Background. A Phase I—II trial to assess the toxicity and efficacy of a tandem high dose chemotherapy combining ifosfamide, carboplatin, and etoposide in germ cell tumors and metastatic trophoblastic disease was performed. Methods. Thirty‐nine patients, with a total of 22 testicular tumors, 9 extragonadal germ cell tumors, 3 ovarian germ cell tumors, and 5 cases of metastatic trophoblastic disease, received tandem high dose therapy combining ifosfamide (7500‐12,500 mg/m2), carboplatin (875‐1225 mg/m2), and etoposide (1000‐1250 mg/m2), followed by bone marrow reinfusion. Among the 39 patients, 33 were refractory to cisplatin‐ or carboplatin‐based regimen and the response of 37 could be evaluated; 69 cycles of this tandem high dose therapy were administered. Results. The overall response rate was 46%, including a complete response (CR) rate of 35%. Of 21 patients with testicular tumors who could be evaluated, 10 (47%) achieved a CR. No CRs were obtained in patients with refractory extragonadal germ cell tumors. Nine partial responders after the first cycle became complete responders after the second. Nine (23%) of the patients were long term survivors (> 18 months), 7 of them in continuous CR. Side effects primarily were renal toxicity and entero‐colitis. Seven patients (18%) died of therapy‐related causes. The therapeutic contribution of ifosfamide must be explored and the maximum tolerated doses of this three‐drug regimen remain to be determined. Conclusion. This tandem therapeutic regimen is able to overcome resistance to a platinum‐based regimen in highly refractory germ cell tumors and gestational trophoblastic disease and to cure a number of patients. Cancer 1995; 75:874—85.

A total of 17 couples with repetitive implantation failure after transfer of fresh or frozen-thawed embryos had half of their zygotes cultured in standard conditions and frozen at day 2 after insemination, and the other half cocultured with autologous granulosa cells and transferred at the morula or blastocyst stage at day 5 or 6 after oocyte retrieval. At the end of the culture period, supernatants of cocultures were recovered for steroid assays. Monolayers were stained for granulosa cell growth and morphological assessment. We observed that granulosa cells improve embryo development in vitro since 32 out of 60 (53%) reached the morula stage and 18 (30%) the blastocyst stage, leading to a total of 83% embryos available for transfer (compared with 3% without coculture). The ongoing pregnancy rate of these patients who were selected because they had at least three previous implantation failures, is only 5.9%, however, which is similar to the control group without coculture (6.3%). To conclude, granulosa cells improve embryo development but not the pregnancy rate after transfer of cocultured embryos in patients with multiple previous implantation failures.

Renal tubular acidosis is usually associated with chronic renal conditions and is rarely encountered in pregnancy. It may be inherited causing osteomalacia and rickets in children or acquired following autoimmune diseases or following exposure to nephrotoxic agents. It is known to worsen during pregnancy and if left untreated may cause maternal and foetal morbidity or death. We report a 28-year-old woman, gravida 3 para 2, who presented at 30 weeks gestation with lethargy, weakness and generalized myalgia. Investigation revealed severe hypokalaemia and a systemic metabolic acidosis due to proximal renal tubular acidosis. Her previous pregnancies were both complicated by foetal losses at term. Following prompt correction of her electrolyte disturbance and metabolic acidosis, she went on to deliver a healthy female infant at term. Regular evaluation up to 1 year post-partum revealed mild persistence of her hypokalaemia. At 1 year, the infant showed no signs of the disorder and is growing normally.

The prognostic value of a decrease in oestradiol-17 beta (E2) on the day after HCG injection in stimulated cycles has been related to a premature increase in plasma progesterone (P) on the day before HCG injection. This retrospective study was carried out on 363 patients who were divided into four groups. Patients in group A were given clomiphene citrate plus human menopausal gonadotrophin (HMG) to stimulate follicle growth, and they were subdivided into subgroups A1 and A2 who showed an increase or a decrease in E2 levels after HCG injection. The changes in E2 were greater than 10% of the levels on the previous day. Patients in group B were stimulated by HMG and were similarly subdivided into subgroups B1 and B2 according to their E2 levels. The number of oocytes recovered and the incidence of pregnancy was significantly higher in A2 as compared with A1, and higher but not significantly so in B2 versus B1. Moreover, in subgroups A1 and B1 the day before the decrease of E2 was marked by a significant rise in LH before the HCG injection. We suggest that oocyte recovery is deferred in these cases.

Plasma and follicular fluid (FF) hormone assays for follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), oestradiol (E2), progesterone (P), delta-4-androstenedione (A4) and testosterone (T) were performed on the day of oocyte retrieval in two groups of normo-ovulatory women enrolled in an in-vitro fertilization (IVF) programme: 24 were treated using the decapeptyl agonists DTRP6, of luteinizing hormone-releasing hormone (LHRH) in the long protocol associated with human menopausal gonadotrophin (HMG) (49 FF) and 14 were stimulated with HMG alone (33 FF). In both FF and plasma the mean concentration of P was greater, and the E2/P ratios as well as the LH levels were lower in the agonist-treated group. In this group the follicular concentration of P was greater and the E2/P ratio lower when pregnancy occurred following IVF. The hormonal modifications may be due to greater functional maturity of the granulosa cells.