Verena Nordhoff

Universitätsklinikum Münster | UKM · Centre of Reproductive Medicine and Andrology

Medically assisted reproduction (MAR) includes all techniques used to achieve pregnancies not only in case of human infertility, but also for the in vitro production of embryos in the livestock industry, and for the conservation of endangered species. Focusing on humans only, the total number of babies born worldwide (thanks to MAR) has been estima...

To locate and fertilize the egg, sperm probe the varying microenvironment prevailing at different stages during their journey across the female genital tract. To this end, they are equipped with a unique repertoire of mostly sperm-specific proteins. In particular, the flagellar Ca²⁺ channel CatSper has come into focus as a polymodal sensor used by...

Study question Are there differences in fertilization and pregnancy rates post-TESE-ICSI between motile and immotile sperm, and do these vary in treatments with and without calcium ionophore? Summary answer Post-TESE-ICSI data reveals differences in fertilization and pregnancy rates when comparing motile vs. immotile sperm and treatments with and...

Male infertility and meiotic arrest have been linked to M1AP, the gene encoding meiosis I associated protein. In mice, M1AP interacts with the ZZS proteins SHOC1, TEX11, and SPO16, which promote DNA crossover formation during meiosis. To determine whether M1AP and ZZS proteins are involved in human male infertility by disrupting crossover formation...

Background Cytotoxic treatments such as chemo- and radiotherapy and immune therapies are required in cancer diseases. These therapies have the potential to cure patients but may also have an impact on gonadal function and, therefore, on fertility. Consequently, fertility preservation treatments such as freezing of gametes and gonadal tissue might b...

STUDY QUESTION Are there subgroups among patients with cryptozoospermia pointing to distinct etiologies? SUMMARY ANSWER We reveal two distinct subgroups of cryptozoospermic (Crypto) patients based on testicular tissue composition, testicular volume, and FSH levels. WHAT IS KNOWN ALREADY Cryptozoospermic patients present with a sperm concentration...

The infertility of many couples rests on an enigmatic dysfunction of the man's sperm. To gain insight into the underlying pathomechanisms, we assessed the function of the sperm-specific multisubunit CatSper-channel complex in the sperm of almost 2,300 men undergoing a fertility workup, using a simple motility-based test. We identified a group of me...

Semen is analyzed for both diagnostic and prognostic purposes. Whether spermatozoa are present, in what numbers and in what condition (viable, motile, morphologically normal), are useful indicators that reflect testicular, epididymal, and accessory gland function and provide information on the quality of semen transferred at coitus. As variation in...

Despite a plethora of methods that provide further information on spermatozoa quality and functions, only a few sperm function tests are routinely used in the andrology laboratory. Numerous of these tests for diagnosing fertility disorders examine only single isolated aspects of spermatozoa and do not necessarily reflect the situation in vivo. More...

Successful fertilization of an egg is the ultimate goal of a mature sperm. For this process to occur correctly in vivo, the natural fertilization process follows a time- and location-dependent sequence of complex steps, beginning with production in the testis, maturation in the epididymis, and finally the fertilization of the egg. Specific proteins...

In-vitro fertilization (IVF) is a procedure practised worldwide, with patients and practitioners expecting higher live birth rates and excellent standards of quality as methodologies become more established. This practical book covers every stage in the life of an IVF laboratory, from designing and planning the laboratory to training the embryologi...

BACKGROUND Cytotoxic treatments such as chemo- and radiotherapy and immune therapies are required in cancer diseases. These therapies have the potential to cure patients but may also have an impact on gonadal function and, therefore, on fertility. Consequently, fertility preservation treatments such as freezing of gametes and gonadal tissue might b...

Medically assisted reproduction (MAR) has continuously developed since the first successful steps over 40 years ago. For example, culture media and culture environment are far more complex than they were in the beginning and can optimally support the pre-implantation development of the embryos until transfer. However, the biggest challenge for the...

Study question Is a loss of CatSper function in sperm a common cause of unexplained male infertility? Summary answer Loss of CatSper function leads to similar infertility phenotypes in mice and men and represents one of the most common causes of unexplained male infertility. What is known already Male infertility is often due to low sperm counts,...

The infertility of many couples seems to rest on an enigmatic dysfunction of the men's sperm, rendering early diagnosis and evidence-based treatment by medically assisted reproduction impossible. Using a novel laboratory test, we assessed the function of the flagellar calcium channel CatSper in sperm of almost 2,300 men undergoing a fertility worku...

Die Untersuchung des Ejakulates dient der Diagnostik und Prognose der männlichen Fertilität. Ob Spermatozoen vorhanden sind, in welcher Anzahl und in welchem Zustand (vital, beweglich, morphologisch normal), sind nützliche Indikatoren, die die Funktion des Hodens, des Nebenhodens und der akzessorischen Geschlechtsdrüsen widerspiegeln und Informatio...

Growth factors became attractive candidates for medium supplementation to further improve the quality of embryo culture and to mimic in vivo nutrition. Granulocyte macrophage colony-stimulating factor (GM-CSF) is a cytokine influencing the maternal-fetal interface and supporting placental development in mouse and human. It is expressed in epithelia...

Study question Is the sperm retrieval rate of a small, pre-processed sample (PPS) of each TESE-biopsy representative for the sperm outcome on the day of ICSI? Summary answer The analysis of a PPS reliably reflects the probability of finding comparable numbers of sperm at time of TESE-ICSI. What is known already Azoospermia is defined as a conditi...

The sperm-specific Ca2+ channel CatSper registers chemical cues that assist human sperm to fertilize the egg. Prime examples are progesterone and prostaglandin E1 that activate CatSper without involving classical nuclear and G protein-coupled receptors, respectively. Here, we study the action of seminal and follicular fluid as well of the contained...

Introduction Supporting and counselling couples with fertility issues prior to starting ART is a multidisciplinary diagnostic and therapeutic challenge. The first German-language interdisciplinary S2k guideline on “Diagnosis and Therapy Before Assisted Reproductive Treatments (ART)” was published in February 2019. The guideline was developed in the...

For an optimal outcome in assisted reproductive treatment (ART), the preparation and selection of the appropriate sperm or sperm population is an absolute prerequisite. A wide range of different preparation methods and functional assays are available. In addition to the classical World Health Organization methods like simple washing, the swim-up te...

It is widely held that the first two blastomeres of mammalian embryos are equally totipotent and that this totipotency belongs in the group of the regulative properties. However, this interpretation neglects an important aspect: evidence only came from successful monozygotic twins which can speak only for those pairs of half-embryos that are able t...

Assisted reproductive technologies (ART) include all techniques used to achieve pregnancies not only in case of human infertility, but also for the in vitro production of embryos in the livestock industry, and for the conservation of endangered species. Focusing on human ART only, the total number of babies born worldwide has been estimated to more...

Since long we know that genetic mutations are able to influence the expression of our genes. However, in the last 10-15 years it became evident that not only alterations in the genetic code but also other modifications are able to trigger changes in the RNA profile of a cell. The so called epigenetic modification can modify the DNA without changing...

Context Testicular sperm extraction (TESE) followed by assisted reproductive techniques often remains the only therapeutic option for men presenting with azoospermia due to spermatogenic failure. Reproductive parameters, such as gonadotropin levels, testicular volume or histopathology, contribute to the prediction of sperm retrieval rate (SRR) in T...

Aim The aim of this official guideline published by the German Society of Gynecology and Obstetrics (DGGG) and coordinated with the German Society of Urology (DGU) and the German Society of Reproductive Medicine (DGRM) is to provide consensus-based recommendations, obtained by evaluating the relevant literature, on counseling and fertility preserva...

Study question: What is the prevalence, reproducibility and biological significance of transcriptomic differences between sister blastomeres of the mouse 2-cell embryo? Summary answer: Sister 2-cell stage blastomeres are distinguishable from each other by mRNA analysis, attesting to the fact that differentiation starts mostly early in the mouse...

The de novo creation of spermatozoa is an important task in reproductive research. Patients with spermatogenic defects, especially those impacted by gonadotoxic oncological treatments, would benefit from this approach. Several in vitro methods for differentiation of spermatogonia into sperm are under development. These approaches include organ cult...

Following fertilization in mammals, it is generally accepted that totipotent cells are exclusive to the zygote and to each of the two blastomeres originating from the first mitotic division. This model of totipotency was inferred from a minority of cases in which blastomeres produced monozygotic twins in mice. Was this due to experimental limitatio...

Introduction Spermatozoa have to be separated from seminal fluid to omit negative influences and to ensure best assisted reproductive technology (ART) results. Several preparation techniques exist that can be used to enrich the best motile and morphologically normal spermatozoa: (1) simple washing, (2) swim-up (with or without washing step) and (3)...

The optimization of in-vitro culture conditions and the selection of the embryo(s) with the highest developmental competence are essential components in an ART program. Culture conditions are manifold and they underlie not always evidence-based research but also trends entering the IVF laboratory. At the moment, the idea of using sequential media a...

Intracytoplasmic sperm injection (ICSI) using spermatozoa from patients with severe oligoasthenoteratozoospermia is still a challenge. Although spermatozoa are available, lower fertilisation rates as well as compromised pregnancy rates are observed after ICSI. We aimed at identifying respective parameters in the pre-values of ejaculate samples used...

A common feature of assisted reproductive techniques such as IVF or intracytoplasmic sperm injection is the IVC of oocytes or preimplantation embryos in artificial culture media. The IVC conditions are selected to mimic the environment of the female genital tract. We have shown that murine preimplantation embryos respond to different culture media...

Imprinted genes are expressed either from the paternal or the maternal allele, because the other allele has been silenced in the mother's or father's germline. Imprints are characterized by DNA methylation at CpG sites. Recently, abnormal sperm parameters and male infertility have been linked to aberrant methylation patterns of imprinted genes in s...

A viable spermatozoon is the prerequisite for initiating fertilization in intracytoplasmic sperm injection. Usually motility is the primary sign used to determine a sperm's viability. However, in every in vitro fertilization (IVF) laboratory cases are observed in which none or only few spermatozoa are motile. This can occur in treatment cycles invo...

The present study demonstrates the feasibility of application of a microfluidic system for in vitro culture of pre-implantation mouse embryos, with subsequent development to full-term upon embryo transfer. Specifically, embryos cultured in groups in nL volume chambers achieve pre-implantation developmental rates up to 95% (4.5 days after fertilizat...

Is post-implantation embryonic development after blastocyst transfer affected by exposure to different assisted reproduction technology (ART) culture media? Fetal development and placental histology of ART embryos cultured in vitro in different ART media was not impaired compared with embryos grown in vivo. The application of different in vitro cul...

For most azoospermic men testicular sperm extraction (TESE) is the only treatment, however it presents challenges for the ART laboratory, as the retrieval of motile spermatozoa is difficult. In the absence of sperm movement no unequivocal distinction can be made between either dead or immotile, but vital spermatozoa. However, a single laser shot di...

Human embryo culture media, intended for assisted reproductive technologies (ARTs), are released for clinical use if they pass the mouse embryo assay (MEA). This assay prescribes that at least 70% of in vivo fertilized mouse 1-cell embryos form blastocysts, in order to grant the culture medium approval. In the fertility clinic, however, human embry...

Study question: Do different human ART culture protocols prepare embryos differently for post-implantation development? Summary answer: The type of ART culture protocol results in distinct cellular and molecular phenotypes in vitro at the blastocyst stage as well as subsequently during in vivo development. What is known already: It has been re...

The study was designed to evaluate in vitro the cellular mechanisms of the single nucleotide polymorphism (SNP) p.N680S of the FSH receptor gene (FSHR) in human granulosa cells (GC) and included patients homozygous for the FSHR SNP (NN/SS) undergoing ovarian stimulation. GC were isolated during oocyte retrieval and cultured for 1–7 days. Basal oest...

There is no systematic study on coiled sperm in semen, although they are commonly observed. This work characterizes coiled sperm in infertile men to understand the clinical implications and investigate the possible cause by osmotic swelling. Coiled sperm in semen from 439 infertile patients were quantified and their ultrastructure examined by elect...

To assess individual chances for a live-born child in azoospermic men by performance of testicular sperm extraction (TESE) followed by intracytoplasmatic sperm injection (ICSI). A retrospective cohort study. An academic fertility care center and research unit. Two hundred three couples who wished to have a child; all men had azoospermia. All men we...

To specifically express the Asp567Gly human follicle-stimulating hormone receptor (FSHR) under the control of its promoter to evaluate the phenotypic consequences in the presence of normal pituitary function. We produced transgenic mice overexpressing the Asp567Gly human FSHR under the control of a 1.5kb 5'-flanking region fragment of its promoter....

Smoking by one or both partners can adversely affect IVF outcome. We investigated whether smoking may also play a role in the success rate of intracytoplasmic sperm injection (ICSI), in which initial steps of fertilization are bypassed. Three hundred one couples (ICSI: 153, IVF: 148) participated in 415 treatment cycles (ICSI: 202, IVF: 213). One h...

FSH mediates its testicular actions via a specific Sertoli cell G protein-coupled receptor. We created a novel transgenic model to investigate a mutant human FSH receptor (FSHR(+)) containing a single amino acid substitution (Asp567Gly) equivalent to activating mutations in related glycoprotein hormone receptors. To examine the ligand-independent g...

The Oct-4 gene encodes a transcription factor that is specifically expressed in embryonic stem cells and germ cells of the mouse embryo. Cells that differentiate into somatic tissues lose Oct-4 expression. Regulation of Oct-4 gene transcription involves a TATA-less minimal promoter and two upstream elements: the proximal (PE) and distal enhancers (...

Activating mutations of the luteinizing hormone receptor (LHR) and the follicle-stimulating hormone receptor (FSHR) have been known for several years. These activating mutations permanently stimulate, in the absence of their cognate ligand, the receptor signaling pathways. In the case of the LHR, the induced chronic stimulation causes sporadic and...

Activating mutations of the luteinizing hormone receptor (LHR) and the follicle-stimulating hormone receptor (FSHR) have been known for several years. These activating mutations permanently stimulate, in the absence of their cognate ligand, the receptor signaling pathways. In the case of the LHR, the induced chronic stimulation causes sporadic and...

This study investigated whether the gene for peripherin, a protein previously considered to play only a role in the retina, may also be expressed in the pineal gland of both Djungarian hamsters (Phodopus sungorus) and humans. After extraction of mRNA from pooled pineal glands of hamsters and from one human pineal gland, mRNA was transcribed into cD...

Münster (Westfalen), Univ., Diss., 1999.

We describe a patient with onset of puberty at the age of 5 yr. characterized by accelerated growth, enlargement of genitalia, pubarche, and serum hormone levels compatible with noncentral precocious puberty. Exon 11 of the LH receptor gene was amplified from genomic DNA by PCR and directly sequenced. We identified a heterozygous C to T base change...

The follicle-stimulating hormone (FSH) is essential for normal gametogenesis. In females FSH is required for ovarian development and follicle maturation whereas in males FSH determines Sertoli cell number and quantitatively and qualitatively normal spermatogenesis. FSH action is mediated by a G-protein coupled receptor expressed solely in granulosa...

In holometabolous development, higher insects have two different life forms, the larva and the imago. Both larval and imaginal cells are derived from cells of the blastoderm stage. After the final embryonic wave of mitosis, however, only the imaginal cells remain diploid, proliferate massively and do not differentiate until metamorphosis. The separ...