W. Küpker

Preserved pituitary response under ovarian stimulation with HMG and GnRH antagonists (Cetrorelix) in women with tubal infertility

OBJECTIVE To examine the pituitary response in patients undergoing short-term application of the GnRH antagonist Cetrorelix in the mid-cycle phase for hypophysial suppression of premature LH surges within an IVF-program. DESIGN Twenty patients suffering from primary or secondary tubal infertility were stimulated with hMG from cycle day 2. From day 7 till ovulation induction Cetrorelix was administered in two different dose regimens (15 patients 3 mg s.c. daily; 5 patients 1 mg s.c. daily). Three hours before ovulation induction a GnRH test was performed using 25 micrograms of native GnRH and the pituitary response examined by measurement of the serum LH concentration after 30 min. RESULTS Premature LH surges could be avoided in the 3-mg group and in the 1-mg group, respectively. Due to this, none of the cycles had to be cancelled. Oestradiol profiles and ultrasound demonstrated a satisfactory follicular maturation. All patients showed pronounced suppression of the serum LH levels before ovulation induction. The mean increase of serum LH due to the performed GnRH test was 10 mIU/ml for the 3-mg group, while the average maximum in the 1-mg group was about 32.5 mIU/ml. CONCLUSIONS The pituitary response is preserved by the treatment with the GnRH antagonist Cetrorelix. The extent of suppression of the adenohypophysis, as expressed by the different reactions on GnRH test, can be modulated by the dosage administered. This should allow ovulation induction by GnRH or one of its agonists instead of hCG, which could be beneficial in patients at high risk of Ovarian Hyperstimulation Syndrome (OHSS) and those suffering from Polycystic Ovary Disease (PCOD).

Hormone profiles under ovarian stimulation with human menopausal gonadotropin (hMG) and concomitant administration of the gonadotropin releasing hormone (GnRH)-antagonist Cetrorelix at different dosages

AbstractPurpose: The premature LH surge in ART programs seems to be avoided by daily administration of the GnRH-antagonist Cetrorelix during the midcycle phase in controlled ovarian hyperstimulation with hMG. The dosage necessary for sufficient suppression of the pituitary gland is not yet defined. Methods: To elucidate this question three daily dosages (3, 1, 0.5 mg) were administered and the hormone profiles obtained as well as the number of oocytes retrieved, the fertilization rate, and the consumption of HMG were compared. Results: No premature LH surge could be observed at any of the three dosages administered. Both gonadotropins were deeply suppressed. The fertilization rates of the oocytes obtained were 45.3% in the 3-mg group, 53.1% in the 1-mg group, and 67.7% in the 0.5-mg group. The average uses of hMG ampoules were 30 in the 3-mg group, 27 in the 1-mg group, and 26 in the 0.5-mg group. Conclusions: Cetrolix, 0.5 mg/day, administered during the midcycle phase of controlled ovarian hyperstimulation with hMG is enough to prevent completely the premature LH surge. Perhaps even lower dosages would be sufficient. Regarding fertilization rates and use of hMG, the lower dosage seems to be the most favorable.

Use of frozen-thawed testicular sperm for intracytoplasmic sperm injection

OBJECTIVE To determine the feasibility of using frozen-thawed testicular spermatozoa for intracytoplasmic sperm injection. DESIGN Prospective clinical study. SETTING A university hospital. PATIENT(S) One hundred seventy-five azoospermic men participating in a routine intracytoplasmic sperm injection program. INTERVENTION(S) The men underwent testicular biopsy for cryopreservation of tissue to be used in consecutive intracytoplasmic sperm injection treatment cycles. Their female partners underwent controlled ovarian hyperstimulation for conventional IVF treatment. MAIN OUTCOME MEASURE(S) Fertilization and pregnancy rates. RESULT(S) In 77% of the patients, spermatozoa could be harvested from the testis by an open testicular biopsy technique and used for intracytoplasmic sperm injection after freezing and thawing of testicular tissue. Histopathologic evaluation revealed a Sertoli cell-only pattern in 21%, maturation arrest in 60%, and hypospermatogenesis in 19% of the patients. In 2. 9% of the patients, carcinoma in situ or a germ cell tumor was detected. In all patients, viable spermatozoa could be visualized after the tissue samples were thawed. One hundred thirty-five intracytoplasmic sperm injection treatment cycles were performed, with a fertilization rate of 45% and a clinical pregnancy rate of 30% per oocyte retrieved. CONCLUSION(S) The use of frozen-thawed testicular tissue allows ovarian stimulation of the female partner to be timed and avoids cancellation of ovum pick-up when spermatozoa cannot be retrieved.

Results of cytogenetic analysis in men with severe subfertility prior to intracytoplasmic sperm injection

Intracytoplasmic sperm injection (ICSI) is increasingly becoming the treatment of choice for severe male subfertility. Cytogenetic evaluation of men with andrological subfertility reveals an increased incidence of chromosomal abnormalities when compared with the normal population. We performed chromosomal analysis on the male partners of 32 couples referred for andrological subfertility. In two of these men, constitutional chromosomal translocations were diagnosed prior to ICSI [(45,XY,t(21;22)(p11;q11) and 46,XY,t(22;Y)(p11;q12)]. Since ICSI bypasses many potential barriers of fertilization, successful pregnancy can be achieved despite the presence of severely impaired spermatozoa in a population at high risk for chromosomal aberrations. It is well known that the presence of a chromosomal aberration plays a significant role in partial or complete spermatogenic arrest. ICSI does not seem to increase the risk of fetal chromosomal abnormalities when a spermatozoon from a chromosomally normal male is used. To exclude a higher risk for spontaneous abortion and fetal chromosomal abnormalities, we advocate cytogenetic screening of males with severe male subfertility who opt for ICSI.

Mini-swim-up: A new technique of sperm preparation for intracytoplasmic sperm injection

PurposeThe male factor is nowadays one of the major problems in the treatment of infertility. New methods of assisted fertilization such as the intracytoplasmic sperm injection (ICSI) show better fertilization and pregnancy rates than classical IVF.MethodIn this study, we present a new technique of sperm preparation: the “mini-swim-up.”ConclusionThis technique, used in conjunction with the ICSI procedure, improves pregnancy and fertility rates in cases of severe oligoasthenoteratozoospermia.

Preoperative reduction of uterine fibroids in only 16 days by administration of a gonadotrophin-releasing hormone antagonist (Cetrotide)

Ten premenopausal women with symptomatic uterine fibroids confirmed by magnetic resonance imaging (MRI) were treated with four injections (s.c.) of 3 mg of the gonadotrophin-releasing hormone (GnRH) antagonist cetrorelix every 4 days, starting on the first day of cycle. On every fourth day, blood samples were drawn for the measurement of gonadotrophins and sex steroids. On the 17th day of treatment after a final MRI control, myomectomy was performed laparotomically, laparoscopically or hysteroscopically. All patients showed a deep and sustained suppression of gonadotrophins and sex steroids over the treatment time. In three patients, no change or even an increase in uterine fibroids volume was observed according to MRI, and in one patient MRI did not allow a reliable interpretation. However, six patients showed a mean reduction of 31% in fibroid size after only 16 days of hormonal treatment. In nine patients laparoscopic or hysteroscopic myomectomy could be performed, while laparotomy was necessary only in one non-responder. Preparation of the cleavage plane during surgery was easy and blood loss was minimal. Patient compliance was excellent. No side-effects occurred. The GnRH antagonist Cetrotide(R), acting as an intermediate depot preparation at a dose of 3 mg, opens up a new avenue for preoperative short term treatment in a subgroup of patients with uterine fibroids, minimizing treatment time and patient discomfort.

Prospective, randomized study to evaluate the success rates using hCG, vaginal progesterone or a combination of both for luteal phase support.

Background. A prospective study was done to compare the efficacy of luteal phase support (LPS) using either three times hCG (group I, n=77), hCG on the day of embryo transfer (ET) in combination with daily vaginal progesterone (group II, n=62) or vaginal progesterone only (group III, n=70).

Morphology in intracytoplasmic sperm injection : preliminary results

PurposeDirect intracytoplasmic sperm injection (ICSI) is a successful treatment of severe male subfertility. Conventional in vitrofertilization shows poor pregnancy rates especially in cases of severe teratozoospermia. The objective was to determine if severe morphological defects of spermatozoa in oligoasthenoteratozoospermia (OAT) have any impact on the fertilization process in ICSI and if there are any specific morphological characteristics in nonfertilized oocytes after the ICSI procedure.MethodsEjaculates and nonfertilized oocytes were investigated by electron microscopy.ConclusionsThe lack of intracytoplasmic sperm-oocyte interaction, not severe sperm defects, displays the most critical role in the fertilization process. Clinical data with fertilization rates of 66% and pregnancy rates of 23.3% confirm the fertilization capacity of severely defective spermatozoa in ICSI.

A new indication for an intracytoplasmic sperm injection procedure outside the cases of severe male factor infertility

OBJECTIVE To show the success of intracytoplasmic sperm injection (ICSI) in cases of a low number of oocytes retrieved. STUDY DESIGN 715 microinjection cycles, which were performed at our center, were analyzed retrospectively. RESULTS Within the analyzed cycles, there were 50 cycles with less than four oocytes retrieved. Twelve, 18, and 20 cases were treated with one, two, and three oocytes, respectively. The rate of metaphase II oocytes injected and subsequently fertilized, and intact oocytes was similar in the three groups. The transfer rate was not significantly different from those cases with more than three oocytes (84% vs. 94%). Therefore, the rate of fertilization failure was not higher in the low-number group. The number of embryos transferred was statistically significantly lower in the group with one and two oocytes compared to the group with three oocytes (1, and 1.31 vs. 2.27; P < 0.01) and the group of all patients (2.63; P < 0.01), as well as between the group of less than four oocytes and all patients (1.63 vs. 2.63; P < 0.01). There was no statistically significant difference between the pregnancy rates of the three groups (36.4% vs. 20% vs. 22.2%), and also no difference was found between the group with less than four oocytes and the data of all patients (22% vs. 26.9%). CONCLUSION In our opinion, these data show that ICSI guarantees a successful treatment even if only as many oocytes are present as embryos are planned to be transferred, i.e. three embryos. This has been accepted to be a new indication in our center. Therefore it should be possible to stimulate patients mildly, with e.g. clomiphene citrate, to avoid unnecessary hyperstimulation syndromes, and to lower the cost of hormonal superstimulation.

Small-diameter laparoscopy (SDL) using a microlaparoscope

AbstractPurpose: To determine the ability of new sub-2.0-mm-diameter microlaparoscopes to be used for diagnostic laparoscopy, 28 small-diameter laparoscopies (SDL) were performed during a 4-month-period. Methods: These cases were performed under general anesthesia, with immediate follow-up confirmation with conventional laparoscopic equipment. An additional 13 SDL procedures were performed under analgosedation plus local anesthesia and were well tolerated by the patients. Results: For the cases performed with conventional laparoscopic control, the visualization results were comparable in 27 of 28 procedures. In the nongeneral anesthesia SDL group, patients were highly satisfied and reported less post-procedural discomfort and minimal scar formation due to the smaller access ports. In this study, two types of microlaparoscopes were used. Conclusions: While both were adequate, the newer high-resolution microlaparoscope delivered an image much more similar to that which conventional laparoscopy and required little or no change in technique in order to obtain images. With the advent of this new endoscope technology with optics performance comparable to that of conventional laparoscopes, SDL has demonstrated to be a useful procedure for certain clinical indications.