Who is the gate keeper for treatment in a fertility clinic in Germany? -baseline results of a prospective cohort study (PinK study).

BACKGROUND: It is estimated that 5-15% of all couples in industrialised nations are infertile. A perceived unfulfilled desire for a child or self-identification as infertile can lead to psychological strain and social isolation. About 53.000 women underwent assisted reproduction treatments in Germany in 2014. Little is known about the first medical consultation and patient needs prior to the first visit in a fertility clinic in Germany. The baseline survey of the prospective cohort study on couples undergoing fertility treatment in Germany (PinK Study) provides first results on this topic for Germany. METHODS: The baseline survey was conducted between 2012 and 2013. Self-administered questionnaires were handed out to patients of six fertility clinics at the beginning of treatment by clinic staff. At a participation rate of 31.0%, we were able to analyse data on 323 women and 242 men. RESULTS: 92.6% of the women had their initial medical consultation on their unfulfilled desire for a child with a gynaecologist. After the urologist (44.2%), the general practitioner (12.0%) was the second most approached initial contact person for men. 36.4% of all men had no medical consultation on the unfulfilled desire for a child before visiting a fertility clinic. 46.9% of the respondents expressed the wish that the conversation about infertility should be initiated by a physician. Prior to their first visit to a fertility clinic, 11.2% of the men and 24.8% of the women were informed by a physician that infertility treatment can cause emotional strain. CONCLUSION: While almost all women consult a gynaecologist prior to the first visit in a fertility centre, one out of three men do not consult any physician at that stage. For the remaining group of men, urologists and general practitioners are the most important contact persons. Gender-specific health care needs are evident. In order to close the health care gap for men in Germany, more opportunities for discreet access to consultation should be offered. Due to its low threshold and family-oriented approach, general practice could make an important contribution to this effect.

The effect of ovarian stimulation on the outcome of intrauterine insemination.

PURPOSE: Although intrauterine insemination is one of the oldest techniques in reproductive medicine, its significance is still controversially discussed. Many factors have been reported as influencing pregnancy rates after IUI. The aim of this retrospective analysis is to evaluate the success rate of repeated inseminations depending on the type of ovarian stimulation. METHODS: Patients who underwent intrauterine insemination in Wiesbaden Kinderwunschzentrum between 1998 and 2010, not older than 45 years of age, with male subfertility were included in this study. On the whole, 5,346 inseminations on 2,180 patients were analyzed retrospectively. RESULTS: Females' mean age was 34.1, ranging from 19-45 years. In 433 cycles an insemination was performed during a natural cycle. 4,020 cycles were stimulated with recombinant FSH, 596 cycles with clomiphene, 194 with urinary FSH, 103 with HMG. The pregnancy rates range from 7.4% in the clomiphene group to 14.4% in the urinary FSH group. Clomiphene stimulation seems to offer the significantly lowest pregnancy rate (p = 0.03). The other types of stimulation do not differ significantly from each other concerning the pregnancy rate. Patients under 39 years of age do not profit from any ovarian stimulation. In 40 and more years of old patients, pregnancy rates are higher, if any stimulation was performed. CONCLUSION: To sum up, clomiphene stimulation showed to offer significantly lower pregnancy rates in comparison to the natural cycle, FSH stimulation and HMG stimulation in IUI treatment. While women younger than 40 seem not to profit from any ovarian stimulation, women over 40 do profit.

The Association of Appendectomy, Adhesions, Tubal Pathology, and Female Infertility.

BACKGROUND AND OBJECTIVES: The aim of the study was to investigate a potential association between previous childhood appendectomy, tube pathology, and female infertility. METHODS: We reviewed patients seeking care at the fertility clinic of our university medical center between 2006 and 2016. The history of previous appendectomy was extracted from hospital documentation and by telephone follow-up. Tubal patency was assessed by diagnostic laparoscopy and chromopertubation. RESULTS: In our study cohort (N = 237), 24.9% (n = 59) had a history of previous appendectomy. Previous appendectomy, therefore, was about 3-fold more prevalent in women seeking fertility treatment than in the general population. Patients with previous appendectomy had more intra-abdominal adhesions (P < .001) and patients with adhesions tended to have compromised tubal patency (P = .05). However, there was no direct correlation between a previous appendectomy and tube pathology (P = .727). CONCLUSION: Because previous appendectomy was associated with intra-abdominal adhesions, and these were in turn associated with tube pathology, but appendectomy was not directly associated with compromised tubal patency, previous appendectomy may indirectly affect female fertility through mechanisms other than direct tubal obstruction. This is one of the largest study analyzing laparoscopic chromopertubation in association with previous childhood appendectomy.

Fertility in males after childhood, adolescent, and adult inguinal operations.

BACKGROUND/PURPOSE: Inguinal hernia repair and orchidopexy are among the most common operations in boys. The impact on future fertility has not been conclusively defined. This study evaluates sperm quality after previous inguinal surgery. METHODS: Spermiograms of men with a desire to conceive children were analyzed. History of previous inguinal surgery (hernia repair, orchidopexy, varicocele ligation) was correlated with sperm quality. Other influential factors (age, BMI, chronic medication, tobacco use) were also tested. RESULTS: A total of 333 patients were included. Overall, 12.6% of the subjects had undergone previous inguinal surgery. Of these, 17 (43%) were inguinal hernia repairs, 8 (20%) orchidopexies, and 6 (15%) varicocele ligations, while 9 (22%) could not give an exact history. Abnormal spermiograms were found in 60% (n = 24) of those with previous inguinal surgery versus 48% in controls (p = 0.16). On multivariate analysis, pathologic spermiogram parameters were associated with previous inguinal surgery, orchidopexy, use of chronic medication, and smoking, but NOT with inguinal hernia or varicocele repair alone. CONCLUSIONS: Previous inguinal hernia or varicocele repair does not seem to impact negatively on quality of sperm later in life. Orchidopexy, smoking, and use of chronic medication, however, were all associated with pathologic sperm quality parameters. TYPE OF STUDY: Prospective comparative study. LEVEL OF EVIDENCE: Level II.

Fertility After Ovarian Cystectomy: How Does Surgery Affect IVF/ICSI Outcomes?

Introduction For patients considering undergoing assisted reproductive techniques (ART), many concerns arise when persistent ovarian cysts are found. This large study aimed to determine how ovarian cyst removal affects success rates of IVF/ICSI therapies. Methods 550 patients who underwent an IVF/ICSI treatment between 2002 and 2011 with a persistent ovarian cyst ≤ 5 cm before treatment were analyzed retrospectively. 328 patients' preference was to undergo a laparoscopic cystectomy and 222 patients opted for a conservative management. Control subjects included 13 552 patients undergoing IVF/ICSI at the same period of time without an ovarian cyst. Results After adjusting for age, patients with ovarian cysts without surgery needed a significant higher stimulation dose than the control group (2576.4 vs. 2207.5 IU, p < 0.001). However, on average, they had 1.13 (- 0.25 - 2.01) higher oocyte number retrieved compared to the operated patients (9.0 ± 5.5 vs. 8.2 ± 5.0) (p = 0.012). Patients after surgical cyst removal had a significant lower number of oocytes retrieved (MNOR) in comparison to the control group (8.2 ± 5.0 vs. 9.5 ± 5.4) (p = 0.00). Compared to controls, operated patients had similar clinical pregnancy rate (CPR) (34.2 vs. 33.5%) OR 1.031 (95% CI 0.817 - 1.302) (p = 0.815). Compared to controls, patients without surgery showed significant lower pregnancy rate (34.2 vs. 25,7%) OR 1.428 (95% CI 1.054 - 1.936) (p = 0.002) and lower live birth rate (LBR) (21.9 vs. 13.5%) OR 1.685 (95% CI 1.143 - 2.485) (p = 0.008). Conclusions Ovarian cystectomy did not negatively impact the pregnancy rate or the live birth rate compared to controls.

Cancer and fertility preservation: fertility preservation in breast cancer patients.

Aggressive chemotherapy has improved the life expectancy for reproductive-age women with breast cancer, but it often causes infertility or premature ovarian failure due to destruction of the ovarian reserve. Many questions concerning fertility preservation in breast cancer patients remain unanswered--for example, whether fertility preservation methods interfere with chemotherapy, and whether subsequent pregnancy has negative effects on the prognosis. Fertility preservation is a critical factor in decision-making for younger breast cancer patients, however, and clinicians should address this. The present article reviews the incidence of chemotherapy-induced amenorrhea, and discusses fertility-preservation options and the prognosis for patients who become pregnant after breast cancer.

The effect of cancer treatment on female fertility and strategies for preserving fertility.

Aggressive chemotherapy and radiotherapy in young patients with cancer has greatly enhanced the life expectancy of these patients, but these treatments often cause infertility because of the massive destruction of the ovarian reserve resulting in premature ovarian failure (POF). This review focuses on the effect of cancer treatments on fertility and on the various surgical and assisted-reproduction innovations that are available to provide the patient with the option of future pregnancies. As the emerging discipline of fertility preservation is steadily attracting increasing interest, developments in the near future promise to be very exciting. However, in everyday routine work, better interdisciplinary cooperation between gynecological and pediatric oncologists, surgeons, immunologists and endocrinologists is necessary so that individualized options for fertility preservation can be offered in advance of surgical procedures or cancer treatments. GnRH analog treatment can preserve fertility in some patients, but not in all. At present, cryopreservation of ovarian tissue appears as a very promising method of providing the cancer patient with a realistic chance of preserving fertility-a prospect that is also extremely important to patients for psychological reasons.

Xenotransplantation of human ovarian tissue pieces in gonadotropin-stimulated SCID mice: the effect of ovariectomy.

The number of follicles were compared in different developmental stages after the cryopreservation of human ovarian tissue by open freezing system followed by xenotransplantation into severe combined immunodeficient (SCID)-mice under stimulation, with and without ovariectomy. Ovarian tissue, cryopreserved for fertility preservation was partly examined by LIVE/DEAD viability staining or was transplanted in the neck muscle of 32 SCID-mice. The development of follicles, estradiol production, vaginal cytology and uterus weight was assessed after 15 weeks under gonadotropin stimulation, with or without ovariectomy. Viable follicles were detected in all frozen/thawed specimens using the LIVE/DEAD assay. Ovariectomy caused a significant improvement of survival of follicles in the preantral and antral stages in the gonadotropin-stimulated animals (p < 0.001), whereas there was no significant effect on the primordial and primary follicle counts. In the non-ovariectomised group, only isolated primordial and primary follicles could be detected. The total follicle amount was significantly higher in the ovariectomised group (n=17, 9.2 +/- 7.8, mean +/-SD) than in the non-ovariectomized group (n=15, 0.3 +/- 1.0). This study demonstrates that ovariectomy of stimulated recipient SCID-mice is essential for the development of follicles after xenotransplantation of cryopreserved human ovarian grafts.

Gonadal damage and options for fertility preservation in female and male cancer survivors.

It is estimated that in 2010, 1 in every 250 adults will be a childhood cancer survivor. Today, oncological surgery, radiotherapy and chemotherapy achieve relatively high rates of remission and long-term survival, yet are often detrimental to fertility. Quality of life is increasingly important to long-term survivors of cancer, and one of the major quality-of-life issues is the ability to produce and raise normal children. Developments in the near future in the emerging field of fertility preservation in cancer survivors promise to be very exciting. This article reviews the published literature, discusses the effects of cancer treatment on fertility and presents the options available today thanks to advances in assisted-reproduction technology for maintaining fertility in male and female patients undergoing this type of treatment. The various diagnostic methods of assessing the fertility potential and the efficacy of in vitro fertilization (IVF) after cancer treatment are also presented.

Serum inhibin A, inhibin B, pro-alphaC, and activin A levels in women with idiopathic premature ovarian failure.

Serum inhibin A, inhibin B, pro-alphaC, and activin A levels in 30 women with idiopathic premature ovarian failure (POF), 30 postmenopausal women, and 30 age-matched fertile women were determined. Women with POF showed low levels of inhibin A and inhibin B, but not of activin A, whereas the levels of pro-alphaC were significantly higher than in postmenopausal women. Thus, the circulating level of pro-alphaC could be a marker for assessing residual ovarian function in women with POF.

Epigenetic heterogeneity of developmentally important genes in human sperm: implications for assisted reproduction outcome.

The molecular basis of male infertility is poorly understood, the majority of cases remaining unsolved. The association of aberrant sperm DNA methylation patterns and compromised semen parameters suggests that disturbances in male germline epigenetic reprogramming contribute to this problem. So far there are only few data on the epigenetic heterogeneity of sperm within a given sample and how to select the best sperm for successful infertility treatment. Limiting dilution bisulfite sequencing of small pools of sperm from fertile donors did not reveal significant differences in the occurrence of abnormal methylation imprints between sperm with and without morphological abnormalities. Intracytoplasmic morphologically selected sperm injection was not associated with an improved epigenetic quality, compared to standard intracytoplasmatic sperm injection. Deep bisulfite sequencing (DBS) of 2 imprinted and 2 pluripotency genes in sperm from men attending a fertility center showed that in both samples with normozoospermia and oligoasthenoteratozoospermia (OAT) the vast majority of sperm alleles was normally (de)methylated and the percentage of epimutations (allele methylation errors) was generally low (<1%). However, DBS allowed one to identify and quantify these rare epimutations with high accuracy. Sperm samples not leading to a pregnancy, in particular in the OAT group, had significantly more epimutations in the paternally methylated GTL2 gene than samples leading to a live birth. All 13 normozoospermic and 13 OAT samples leading to a child had <1% GTL2 epimutations, whereas one (7%) of 14 normozoospermic and 7 (50%) of 14 OAT samples without pregnancy displayed 1-14% GTL2 epimutations.

Reproduction beyond cancer: a message of hope for young women.

OBJECTIVE: Aggressive chemotherapy and radiotherapy or radical oncological surgery in young women with cancer has greatly enhanced these patients' life expectancy, but these treatments often cause infertility or premature ovarian failure due to a massive destruction of the ovarian reserve. The objective of this review is to discuss the effect of the various cancer treatments on fertility and present the various fertility sparing operations and fertility preservation strategies. METHOD: An extensive survey of the most up-to-date literature was performed. RESULTS: This review discusses the impact of current cancer treatment on fertility potential and the various surgical and assisted-reproduction innovations available today for the most common cancers in young women. Although the ability to retain reproductive potential is becoming a major quality-of-life factor in an increasing number of young female cancer survivors, they are still being poorly counseled with regard to the negative impact of the treatment on their fertility and on their options for fertility preservation. CONCLUSION: As the emerging discipline of fertility preservation is steadily attracting increasing interest, developments in the near future promise to be very exciting. However, in everyday routine work, better interdisciplinary cooperation between gynecological and pediatric oncologists, surgeons, immunologists, and endocrinologists is necessary so that individualized options for fertility preservation can be offered in advance of surgical procedures or cancer treatments.

Placenta-derived CD95 ligand causes liver damage in hemolysis, elevated liver enzymes, and low platelet count syndrome.

BACKGROUND & AIMS: The HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome is a life-threatening complication during pregnancy. The associated liver disease may be severe, and maternal hepatic complications may progress to the point that transplantation becomes necessary. CD95 (APO-1, Fas)-mediated apoptosis of liver cells is one of the major pathogenic mechanisms during liver disease. The interaction of CD95 with its ligand, CD95L(FasL), induces apoptosis and thus the source of the death-inducing ligand is critical for understanding the pathomechanism of liver damage involving the CD95-system. METHODS: Sera from HELLP patients were analyzed and used in cell culture experiments to study CD95-mediated apoptosis. We established a mouse model for placenta-induced liver damage and used a new therapeutical agent, LY498919, to block CD95 apoptosis. RESULTS: We describe apoptosis in the liver of HELLP patients and cytotoxic activity for primary human hepatocytes in HELLP serum. Blocking of CD95 signaling reduced the cytotoxic activity of HELLP serum. In addition, cytotoxic activity increased as HELLP syndrome developed. Furthermore, CD95L was found to be produced in the placenta and extracts of placenta were cytotoxic for human hepatocytes. Injection of mouse placenta extract in mice induces liver damage that could be prevented by blocking CD95L. CONCLUSIONS: Taken together, these data suggest that CD95L derived from the placenta acts systemically and is a primary cause of liver damage in HELLP syndrome. Our results also show that blocking of CD95L can reduce liver cell apoptosis, indicating that such a strategy may have therapeutic advantages.