Jacob Ashkenazi

Ovarian cyst formation: a complication of gonadotropin-releasing hormone agonist therapy.

Since gonadotropin-releasing hormone (GnRH) analogs were introduced into clinical therapeutic use, several side effects directly related to the hypoestrogenic state have been reported. The authors have encountered a rather infrequent complication, namely ovarian cystic formations, when using these compounds for selected in vitro fertilization and embryo transfer (IVF-ET) cases. In 7 of 24 patients with Decapeptyl (D-Trp6-luteinizing hormone-releasing hormone [LH-RH], Ferring, Kiel, FRG) treatment, and in 5 of 22 patients treated with Buserelin (Superfact, Hoechst A.G., Frankfurt, FRG), solitary ovarian cysts developed during the down-regulation phase. Their growth did not change during ovulation induction with menotropins. Although the mechanism of ovarian cyst formation during GnRH agonist treatment is not clear, their presence does not appear to interfere with the fertility of these women.

Transvaginal ultrasonic needle-guided aspiration of endometriotic cysts before ovulation induction for in vitro fertilization

Controversy still exists concerning the optimal treatment of endometriomata in endometriosis and its related infertility. Forty-one women with endometriomata who failed to conceive during previous in vitro fertilization and embryo transfer (IVF-ET) cycles (protocol A) were readmitted for ovum pickup following transvaginal ultrasonic needle-guided aspiration of the endometriomata (protocol B). Following aspiration a significantly higher number of oocytes was recovered (P<0.0006); subsequently, more embryos were transferred, and significantly higher clinical pregnancy rates per cycle (P<0.0001) were achieved. This difference may be directly related to the reduction of extensive ectopic endometrial tissue (endometriomata) with improved ovarian response, follicular accessibility, and most probably, improved oocyte quality.

Age and pregnancy rates in in vitro fertilization

The influence of women[s age on the results of in vitro fertilization (IVF) was analyzed in 1801 women undergoing the procedure. Advancing age was found to be related to significant reduced success rates from an average of 30.1% per transfer below the age of 36 years to 15.9% per transfer at 37 years or more (P<0.001). The decrease was related to a reduction in oocyte production (five at 25 years or less, four below the age of 40 years, three at 40 years or more, and two in the 43 to 47-year group) and probably-due to reduced implantation. It is concluded that a womans age must be considered an important prognostic factor when IVF is suggested.

The impact of high progesterone levels in the follicular phase of in vitro fertilization (IVF) cycles: A comparative study

Estrogen (E2) and plasma progesterone (P4) levels are valuable parameters for follicular development in in vitro fertilization (IVF) cycles. Furthermore, the progesterone concentration prior to, during, and following human chorionic gonadotropin (hCG) administration is an important marker for the detection of early luteinization and premature ovulation. The pattern of hormonal profile in relation to the number of oocytes retrieved, fertilized, and cleaved and the fate of the pregnancies achieved were compared in three groups of patients treated by the same protocol. Group I included 22 women who conceived with high progesterone levels on day hCG+1 (P4>2.5 ng/ml). Group II included 43 women who conceived with low P4 values (P4<2.5 ng/ml), while group III included 46 patients in whom no pregnancies occurred. A significant decrease in fertilization, cleavage, and pregnancy rates was observed in patients with high progesterone levels on day hCG+1, compared to those with normal levels. Nevertheless, it is suggested that cycles with high P4 levels in the preovulatory phase should not be canceled, as a fair chance for pregnancy still exists.

The value of hysteroscopy in elderly women prior to in vitro fertilization-embryo transfer (IVF-ET): A comparative study

Two hundred eighty-four hysteroscopies were performed in 312 (91%) candidates for in vitro fertilization and embryo transfer (IVF-ET) who were divided into two groups. Group I consisted of elderly women over 40 years, and group II of women below this age. Although visualization revealed uterine abnormalities in 29.9% of all patients, abnormal findings were significantly increased in the former group in comparison to the latter (P<0.001). This difference was attributed mainly to uterine rather than cervical pathology. Furthermore, in elderly women agerelated uterine pathology such as submucous myomata, endometrial hyperplasia, and polyps were more prominent, while in younger patients other uterine lesions such as adhesions and tubal ostia occlusion were more common. Moreover, treatment prior to IVF-ET resulted in 7 clinical pregnancies (8.9%) in group I and in 41 clinical pregnancies (19.9%) in group II, all of which failed in one to three cycles previously. It seems that hysteroscopic evaluation may reduce the IVF-ET failure rate due to intrauterine abnormalities in elderly as well as young patients, thus it becomes an absolute prerequisite for all patients scheduled for an IVF program.

The impact of embryo quality on pregnancy outcome in elderly women undergoing in vitro fertilization-embryo transfer (IVF-ET)

Most IVF-ET units limit the procedure to women below age 38. Nevertheless, demands for infertility treatment, including IVF therapy, are more frequent nowadays. We compared 46 cycles for ovulation induction for IVF in 46 women aged 40 or more (Group I) to 51 induced cycles for this procedure in younger women of mean age 30.2 years (Group II). Cancellation rates due to early luteinization or ovulation were significantly higher in group I than in group II (28.2 and 17.6%, respectively) (P<0.001). Also, significantly higher abortion rates were observed in older women (62.5%), in comparison to the younger control group, (25%), (P<0.001). It is suggested that the high abortion rate considered to be due to genetic factors in older women, may possibly also be due to the aging uterine environment. Furthermore, while embryos with fragmentations may often produce clinical pregnancies in the young, the aging uterus in the elderly woman does not encourage the development of clinical pregnancies in such embryos. Consequently the higher abortion rate in the elderly woman.

Very early pregnancy wastage in in vitro fertilization and embryo transfer (IVF-ET)

The occurrence and incidence of early pregnancy wastage in an in vitro fertilization and embryo transfer (IVF-ET) program have been studied in 750 patients. In 297 (39.6%) a pregnancy was diagnosed; of these, 14.8% were biochemical and 24.8%, clinical pregnancies. In the latter group 23.6% aborted, while 75.8% had clinical ongoing pregnancies. The mean embryo quality score of the biochemical pregnancy group was similar to that of the clinical ongoing pregnancy group but statistically different from that of the clinical abortion group (P<0.005). Furthermore, the clinical ongoing pregnancy rate in women with previous biochemical pregnancy was 24.7%, a significantly higher percentage compared to clinical ongoing pregnancies achieved in IVF-ET cycles (P<0.05). It is possible that biochemical pregnancy does not represent an index for infertility but rather an intact stage of reproduction leading toward implantation. The high clinical pregnancy rate in subsequent cycles may probably serve as an encouraging sign or a marker for future clinical pregnancy.

The impact of spermatic vein ligation on the male factor in in vitro fertilization-embryo transfer and its relation to testosterone levels before and after operation

Criteria for improved semen quality after varicocele operations are not clear, as they do not express sperm fertilization capacity, its most important qualification. Twenty-two couples, 12 with mechanical female infertility (group I) and 10 with normal female fertility (group II), in whom the husband had subfertile semen in the presence of varicocele, and who had failed preoperative in vitro fertilization-embryo transfer (IVF-ET) attempts, were readmitted for the IVF-ET procedure following the repair of varicocele. In group I, a 20% pregnancy rate was achieved after the operation, while no pregnancies occurred before surgery. In group II, four pregnancies (40%) were achieved after operation. Plasma testosterone (T) levels demonstrated a significant increase in 50% of the patients in both groups after surgery, resulting in a concurrent improved fertilization, cleavage, and pregnancy rates.

The vaginal contraceptive diaphragm and the condom ― a reevaluation and comparison of two barrier methods with the rhythm method

The use-effectiveness and continuation rates of two barrier methods of contraception, the diaphragm and condom, were studied during a two-year follow-up in a group of 85 and 98 women, respectively. All were highly motivated. Results were compared to a group of 64 women using the periodic abstinence or rhythm method, i.e. not using any contraceptive. The patients selected the method of contraception they preferred and were instructed in their proper use. Results showed good continuation rates in the groups using a diaphragm and the condom for 2 years, for a total follow-up of 5570 cycles. Pregnancy rate after 24 months of use, as calculated by Pearls formula, was 2.48 for the diaphragm, 3.21 for the condom, and 5.19 in the rhythm group. No serious side effects or complications occurred in either group. The study demonstrated a fair acceptability and use-effectiveness for barrier contraceptive. We suggest that these harmless and complication-free methods may still be reasonable alternatives for the modern methods, the pill and the IUD.

Successful management and outcome of heterotopic triplet in vitro fertilization (IVF) gestation: twin tubal and surviving intrauterine pregnancy.

The question whether excessive androgen secretion by the adrenal gland might be the result of a primary disorder, or is a secondary event produced by the ovarian hormonal milieu, remains unsettled. There is some evidence suggesting that the adrenal defect might be caused by a variety of steroids, but in particular estrogens, which have the capacity of inhibiting 3t3-ol activity (7). Several studies have shown a correlation between estrogen concentrations and levels of adrenal androgens (5,6). On the other hand, it has been demonstrated that patients with PCOD may have a subtle degree of 313-ol deficiency (3). Our patient demonstrated only partial suppression of androstenedione and testosterone following dexamethasone administration. While this might indicate a possible ovarian origin, enhanced DHEA conversion in peripheral tissue as a source for these androgens cannot be excluded (4). The fact that the adrenal disorder is easily correctable with dexamethasone implies that diagnostic effort to define the exact enzymatic defects should be attempted in all women with unexplained sterility, in particular those who are due to undergo IVF-ET. It should be emphasized that late-onset adrenal hyperplasia might present itself in various clinical forms or even remain asymptomatic and attempts to achieve ovulation with various hormonal treatments might be potentially hazardous (overstimulation syndrome) or even inefficient therapy (low responders). Those cases might benefit from low-dose dexamethasone if an adrenal biosynthetic defect is found. Obviously this might improve ovulation induction protocols and possibly the conception rate, which is presently quite low for IVF-ET in these particular cases.