Raphael Ron-El

Follow up and outcome of isthmic pregnancy located in a previous caesarean section scar

Case report A 28 year old woman was referred at seven weeks of gestation because of vaginal bleeding. Three years before she had undergone caesarean section because of breech presentation of a baby who weighed 3.8 kg at birth. The puerperium was complicated by febrile morbidity. Other than slight vaginal bleeding, there were no clinical findings. Ultrasound examination showed a pregnancy located in the i s t h c a l region (Fig. 1). Since the gestational sac was displaced anteriorly, the possibility of ectopic implantation in the previous caesarean section scar was considered. After discussion with the couple, a mutual decision. was reached to avoid any intervention at that point. It was judged that the sac, located in the isthmical region, would eventually coalesce with the uterine cavity and continue as a normal pregnancy. Repeated ultrasound examinations at 13 and 14 weeks’ gestation (Fig. 2A, B) showed a tip of the sac bulging towards the uterine cavity. However, several weeks later, the sac remained outside the uterine cavity (Fig. 2C, D). The findings and the potential dangers were discussed again, but because of the increased risk of hysterectomy associated with termination at that stage, management was unchanged. Besides diet-controlled gestational diabetes, the course of the pregnancy was uneventful. Vaginal examinations disclosed a normal cervix displaced up and laterally by the sac that was bulging into the right fornix. Caesarean delivery was planned for the 36th week of gestation, and she was admitted to the hospital two weeks before this. At 35 weeks an urgent caesarean section was performed because of acute abdominal pain. A longitudinal incision was made into the coverings of the amniotic sac and a healthy male infant weighmg 3.6 kg was born. The membranes were covered with thin fibromuscular tissue and peritoneum. The uterus was displaced to the left by the pregnancy sac and both cavities communicated at the isthmical level. There was no chorion free in the peritoneal cavity, and the placenta and its vessels were visible through transparent thin uterine wall and peritoneum. The placenta was of normal size, attached firmly to the low anterior aspect of the sac, and was

Intracytoplasmic injection of fresh and cryopreserved testicular spermatozoa in patients with nonobstructive azoospermia—a comparative study

OBJECTIVE To compare the outcome of intracytoplasmic sperm injection (ICSI) with fresh and frozen-thawed testicular spermatozoa in patients with nonobstructive azoospermia. DESIGN Retrospective analysis of consecutive ICSI cycles. SETTING In Vitro Fertilization Unit, Assaf Harofeh Medical Center. PATIENT(S) Eighteen with nonobstructive azoospermia in whom testicular sperm was found after testicular sperm extraction. INTERVENTION(S) Testicular sperm retrieval, cryopreservation, and ICSI with fresh or frozen-thawed testicular spermatozoa. MAIN OUTCOME MEASURE(S) Two-pronuclear fertilization; embryo cleavage rates, mean number of embryos transferred per cycle, and their relative quality, embryo implantation, clinical pregnancy, and ongoing pregnancy rates (PRs) per ET. RESULT(S) No statistically significant differences were noted in all parameters examined between ICSI cycles with fresh or cryopreserved testicular spermatozoa from the same nine patients and comparing all ICSI cycles performed; with fresh (25 cycles) and thawed (14 cycles) testicular spermatozoa, respectively: two-pronuclear fertilization, 47% versus 44%; embryo cleavage rates, 94% versus 89%; implantation rates, 9% versus 11%; and clinical PR, 26% versus 27%. The delivery or ongoing PR using fresh sperm was better (21% versus 9%), but the difference did not reach statistical significance. The cumulative clinical PRs and ongoing PRs per testicular sperm extraction procedure were 36% and 24%, respectively. CONCLUSION(S) Testicular sperm cryopreservation using a simple freezing protocol is promising in patients with nonobstructive azoospermia augmenting the overall success achieved after surgical sperm retrieval.

Delayed fertilization and poor embryonic development associated with impaired semen quality

Delayed fertilization is common in cycles with immature oocytes. This phenomenon was observed in 42 of 423 with mature oocytes. Of the 42 cycles, 16 were excluded because of the presence of sperm autoantibodies. Sperm parameters of the remaining 26 (6.1%) cycles (group A) were compared with those in cycles with no fertilization at all (group B) and those in the control group (group C). The percentage of normal forms was 15% in group B and 24% in group A compared with 51% in group C. Fertilization rates were 32% in group A compared with 81% in group C. The incidence of poor embryonic morphology was 82% in group A compared with 29% in group C. Delayed fertilization and poor embryonic morphology associated with impaired sperm quality is of clinical and prognostic importance.

Meiotic Arrest In Vitro by Phosphodiesterase 3-Inhibitor Enhances Maturation Capacity of Human Oocytes and Allows Subsequent Embryonic Development

Abstract Controlling nuclear maturation during oocyte culture might improve nuclear-cytoplasmic maturation synchrony. We aimed to evaluate the quality of in vitro-matured, germinal vesicle (GV)-stage human oocytes following a prematuration culture (PMC) with a meiotic arrester, phosphodiesterase 3-inhibitor (PDE3-I). Follicles (diameter, 6–12 mm) were retrieved 34–36 h post-hCG administration from informed, consenting patients who had undergone controlled ovarian stimulation. Cumulus-enclosed oocytes (CEOs) presenting moderate expansion or full compaction were placed in PMC with the PDE3-I, Org9935, for 24 or 48 h. Subsequently, oocytes were removed from PMC, denuded of cumulus cells, matured in vitro, and fertilized, and the resulting embryos were cultured. In the presence of PDE3-I, approximately 98% of the oocytes were arrested at the GV stage. Following PDE3-I removal, oocytes acquired a higher maturation rate than oocytes that were immediately denuded of cumulus cells after retrieval and in vitro matured (67% vs. 46%, P = 0.01). In controls, immature CEOs retrieved with moderate expansion reached higher maturation rates compared to fully compacted CEOs, but in PMC groups, high values of maturation were achieved for both morphological classes of CEOs. No effect of PMC on fertilization was observed. A 24-h PMC period proved to be the most effective in preserving embryonic integrity. Similar proportions of nuclear abnormalities were observed in embryos of all in vitro groups. In summary, PMC with the specific PDE3-I had a beneficial effect on human CEOs by enhancing maturation, benefiting mainly the fully compacted CEOs. This resulted in an increased yield of mature oocytes available for insemination without compromising embryonic development. These results suggest that applying an inhibitor to control the rate of nuclear maturity by regulating intraoocyte PDE3 activity may allow the synchronization of nuclear and ooplasmic maturation.

Hypercoagulable Thrombophilic Defects and Hyperhomocysteinemia in Patients with Recurrent Pregnancy Loss

PROBLEM: Placental perfusion may be compromised by increased thrombosis that leads to pregnancy complications and recurrent pregnancy loss (RPL). Since heritable thrombophilic defects and hyperhomocysteinemia are associated with increased thrombosis, their prevalence was evaluated in RPL patients with special emphasis on combinations of the above pathologies.
 METHODS OF STUDY: Evaluation of the prevalence of heritable thrombophilic defects (protein S, protein C, anti‐thrombin III deficiency, and the mutations for factor V Leiden, methylenetetrahydrofolate reductase [MTHFR], and prothrombin gene), hyperhomocysteinemia, and combinations of these pathologies in 36 non‐pregnant recurrent aborters compared with 40 parous women.
 RESULTS: We found a relatively high prevalence of deficiencies of plasma coagulation proteins in RPL patients compared with the controls. A non‐significant different increase in factor V Leiden mutation was detected (6/36 [16%] compared with 2/40 [5%] in the control group, P=0.14]. Hyperhomocysteinemia was found in 31% of the RPL patients. MTHFR mutation homozygosity was found in 6/36 (16%) of the aborting patients. Combinations of hyperhomocysteinemia and MTHFR mutation were found in three patients, with folate deficiency in two patients, and with B12 deficiency in three.
 CONCLUSIONS: Combinations of gene mutations, plasma protein deficiencies, and hyperhomocysteinemia, which are associated with an increased thrombotic risk, are more common in RPL patients compared with controls. Large‐scale prevalence studies are needed in order to draw conclusions as to the causative relation of such a condition and RPL.

Male genital mycoplasmas and Chlamydia trachomatis culture: its relationship with accessory gland function, sperm quality, and autoimmunity

To study the effect of mycoplasmas and Chlamydia trachomatis infection on semen quality, these microorganisms were cultured from the semen and anterior urethra respectively, in a group of 175 infertile men suspected of a silent genital infection with a poor postcoital test. Chlamydia infection, but not mycoplasmas, was parodoxically more frequent in the apparently normal than oligotetratoasthenozoospermia patients. Mycoplasmas male infection, but not chlamydia, was more frequent in cases with female, mechanical, and/or organic infertility factors. Infection was unrelated to the accessory gland evaluation or sperm variables. However, seminal antisperm antibody activity was significantly increased in cases with any positive culture. By this local antibody increase, chlamydia and mycoplasmas may significantly reduce sperm egg penetration ability.

Outcome of assisted reproductive technology in women over the age of 41

OBJECTIVE To analyze the results of ongoing pregnancies and deliveries after assisted reproductive technology (ART) in women aged >/=41 years, stratified by year of age. DESIGN Retrospective study. SETTING University hospital, IVF unit. PATIENT(S) A total of 431 IVF and intracytoplasmic sperm injection (ICSI) cycles were initiated in women >/=41 years of age. INTERVENTION(S) Medical files of ART patients and pregnancy outcomes were reviewed. MAIN OUTCOME MEASURE(S) Oocytes retrieved, embryos developed, and clinical pregnancy and delivery rates. RESULT(S) Of the 431 started cycles, 376 (87%) reached the oocyte retrieval stage. The mean number of oocytes aspirated per patient was 5.4 +/- 0.9 and 6.7 +/- 1.2 in the IVF and ICSI cycles, respectively, and the number of embryos obtained was 2.3 +/- 1.3 and 2.8 +/- 1.6 in the IVF and ICSI cycles, respectively. The number of transferable embryos was 2.0 +/- 1.2 and 2.5 +/- 0.8. The pregnancy rate per oocyte pickup (OPU) was 12.4%; however, the delivery rate per OPU was 4.5%. The mean delivery rate per OPU among women aged 41-43 years was 2%-7%. There were no deliveries aged >/=44 years and no pregnancies at the age of 45 years. The pregnancy and delivery rates of the ICSI and IVF patients were similar after stratification by age. CONCLUSION(S) In our studies, ART performed with homologous oocytes, whether by IVF or ICSI, yielded no clinical pregnancies among women aged >/=45 years and no deliveries aged >/=44 years. The mean delivery rate per oocyte retrieval among women aged 41-43 years varied between 2% and 7%.

Ovarian pregnancy: A report of twenty cases in one institution

A series of 20 cases of primary ovarian pregnancy that were diagnosed and treated in one institution is reported. The prevalence rate of 1:3600 deliveries seems to be increasing in past years and comprises 3.3% of all extrauterine pregnancies. Clinical presentation, possible pathogenesis, diagnostic steps, preferred management, and future fertility are detailed. Inasmuch as all our 18 fertile patients used an intrauterine contraceptive device before the operation, special emphasis is made on the controversial relationship between use of intrauterine contraceptive devices and ovarian pregnancy.

Pregnancy rate and ovarian hyperstimulation after luteal human chorionic gonadotropin in in vitro fertilization stimulated with gonadotropin-releasing hormone analog and menotropins.

The value of luteal phase supplementation with human chorionic gonadotropin (hCG) was assessed after a combined protocol of ovarian stimulation, using a long acting gonadotropin releasing hormone analog (GnRH-a) and human menopausal gonadotropins (hMG), in a randomized prospective study of 36 consecutive cycles in an in vitro fertilization (IVF) program. The patients were allocated on the transfer day to either luteal phase supplementation with hCG (Group A, n = 18) or none (Group B, n = 18). Nine patients of Group A conceived as compared with 3 in Group B. Five patients, all in Group A, developed ovarian hyperstimulation syndrome (OHSS) (3 moderate and 2 severe forms). Analysis of the hormonal profiles disclosed similar progesterone (P), estradiol (E2), and E2/P ratio up to the 6th post ovum pick-up day. Then, E2 and mainly P levels decreased only in Group B resulting in a rising E2/P ratio. These findings stress the importance of luteal support in IVF cycles treated with GnRH-a. In light of the increased risk of OHSS among hCG treated patients, further studies are needed to assess the optimal preparation needed.

Ovarian hyperstimulation syndrome following D-Trp-6 luteinizing hormone-releasing hormone microcapsules and menotropin for in vitro fertilization.

In 143 cycles of in vitro fertilization the ovarian hyperstimulation syndrome (OHSS) occurred in 12 (8.4%) cycles. Six were in the moderate form and 6 severe. Ovarian stimulation by menotropins was preceded by induction of hypopituitary hypogonadism using D-Trp6-LH-RH microcapsules. The OHSS cycles are characterized by improved ovarian response expressed by the increased serum levels of estradiol, number of follicles, oocytes, embryos and pregnancy rate as compared to cycles with no OHSS. All patients recovered uneventfully. The follicular puncture did not have the suggested protective effect against OHSS. It is suggested that the substantial incidence of OHSS is probably related to the excessive ovarian stimulation not interrupted by early luteinization which is practically abolished by this protocol. The role of the given luteal hCG doses in the genesis of OHSS is questioned.