Fertility: Infection and Inflammation

The investigators aim to investigate whether inflammatory and inflammation-inducing factors detectable in the collected samples, as well as infections present in these samples, are altered in cases of fertility issues and whether these factors could be predictive of pregnancy progression and child outcomes. Specifically, factors that mediate inflammation-acting either pro-inflammatory or anti-inflammatory-will be examined for their association with pregnancy establishment. This includes, for example, signaling molecules such as cytokines, metabolic and endocrinological parameters that may contribute to a pro-inflammatory milieu (e.g., hyperglycemia, blood lipids, hormones), viral infections that may influence fertility (e.g., human papillomavirus (HPV), herpesviruses). Additionally, a standard blood panel will be performed.

Fertility issues are increasing in both women and men. The causes are not only due to the higher age of couples wishing to conceive but also to infections, environmental factors (e.g., environmental toxins), and lifestyle-associated factors (e.g., BMI, increased body fat percentage, and diabetes). The fertilization of the egg and the implantation of the embryo into the endometrium is a highly complex process influenced by many factors. The egg, sperm, embryo, and endometrium all play a crucial role. Essential are, on the one hand, factors secreted by these components, which are present in maternal blood, follicular fluid, or ejaculate, and on the other hand, factors produced by the mother that influence the egg, fertilization, embryo, and endometrium.

Inflammatory processes, such as those occurring due to viral or bacterial infections, metabolic dysregulations (diabetes or obesity), or exposure to environmental substances (environmental toxins), may alter the normal milieu and thereby affect fertilization and implantation. In the context of assisted reproductive technologies (in vitro fertilization, IVF), the investigators have the opportunity to analyze samples that are not accessible during natural conception. These samples allow us to identify the presence of inflammatory processes and investigate their impact on pregnancy establishment.

1. Sample Collection:

   In the diagnostic cycle-a cycle preceding further fertility treatment, during which possible causes of infertility are assessed-blood samples in both the early and late follicular phase (cycle days 2-5 and 19-21) will be collected and an endometrial sample (7 days after ovulation). Additionally body composition (including body fat percentage) is measured in the BOD POD and via ultrasound.

   During oocyte retrieval, the investigators collect blood, follicular fluid (individually the primordial follicle, the rest pooled, and a microbiological vaginal swab. Moreover, body composition is again measured in the BOD POD. From the male partner the investigators collect a blood sample and an aliquot of the ejaculate.

   After in vitro fertilization (IVF), the culture medium in which the fertilized egg develops into a blastocyst is collected.

2. Sample Analysis:

In blood samples and follicular fluid, the investigators will analyze signaling molecules (hormones, cytokines, etc.), Metabolites (including amino acids, bile acids), Proteins, RNA molecules, cell-free DNA, oligosaccharides, and immune cells. For some follicular fluid samples, granulosa cells will be separated by centrifugation and cultured. Body composition/% body fat will be measured.

The main readout is the establishment of a clinical pregnancy. However, additional clinical information about the patient is also considered, including reason for IVF treatment, diagnosis, relevant pre-existing conditions, surgeries, or long-term medication use, smoking status, anti-Müllerian hormone (AMH) levels, stimulation protocol, duration of pregnancy. Furthermore, clinical information about the neonate is collected, including birth weight, birth length, and sex.

Additionally, the following fertility diagnostic parameters are documented and analyzed: Antral follicle count (AFC), number of preovulatory follicles, number of follicles on the for their association with pregnancy establishment. This includes, for example, signaling
 molecules such as cytokines, metabolic and endocrinological parameters that may
 contribute to a pro-inflammatory milieu (e.g., hyperglycemia, blood lipids, hormones),
 viral infections that may influence fertility (e.g., human papillomavirus (HPV),
 herpesviruses). Additionally, a standard blood panel will be performed.
 
 Fertility issues are increasing in both women and men. The causes are not only due to the
 higher age of couples wishing to conceive but also to infections, environmental factors
 (e.g., environmental toxins), and lifestyle-associated factors (e.g., BMI, increased body
 fat percentage, and diabetes). The fertilization of the egg and the implantation of the
 embryo into the endometrium is a highly complex process influenced by many factors. The
 egg, sperm, embryo, and endometrium all play a crucial role. Essential are, on the one
 hand, factors secreted by these components, which are present in maternal blood,
 follicular fluid, or ejaculate, and on the other hand, factors produced by the mother
 that influence the egg, fertilization, embryo, and endometrium.
 
 Inflammatory processes, such as those occurring due to viral or bacterial infections,
 metabolic dysregulations (diabetes or obesity), or exposure to environmental substances
 (environmental toxins), may alter the normal milieu and thereby affect fertilization and
 implantation. In the context of assisted reproductive technologies (in vitro
 fertilization, IVF), the investigators have the opportunity to analyze samples that are
 not accessible during natural conception. These samples allow us to identify the presence
 of inflammatory processes and investigate their impact on pregnancy establishment.
 

1. Sample Collection:
 
 In the diagnostic cycle-a cycle preceding further fertility treatment, during which
 possible causes of infertility are assessed-blood samples in both the early and late
 follicular phase (cycle days 2-5 and 19-21) will be collected and an endometrial
 sample (7 days after ovulation). Additionally body composition (including body fat
 percentage) is measured in the BOD POD and via ultrasound.
 
 During oocyte retrieval, the investigators collect blood, follicular fluid
 (individually the primordial follicle, the rest pooled, and a microbiological
 vaginal swab. Moreover, body composition is again measured in the BOD POD. From the
 male partner the investigators collect a blood sample and an aliquot of the
 ejaculate.
 
 After in vitro fertilization (IVF), the culture medium in which the fertilized egg
 develops into a blastocyst is collected.
 
2. Sample Analysis:
 

In blood samples and follicular fluid, the investigators will analyze signaling molecules
 (hormones, cytokines, etc.), Metabolites (including amino acids, bile acids), Proteins,
 RNA molecules, cell-free DNA, oligosaccharides, and immune cells. For some follicular
 fluid samples, granulosa cells will be separated by centrifugation and cultured. Body
 composition/% body fat will be measured.
 
 The main readout is the establishment of a clinical pregnancy. However, additional
 clinical information about the patient is also considered, including reason for IVF
 treatment, diagnosis, relevant pre-existing conditions, surgeries, or long-term
 medication use, smoking status, anti-Müllerian hormone (AMH) levels, stimulation
 protocol, duration of pregnancy. Furthermore, clinical information about the neonate is
 collected, including birth weight, birth length, and sex.
 
 Additionally, the following fertility diagnostic parameters are documented and analyzed:
 Antral follicle count (AFC), number of preovulatory follicles, number of follicles on the
 day of oocyte retrieval, number of retrieved oocytes, follicular Output Rate (FORT), follicle-to-Oocyte Index (FOI), oocyte utilization rate, oocyte maturation status (MII, MI, GV, zona pellucida), fertilization method (IVF, ICSI), pronucleus classification (PN1-4), fertilization rate, mnumber of blastocysts, blastocyst morphology, blastocyst formation rate, eEmbryo quality, fresh or frozen embryo transfer, implantation rate, biochemical pregnancy rate, miscarriage rate, live birth rate.

Experimental parameters will be evaluated using clinical findings to gain a comprehensive understanding of patient fertility, response to IVF treatment, and, if applicable, pregnancy progression.

Control Groups The control group consists of samples from couples in whom infertility is attributed solely to the male partner (serving as a control for female patient samples) or solely to the female partner (serving as a control for male partner samples).

All samples are pseudonymized by research nurses before analysis.