Khalid M. Sultan

Unsuspected Chlamydia trachomatis infection and in vitro fertilization outcome.

OBJECTIVE Chlamydia trachomatis infections of the female genital tract, although a major cause of infertility, are often asymptomatic and undetected. Since many infertile women now seek in vitro fertilization, a procedure whereby fertilization and embryo implantation are precisely timed, we sought to determine the relation between an unsuspected C. trachomatis infection and the ability of embryos to implant and develop after their transfer to the uterus. STUDY DESIGN At the time of oocyte aspiration, endocervical samples were obtained from 216 women and assayed by enzyme-linked immunoassay for immunoglobulin A antibodies to C. trachomatis structural membrane components and to recombinant C. trachomatis heat shock protein. The presence of C. trachomatis in the cervices was assessed by the polymerase chain reaction. The outcome of each in vitro fertilization cycle was then ascertained. RESULTS Oocytes from 198 (91.7%) of the women were fertilized in vitro and subsequently transferred to the uterus. Term deliveries of healthy infants occurred after 68 (34.3%) of these transfers. Cervical immunoglobulin A antibodies to chlamydial heat shock protein were detected in 5 (7.3%) of the women with term births, and 1 (1.5%) also had immunoglobulin A antibody to chlamydial structural components; 3 (4.4%) were positive by the polymerase chain reaction for C. trachomatis. In contrast, among the 130 women whose embryo transfers did not result in an ongoing pregnancy, 36 (27.7%) had cervical antiheat shock protein immunoglobulin A (p = 0.0007) and 24 (18.5%) had antichlamydial structural component immunoglobulin A (p = 0.0002); 15 (11.5%) of these women had positive results of polymerase chain reaction for C. trachomatis. The majority of women with cervical antibodies to chlamydial structural antigens were also positive for antibody to heat shock protein. However, only 35% of the women with antibodies to heat shock protein were also positive for the other chlamydial antibodies. C. trachomatis was detected by polymerase chain reaction in 29.2% of women with anti-C. trachomatis antibodies and 7.8% of women with anti-heat shock protein antibodies. Women positive for antichlamydial immunoglobulin A were more likely to be undergoing a repeat in vitro fertilization cycle than were women who were antibody negative (p = 0.007). CONCLUSION Unsuspected C. trachomatis infection or reactivation of an immune response to the C. trachomatis heat shock protein may induce an inflammatory reaction in the uterus that impairs embryo implantation and/or facilitates immune rejection after uterine transfer of in vitro fertilized embryos.

Sperm quality may adversely affect the chromosome constitution of embryos that result from intracytoplasmic sperm injection.

OBJECTIVE To determine whether the high rate of chromosomal abnormalities in the embryos of an infertile couple were caused by a paternal factor that may have involved the sperm centriole. DESIGN Case report. SETTING Private IVF program. PATIENT(S) An infertile couple who underwent IVF-ET because of severe male factor infertility and endometriosis. INTERVENTION(S) Preimplantation genetic diagnosis of chromosomal abnormalities in embryos derived from two cycles of ICSI in which the husbands sperm was used and one in which donor sperm was used. MAIN OUTCOME MEASURE(S) Preimplantation genetic diagnosis with fluorescence in situ hybridization using probes for chromosomes X, Y, 13, 16, 18, and 21, and determination of hCG levels. RESULT(S) Most of the embryos derived from the cycles in which the husbands sperm was used were chromosomally abnormal (82%), whereas all the embryos derived from the cycle in which donor sperm was used were chromosomally normal. The cycle in which donor sperm was used resulted in an ongoing pregnancy. CONCLUSION(S) Paternal factors, which most likely derive from the centrosome, can contribute to numerical chromosomal abnormalities, which in turn may predispose to implantation failure.

Ectopic pregnancies after in vitro fertilization and embryo transfer.

ObjectiveOur objective was to analyze the risk factors, stimulation characteristics, and future fecundity of patients with ectopic pregnancies after in vitro fertilization (IVF).MethodsWe retrospectively evaluated all cases of ectopic pregnancy occurring between January 1989 and March 1993 (Cornell series 1 to 17). A case-control group of intrauterine pregnancies was used for comparison of the stimulation and transfer characteristics.ResultsTwenty-seven of 1123 pregnancies (2.4%) were ectopic, following 2812 fresh IVF embryo transfers, while 8 of 105 pregnancies (7.6%) were ectopic, following 405 frozen-thawed embryo transfers. Tubal factor was the cause of infertility in the majority (85.7%) of ectopic pregnancies. No difference was found between the ectopics and the matched controls in stimulation and transfer characteristics. Thirty ectopic pregnancies were ampullary, two were interstitial, two were cervical, and one was heterotopic. Twenty of the patients subsequently underwent 29 IVF attempts, with a pregnancy rate of 41.4% per transfer.ConclusionsEctopic pregnancy after IVF appears to be related to preexisting tubal pathology; embryo transfer of cryopreserved thawed embryos in a natural cycle may result in a higher ectopic rate in these patients; in subsequent IVF cycles the intrauterine pregnancy rate of these patients is not decreased.

Pregnancies from single normal embryo transfer in women older than 40 years

The aim of this retrospective study was to determine the pregnancy rate from the transfer of single genetically normal embryos in patients of advanced reproductive age. The study group included 23 patients (mean age 42.2 +/- 1.3 years) who underwent 27 in-vitro fertilization (IVF) cycles in which preimplantation genetic diagnosis (PGD) was carried out on single blastomeres from day 3 embryos. The control group included 54 patients (mean age 43.3 +/-1.9 years) who underwent 69 cycles of IVF without PGD. Ovarian stimulation in all patients consisted of follicular phase leuprolide acetate administration, followed by ovulation induction with gonadotrophins. The mean number of biopsied embryos was 5.6 +/- 0.5. No embryo transfer occurred in six patients (10 cycles) because all embryos biopsied were abnormal. Seventeen patients (17 cycles) each had one genetically normal embryo transferred resulting in six on-going clinical pregnancies (35% per embryo transfer cycle). The mean number of embryos transferred in the control group was 4.0 +/- 0.8. Nineteen clinical pregnancies were obtained in 69 transfer cycles in the control group (28% per embryo transfer cycle). The transfer of a single normal embryo in patients of advanced reproductive age can lead to acceptable pregnancy rates. Aneuploidy appears to be a major cause of reproductive failure in this group of patients.

Viable term pregnancy despite “subluteal” serum progesterone levels in the first trimester

This is a report of a 34-year-old patient with a 3-year history of unexplained infertility, who conceived after IVF-ET. Her serum P levels were < 2.0 ng/mL (conversion factor to SI unit, 3.180) between 5 and 6 weeks of gestation. She subsequently delivered a viable infant at term.

A novel technique for cervical cannulation during hysterosalpingography

In this series 40 patients presenting for HSG had cervical stenosis impeding cervical cannulation with an acorn tip catheter. Successful cervical cannulation was obtained in all instances, using a modified tom cat catheter as described. Successful visualization of the uterine cavity was achieved in all 40 patients.

Pregnancy Rate from the Transfer of a Single Normal Embryo in Women of Advanced Reproductive Age Undergoing PGD for Determination of Aneuploidy

MII n 5 203 46 (22.7%) 41 (20.2%) 40 (19.7%) 33 (16.3%) 91 (44.9%) GV n 5 93 6 (6.5%)* 3 (3.2%)* 8 (8.6%)† 4 (4.3%)* 18 (19.3%)* *P ,0.05 compared to MII oocytes. †P 50.06 compared to MII oocytes. The data shows that there was a significant difference (P,0.05, Chi Square Test) between the frequency of aneuploidy in MII and GV oocytes for chromosomes 11, 17 and 22 and was bordering on significance for chromosome 16. There was a significant difference (P,0.05, Chi Square Test) in the number of GV oocytes and MII oocytes that were aneuploid for at least one of the four chromosomes. Conclusions: We have shown that aneuploidy occurs in GV oocytes at a frequency of approximately 6% for each of the chromosomes tested, and that almost 20% of GV oocytes have an aneuploidy. The frequency of aneuploidy was significantly greater in MII oocytes confirming that many aneuploidies also occur during the first meiotic division. Importantly, it has also shown that a significant number of oocytes are aneuploid even prior to metaphase I.