Santiago L. Padilla

Use of the flare-up protocol with high dose human follicle stimulating hormone and human menopausal gonadotropins for in vitro fertilization in poor responders

OBJECTIVE To analyze the effect of high dose human FSH in combination with hMG with a flare-up leuprolide acetate (LA) protocol in patients undergoing IVF at risk for a poor response. DESIGN Prospective. SETTING Free-standing ambulatory IVF center. PATIENTS Two hundred eighty-four patients underwent a LA screening test for IVF. Patients with a lack of flare response were considered at risk for a poor response and underwent ovarian stimulation with the flare-up LA protocol in combination with high dose human FSH and hMG. RESULTS The poor responder group was compared with the good responders on the flare-up LA protocol and to patients undergoing ovulation induction with a luteal phase LA protocol. There were 53 poor responder flare-up LA cycles, 177 good responder flare-up LA cycles, and 54 luteal phase LA cycles. The cancellation rate was higher in poor flare-up LA responders (11.3 percent) compared with good flare-up LA responders (1.1 percent) and luteal phase LA cycles (1.8 percent). Peak E2 levels, number of oocytes, and number of embryos were significantly higher in the good flare-up LA responders. Fertilization rate was similar in all groups. Ongoing pregnancy rate per retrieval was 28 percent in good responders, 29 percent in poor responders, and 33 percent in luteal phase LA patients. Only one patient (0.4 percent) was hospitalized for severe ovarian hyperstimulation. CONCLUSION The flare-up protocol with high-dose human FSH and hMG is a very good alternative for patients who are at high risk for a poor response. Although peak E2 and number of oocytes were significantly lower in this group, the patients who responded had the same fertilization and pregnancy rate as the good responders. Cancellation rate remains high in poor responders.

The value of oocyte reinsemination in human in vitro fertilization

The value of oocyte reinsemination in human in vitro fertilization (IVF) was evaluated in this study. Two groups of 25 cycles each were studied. In group 1 cycles, insemination of mature/questionably mature oocytes (judged by cumulus and corona cell appearance) at 6.5 hours postcollection yielded a fertilization rate of 42.3%. This value was significantly lower than that obtained with reinsemination (70.8%). In group 2, questionably mature oocytes were treated as immature and inseminated 24 to 30 hours postcollection. The fertilization rate of mature eggs in group 2 was 68.2%, with a reinsemination success rate of 40%. Triploidy rates and cleavage rates of mature eggs, fertilized either at initial insemination or reinsemination and of fertilized immature eggs, were similar within group 1 and group 2 cycles. In group 1, two pregnancies resulted from transfer of embryos arising solely from successful reinsemination, with one infant delivered. These results indicate that reinsemination offers a useful adjunct for IVF in cases where fertilization failure occurs.

The efficacy of bromocriptine in patients with ovulatory dysfunction and normoprolactinemic galactorrhea

The response to bromocriptine therapy of 12 infertile women with ovulatory dysfunction and euprolactinemic galactorrhea was studied. Four of the subjects had anovulation, four had oligo-ovulation, and four had delayed ovulation. Serum PRL levels in all 12 subjects were less than 20 ng/ml. Normal ovulation occurred at least once in all of the patients on bromocriptine therapy and in 38 of 41 (92%) of the cycles. Seven patients (58%) conceived promptly with bromocriptine therapy, and all subjects had cessation of galactorrhea within 1 month of the onset of therapy. The seven pregnancies included five normal term vaginal deliveries, one premature vaginal delivery, and one tubal pregnancy. The results of this study should be considered preliminary but suggest that the presence of euprolactinemic galactorrhea in patients with ovulatory dysfunction may still represent a covert disorder of PRL physiologic factors. The prompt correction of these ovulation disturbances gives supporting evidence for this hypothesis and suggests that a short trial of bromocriptine therapy may be warranted after minimal blood sampling. The differential outcome between our group of patients produces further evidence that variable mechanisms may be operative.

Comparison of synthetic serum substitute and fetal cord serum as media supplements for in vitro fertilization: A prospective, randomized study

OBJECTIVE To compare the value of synthetic serum substitute and fetal cord serum (FCS) as protein supplements in the media used for IVF. DESIGN Prospective, randomized study of 45 patients undergoing IVF. SETTING Private infertility practice. INTERVENTION(S) The protein supplement for use in IVF medium was randomized prospectively to synthetic serum substitute or FCS. MAIN OUTCOME MEASURE(S) Oocyte fertilization rate, incidence of embryo arrest, number of embryos transferred, ongoing pregnancy rate, and implantation rate were assessed. RESULT(S) There was no significant difference in the fertilization rate, incidence of embryo arrest, number of embryos transferred, ongoing pregnancy rate, and implantation rate. CONCLUSION(S) Synthetic serum substitute is a better alternative to FCS as a protein supplement for IVF because of its availability and cost effectiveness. Synthetic serum substitute can be used in culture medium for sperm washing, insemination, culture, and transfer translating to decreased technician time without a significant difference in fertilization, pregnancy, or implantation rate.

Laparoscopically assisted gamete intrafallopian transfer with local anesthesia and intravenous sedation

OBJECTIVE To determine the length of procedure, length of recovery, patient tolerance, complications, and pregnancy rate (PR) of laparoscopically assisted GIFT performed during local anesthesia with i.v. sedation. DESIGN A retrospective study. SETTING Freestanding private ambulatory surgical center. PATIENTS Thirty-one consecutive couples with infertility. INTERVENTIONS Laparoscopically assisted GIFT during local anesthesia with i.v. sedation. MAIN OUTCOME MEASURES Surgery time, recovery time, patient tolerance, PR, miscarriage rate, and complications. RESULTS Cannulation of at least one fallopian tube was achieved successfully in all patients. The average surgery time was 64 +/- 12 minutes (mean +/- SD). The average recovery time was 92 +/- 30 minutes. The PR was 39% with an ongoing PR of 32%. There were no intraoperative or postoperative complications. CONCLUSION Local anesthesia with IV sedation for GIFT using a two-puncture laparoscopic technique was well tolerated by the patients. Our ongoing PR of 32% compares very favorably with other series using general anesthesia.

Effects of charcoal-extracted serum as a growth medium supplement on in vitro development of mouse embryos

Two-cell mouse embryos (N=952) were cultured in modified Hams F-10 medium supplemented with 15% charcoal-extracted serum or 15% nonextracted serum from 17 patients. Each sample was assayed independently and all experiments run in duplicate. Ten nonextracted samples inhibited development to the blastocyst stage compared to controls in F-10 alone. Charcoal extraction significantly improved (P<0.05) development compared to nonextracted serum in eight of these samples. Seven samples supported development and no difference was noted between F-10 alone and extracted and nonextracted serum-supplemented media in this group. In conclusion, charcoal extraction significantly reversed the “embryotoxic” effects of some sera in the two-cell mouse embryo model.

Unruptured pregnancy in a heterotopic fallopian tube: Evidence for transperitoneal sperm migration

A case of an unruptured pregnancy in a heterotopic left fallopian tube isolated from a unicornuate uterus with a normal contralateral tube and ovary is presented. The corpus luteum of pregnancy was in the left ovary. This case provides supportive evidence for transperitoneal sperm migration.

Transurethral ultrasound-guided oocyto retrieval for in vitro fertilization

Thirty-nine follicular aspirations for in vitro fertilization were performed in 30 patients. Oocyte retrieval was performed by laparoscopy in 21 cases and ultrasound-guided transurethral aspiration in 18 cases. All procedures were performed by the same ovarian stimulation protocol and the same aspirating needle. In the laparoscopy group 150 oocytes were recovered from 177 follicles aspirated (85%). The fertilization rate was 69% (104/150) and cleavage rate, excluding triploidy, was 82% (85/104) for oocytes obtained by laparoscopy. Five clinical pregnancies occurred in the laparoscopy group for a pregnancy rate of 24% per cycle and 25% per transfer. In the transurethral ultrasound-guided group 77 oocytes were recovered from 103 follicles aspirated (75%). The fertilization rate was 79% (61/77) and cleavage rate, excluding triploidy, was 90% (55/61). Three pregnancies occurred for a pregnancy rate of 17% per cycle and 18% per transfer. None of these differences were statistically significant. Transurethral ultrasound-guided oocyte retrieval is a feasible alternative to laparoscopy for in vitro fertilization.

Plasminogen in peritoneal fluid: A possible nonsteroidal indicator of ovulation

Plasminogen levels in peritoneal fluid were evaluated in 40 fertile women with regular ovulatory cycles. Fifteen samples were obtained before ovulation and 25 samples after ovulation. Plasminogen content and concentration in postovulatory peritoneal fluid was 0.84 +/- 0.10 mg and 6.1 +/- 0.57 mg/dl, respectively. These values were significantly higher than in the preovulatory peritoneal fluid, which were 0.36 +/- 0.12 mg (P less than 0.005) and 3.5 +/- 0.33 mg/dl, (P less than 0.001), respectively. Estradiol and progesterone (P) concentrations in peritoneal fluid were significantly higher after ovulation (P less than 0.05 and P less than 0.01, respectively). P concentration in serum and peritoneal fluid showed a linear correlation (P less than 0.05). Peritoneal fluid plasminogen is significantly elevated after ovulation and may be a nonsteroidal marker for follicular rupture and oocyte extrusion.

Possible parthenogenesis with in vitro fertilization subsequent to ovarian cystic teratomas

A possible two-cell parthenogenetic embryo aspirated at oocyte retrieval for in vitro fertilization in a woman with a history of bilateral cystic teratomas is reported.