Pregnancy after vitrification of pronuclear stage oocytes biopsied for polar body aneuploidy screening.

This paper reports the case of a patient undergoing IVF and polar body analysis for aneuploidy screening because of advanced maternal age. A total of nine fertilized oocytes were obtained from the patient's third treatment cycle. Three supernumerary pronuclear stage oocytes were identified as suitable after aneuploidy screening for five chromosomes and vitrified. Because the fresh cycle did not result in a pregnancy, vitrified pronuclear stage oocytes were warmed for transfer in an artificial cycle. All three zygotes survived warming and were transferred to the patient's uterus 2 days later as 4-, 5- and 6-cell stage embryos. After 2 weeks, a positive pregnancy test indicated successful implantation. The gestation is developing normally and is presently (end of September 2007) in the 22nd week.

A new paradigm for profiling testicular gene expression during normal and disturbed human spermatogenesis.

The aim of this study was to identify gene expression patterns of the testis that correlate with the appearance of distinct stages of male germ cells. We avoided the pitfalls of mixed pathological phenotypes of the testis and circumvented the inapplicability of using the first spermatogenic wave as done previously on rodents. This was accomplished by using 28 samples showing defined and highly homogeneous pathologies selected from 578 testicular biopsies obtained from 289 men with azoospermia (two biopsies each). The molecular signature of the different developmental stages correlated with the morphological preclassification of the testicular biopsies, as shown by resampling-based hierarchical clustering using different measures of variability. By using analysis of variance (ANOVA) and extensive permutation analysis, we filtered 1181 genes that exhibit exceptional statistical significance in testicular expression and grouped subsets with transcriptional changes within the pre-meiotic (348 genes), post-meiotic (81 genes) and terminal differentiation (38 genes) phase. Several distinct molecular classes, metabolic pathways and transcription factor binding sites are involved, depending on the transcriptional profile of the gene clusters that were built using a novel clustering procedure based on not only similarity but also statistical significance.

Reduced incidence of ovarian hyperstimulation syndrome by prophylactic infusion of hydroxyaethyl starch solution in an in-vitro fertilization programme.

Prophylactic infusion of human serum albumin can reduce or mitigate severe ovarian hyperstimulation syndrome (OHSS) in patients at high risk. Recently, concern has been expressed in the lay press regarding the potential viral transmissions with blood constituents. Hence, we looked for a safe non-biological substitute with comparable physical properties in order to cope with this concern. One hundred patients of our in-vitro fertilization (IVF) programme with oestradiol serum concentrations > or = 11010 pmol/l on the day of human chorionic gonadotrophin injection and/or > or = 20 oocytes retrieved and/or previous severe OHSS were infused with 1000 ml 6% hydroxyaethyl starch solution at the time of oocyte collection and 500 ml 48 h later. A total of 82 IVF patients at risk without prophylactic infusions during the preceding years served as controls. Both groups were identical according to patient's age, body mass index, androgen concentrations, peak oestradiol concentrations, number of retrieved oocytes, fertilization and pregnancy rates. There were seven cases of severe OHSS in untreated patients and two cases in the treatment group (P = 0.08). In moderate OHSS a significant difference became obvious with only ten cases in the treatment group and 32 cases in the control group (P < 0.00001). Hydroxyaethyl starch solution seems to be an effective and economic alternative in reducing severe and moderate OHSS during IVF treatment.

Pregnancy after intracytoplasmic sperm injection of spermatozoa extracted from frozen-thawed testicular biopsy.

The case report illustrates the successful application of a new method of sperm extraction from frozen-thawed testicular biopsy specimen within an established programme of intracytoplasmic sperm injection.

Effects of clomiphene citrate stimulation on endometrial structure in infertile women.

Investigations into the effect of clomiphene citrate stimulation on endometrial differentiation were retrospectively performed in the mid-luteal phase on 21 patients undergoing ovulation induction prior to artificial insemination. A high incidence of irregular endometrial development was seen using morphological and morphometric criteria; in addition, increasing stromal oedema after clomiphene citrate treatment was observed. Measurable differences in glandular development (i.e. numbers of glands and glandular epithelial height) were found in early luteal phase biopsies (LH+2/+6) from patients treated with clomiphene citrate and normal fertile controls. Impaired endometrial development in the early luteal phase, which is a sensitive interval in preparation for implantation, might lead to an effective asynchrony between embryonic and uterine development and unfavourably influence the outcome of implantation.

Long-term follow-up in 206 infertility patients with polycystic ovarian syndrome after laparoscopic electrocautery of the ovarian surface.

In recent publications we have demonstrated that laparoscopic electrocautery of the ovarian surface (LEOS) is an effective method to reduce serum androgen concentrations, normalizing ovarian cycle length and the ovarian reaction to hormonal stimulation therapy in anovulatory patients with polycystic ovarian disease (PCOD). In this paper we show that these effects are not only temporary. Data from 206 patients undergoing LEOS and monitored for up to 72 months after surgery are evaluated; 145 patients achieved a total of 211 conceptions, giving a pregnancy rate of 70%, with a maximum of four conceptions in one patient. There were 38 early miscarriages (18%) and two late pregnancy losses as well as three ectopic implantations.

24-hour profiles of salivary progesterone.

OBJECTIVES: To assess whether the known pulsatility of P secretion by the corpus luteum, which is detected in blood by P measurements, translates into fluctuations of saliva P concentrations, and to determine how well saliva P measurements reflect plasma P concentration. A second objective was to see whether there is a window in the luteal phase, where P secretion has reached its maximum capacity, but the amplitude is not very accentuated, which would be an ideal time to measure P. DESIGN: Twenty-one ovulatory women were randomly assigned to be studied on day 5, 7, or 8 after the luteinizing hormone surge. Blood samples were drawn every 20 minutes, and saliva samples were obtained hourly over a 24-hour period. Comparison between saliva plasma P was performed, and pulse analysis of plasma P was done. RESULTS: The percent variation of saliva P concentration over a 24-hour period was much higher when compared with the percent variation of plasma P concentration over the same time period (saliva P: 149%; plasma P: 107%). Also, the ratio of saliva to plasma P varied significantly between individuals (range: 0.0050 to 0.0148). A single plasma P concentration (8:00 A.M.) correlated better with the 24-hour mean plasma concentration than the respective single saliva value or the mean of two or three saliva samples (8:00 A.M. and 12:00 P.M.; 8:00 A.M., 12:00 P.M., and 8:00 P.M.). Plasma pulse frequency, mean pulse interval, pulse width, pulse amplitude, and 24-hour mean P level did not differ between the 3 study days. CONCLUSIONS: A single plasma P determination reflects more accurately 24-hour P secretion than repeated saliva P samples measured in the same individual. We could not identify a window in the luteal phase when P measurements are more representative of corpus luteum function.

Laparoscopic electrocoagulation of the ovarian surface in infertile patients with polycystic ovarian disease.

OBJECTIVE: To assess the endocrinologic and clinical outcome after laparoscopic ovarian electrocautery because of polycystic reaction to ovarian stimulation in anovulatory infertility patients. DESIGN: Between 1986 and 1989, 133 patients with polycystic ovarian disease underwent laparoscopic electrocoagulation of the ovarian surface in an outpatient clinic after conventional ovarian stimulation had led to polycystic reaction. SETTING: All patients were referred to our outpatient clinic affiliated with the university hospital. RESULTS: The reduction of androgen levels and normalization of cycle length were highly significant. The overall pregnancy rate was 70% (73 of 104), ranging from 27% in smokers to 94% in nonsmoking couples. In 26 second-look operations de novo adhesions were found in 26.9% of the patients. CONCLUSION: Laparoscopic coagulation of the ovarian surface is an effective tool to reduce elevated androgen levels and to improve the intraovarian mechanism of selecting a dominant follicle. A postoperative complication may be adhesion formation.

Adhesion formation after laparoscopic electrocoagulation of the ovarian surface in polycystic ovary patients.

OBJECTIVE: To evaluate the incidence and extent of periovarian adhesion formation subsequent to laparoscopic electrocoagulation of the ovarian surface in infertility patients with polycystic ovarian disease (PCOD). DESIGN: From a total of 199 PCOD patients treated with ovarian electrocautery, 50 cases of laparoscopy and 12 cesarean sections served as second-look investigation. A subgroup of 30 patients had abdominal lavage and artificial ascites after surgery; they underwent "early" second-look (2 to 14 days after laparoscopy). SETTING: All patients were referred to our fertility outpatient clinic affiliated with the university hospital. PATIENTS: Infertility patients with polycystic ovarian reaction to hormonal stimulation therapy underwent laparoscopic electrocoagulation of the ovarian surface. RESULTS: Adhesion formation was detected in 19.3%; the incidence reduced to 16.6% with the use of abdominal lavage. The adhesions found were obviously due to bleeding of the ovarian capsule caused by electrocautery. Adhesiolysis was easily possible during "early" second-look. CONCLUSION: The incidence of de novo adhesion formation caused by laparoscopic electrocoagulation of the ovarian surface seems to be lower than after ovarian wedge resection; it can be reduced by abdominal lavage and artificial ascites.

Morphometric characteristics of endometrial biopsies after different types of ovarian stimulation for infertility treatment.

OBJECTIVE: To investigate whether various types of ovarian stimulation induce differences in endometrial development at the midluteal phase in infertile women. DESIGN: Assessment of stromal and glandular compartments in endometrial biopsies using morphometric criteria. SETTING: Institute for Hormone and Fertility Research, Hamburg, Germany. PATIENTS: The study included 18 women after treatment with human menopausal gonadotropin (hMG)/human chorionic gonadotropin (hCG) (group I), 23 women after clomiphene citrate (CC)/hMG/hCG treatment (group II), and 12 women after CC stimulation (group III). INTERVENTIONS: Endometrial biopsies and blood samples were taken simultaneously in the early to midluteal phase. To assess the time of ovulation, hormone analysis and regular checks by ultrasonography were performed. MAIN OUTCOME MEASURES: Morphometric evaluation of glandular and stromal structures revealed an impaired endometrial development after various treatment protocols. CONCLUSION: Ovarian stimulation in infertile women results in most cases in an elevation of steroid levels; however, the occurrence of an inadequate endometrial development might have an unfavorable influence on the outcome of implantation. Therefore, these findings may be of importance to the choice of treatment for infertility.

[Spontaneous conception after laparoscopic coagulation of the ovarian surfaces in a patient with primary normogonadotropic hyperandrogenemic amenorrhea]. / Spontankonzeption nach laparoskopischer Koagulation der Ovaroberflächen bei Patientin mit primärer normogonadotroper hyperandrogenämischer Amenorrhö.

A patient with primary amenorrhoea was kept under hormonal replacement therapy and oral contraceptives since the age of sixteen. At the age of 30 she first consulted the endocrinologist because of infertility after one year of "post-pill-amenorrhoea". This first hormone check detected a severe hypertestosteronaemia (1.3 ng/ml). During four stimulation cycles using gonadotropins she showed a polyfollicular reaction and finally developed a hyperstimulation WHO II. During the following cycle she underwent hystero- and laparoscopy; laparoscopic electrocoagulation of the ovarian surface (LEOS) was carried out during this treatment. She subsequently conceived spontaneously twice.

[Pregnancy onset without corpus luteum function?]. / Eintritt einer Gravidität ohne Corpus-luteum-Funktion?

Within five years, a patient had five abortions and one biochemical pregnancy with two different partners. After the fourth pregnancy, she underwent a heterologous immune stimulation. The karyotypes of all three partners were normal. On her first visit, a subclinical hypothyroidism was detected and substitution with 50 micrograms L-thyroxine was started. Before further endocrinological, virological, or anatomical investigation, the patient conceived spontaneously for the seventh time. Even though the beta-HCG-levels rose adequately and the sonographic development was according to time, serum-progesterone could not be detected before the eighth week of pregnancy and sufficient levels were found from the 15th week onwards. The patient received a hormonal substitution therapy with Gravibinon 250 mg i.m. twice a week up to the 15th week of gestation. She finally delivered a 3800 g healthy boy.

[Intrauterine pregnancy with uterine myoma after downregulation with GnRH analogs]. / Intrauterine Schwangerschaft in Uterus myomatosus nach Down-Regulation mit GnRH-Analogon.

GnRH analogues are widely used for the reduction of uterine fibroids. This case report describes the therapy of a 27-year-old woman, whose uterus had a diameter of about 13 cm. After 7 injections of Zoladex Depot (ICI Pharma, Heidelberg, Germany), the uterus was reduced to normal size carrying dorsally a myoma of the same size. After only 7 weeks of medroxyprogesterone acetate (5 mg twice daily, Clinofem, Upjohn, Heppenheim, Germany) the uterus had grown again, so that therapy was changed to Zoladex Depot for another 3 months. On the 27th day of the first spontaneous cycle, the patient ovulated and conceived. Up to the 29th week of gestation (Aug '91), the foetal growth and development was normal, the uterus was normal in size, a childhead sized myoma being situated unproblematically behind the foetus.

[Results of treatment with surface cauterization of polycystic ovaries in sterility patients]. / Behandlungsergebnisse mit der Oberflächen-kauterisierung polyzystischer Ovarien bei Sterilitätspatientinnen.

In 39 women with polycystic ovaries (PCO) and a history of sterility, laparoscopic electrocautery of the surface of the ovaries was performed by a technique adapted from Gjoennaess (1984). Previous hormonal treatment with clomiphene and/or human menopausal gonadotropins had been unsuccessful in these patients, whilst 23 of them (59%) conceived within one year after surgery. Electrocautery was followed by a decrease of mean testosterone levels from 0.95 +/- 0.064 ng/ml to 0.48 +/- 0.041 ng/ml and a similar decline of dehydroepiandrosterone sulfate from 2.9 +/- 0.136 g/ml to 1.6 +/- 0.165 g/ml respectively. Laparoscopic ovarian electrocautery is however associated with the risk of postoperative adhesion formation. Therefore we advise this form of surgery only, when hormonal therapy failed or if it presents an unacceptable high risk of hyperstimulation or a multiple pregnancy.

Patterns of serum-luteinizing hormone surges in stimulated cycles in relation to injections of human chorionic gonadotropin.

Endogenous-luteinizing hormone (LH) surges may complicate the management of in vitro fertilization cycles. To investigate the effects of LH surges after hormonal stimulation 53 IVF cycles were analyzed by assessing LH levels three times daily until egg collection. In 43% the LH rise started before the planned exogenous trigger for ovulation was given, in 11% the rise occurred simultaneously with and in 45% after the injection of human chorionic gonadotropin. Three main patterns of serum LH surges were identified: (A) low-LH tonus with straight increase to maximum; (B) low tonus with elevation before straight increase; (C) high tonus with large variations but no prominant peak. These patterns were not related to the follicular estradiol increase, luteal steroid concentrations or resulting pregnancy rates.