRH deficiency, CHH may also be associated with a cleft lip/palate (CL/P) in 5 to 7% of cases. However, this prevalence increases up to 40% in CHH patients carrying a mutation in a CL/P gene, suggesting a genetic overlap between CHH and CL/P.

Disorders of puberty have provided insight into the biology of reproduction and genetic technologies have enabled us to deepen understanding in this field. The focus of this study is to better understand the genetic control of puberty and human reproduction as well as its link with CL/P.

Increasing understanding of the molecular basis (genes) of inherited reproductive disorders and CL/P may enable investigators to:

* improve diagnostic testing and treatments for these problems
* develop new diagnostic tests and therapies for patients
* enhance counseling for patients and families with reproductive disorders
* enhance counseling for patients and families with cleft lip/palate

whole blood, serum/plasma, white blood cells, DNA

Genetics of Reproductive Disorders (Including Kallmann Syndrome) and Cleft Lip and/or Palate

The Genetics of Neuroendocrine Reproductive Disorders and of the Cleft Lip and/or Palate

The investigators aim to discover genes associated with reproductive disorders by identifying rare sequence variants (mutations) in patients

The investigators will use a variety of scientific approaches to assess the functional impact of the identified rare sequence variants (mutations)

The investigators will examine family pedigrees and study family members to determine the inheritance patterns (how the disorder is transmitted in the family)

The investigators will study the phenotypic spectrum (how the disorder presents clinically) in patients with identified rare sequence variants (mutations)

Swiss National Science Foundation

Centre Hospitalier Universitaire Vaudois

Professor of Medicine, Chief of Service

Hyperprolactinemia

Pituitary Diseases

Hypothalamic Diseases

Brain Diseases

Central Nervous System Diseases

Galactorrhoea-Hyperprolactinaemia

All Drugs and Chemicals

Hormones

Hormone Antagonists

Intravenous (IV) or subcutaneous (SC) administration of kisspeptin 112-121 and/or administration of GnRH

One or more IV or SC doses of kisspeptin 112-121, and/or short infusion (up to 12 hours) of kisspeptin 112-121

kisspeptin 112-121

One or more IV doses of GnRH, and/or SC administration of GnRH

GnRH

Study Coordinator

Stephanie B Seminara, MD

Yee-Ming Chan, MD, PhD

Margaret Lippincott, MD

The goal of this study is to learn about the role of kisspeptin in the reproductive system. Kisspeptin is a naturally occurring hormone in humans that causes the release of other hormones, including gonadotropin-releasing hormone (GnRH) in the body.

The reproductive hormone GnRH is essential for normal reproductive function. People with idiopathic hypogonadotropic hypogonadism (IHH), hyperprolactinemia, and polycystic ovarian syndrome (PCOS) do not secrete or respond to GnRH in a normal way. In this study, investigators will give participants kisspeptin-a hormone that is naturally found in the human body and is known to be a powerful stimulus of GnRH secretion. They may also give participants GnRH to determine if participants will be able to fully respond to kisspeptin. The goal of this study is to use kisspeptin administration to probe the condition of GnRH neurons in people with various reproductive disorders to better understand the underlying reasons for the disorders. Investigators hope to gain new insights into GnRH neuronal function (or dysfunction) that will lead to better diagnostics in the future.

Kisspeptin Administration in the Adult

Administration of Kisspeptin to Subjects With Reproductive Disorders

Massachusetts General Hospital

Chief, Reproductive Endocrine Unit; Professor of Medicine, Harvard Medical School; Director, MGH Harvard Center for Reproductive Medicine

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Genetics of Reproductive Disorders (Including Kallmann Syndrome) and Cleft Lip and/or Palate	NCT01601171	Kallmann Syndro... Hypogonadotropi... Hypothalamic Am... Polycystic Ovar... Precocious Pube... Cleft Lip and P... Cleft Palate Cleft Lip		-	Centre Hospitalier Universitaire Vaudois
Kisspeptin Administration in the Adult	NCT00914823	Hypogonadotropi... Kallmann Syndro... GnRH Deficiency PCOS Polycystic Ovar... Hyperprolactine...	kisspeptin 112-... GnRH	18 Years -	Massachusetts General Hospital

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