Robert Kuo-Kuang Lee

Poor Response of Ovaries with Endometrioma Previously Treated with Cystectomy to Controlled Ovarian Hyperstimulation

AbstractPurpose: To compare ovarian response to controlled ovarian hyperstimulation (COH) between normal ovaries and ovaries previously treated surgically for unilateral ovarian endometrioma. Methods: From January 1996 to December 2001, 32 patients with unilateral ovarian endometrioma previously treated surgically underwent 38 cycles of COH. Their records were reviewed retrospectively. The number of dominant follicles observed on the day of hCG injection and the number of eggs retrieved from the diseased and the normal ovaries in each patient were compared. Results: The numbers of dominant follicles from diseased and normal ovaries were 1.9 ±1.5 and 3.3 ± 2.1, respectively (P < 0.001). During ovum pick up, the numbers of eggs retrieved from diseased and normal ovaries were 2.9 ± 2.6 and 6.1 ± 4.1, respectively (P < 0.0001). For diseased ovaries, 21.1% (8/38) had no dominant follicles, while only 7.9% (3/38) of normal ovaries lacked dominant follicles. The clinical pregnancy rate and the implantation rate per embryo transfer were 33.3 and 17.6%. Conclusions: Surgery for ovarian endometrioma may damage ovarian reserve. It potentially results in poor ovarian response to COH, compared to the response of the contralateral normal ovary in the same individual.

The impact of endometrioma and laparoscopic cystectomy on serum anti-Müllerian hormone levels

BackgroundSerum anti-Müllerian hormone (AMH) had been proposed as a marker of ovarian reserve. The aim of this study was to evaluate the impact of endometrioma and laparoscopic cystectomy on ovarian reserve as measured by serum AMH levels.MethodsA total of 1,642 patients were recruited in this retrospective analysis. Control group (group 1) included 1,323 infertility patients without endometrioma. Endometrioma group (group 2) included 141 patients with ovarian endometrioma. Previous cystectomy group (group 3) included 147 patients who underwent unilateral or bilateral laparoscopic cystectomy due to ovarian endometrioma more than 6 months before enrollment. Current cystectomy group (group 4) included 31 patients who underwent cystectomy during study period. Serum anti-müllerian hormone (AMH) levels were measured upon enrollment with all patients. For patients in group 4, AMH levels were measured before and 3 months after cystectomy.ResultsMean AMH level of patients in control group was significantly higher than that of endometrioma group or previous cystectomy group in each age subgroup, while the mean serum AMH level of the endometrioma group was also significantly higher than that of the previous cystectomy group in each age subgroup. The mean AMH level was significantly lower in patients with previous bilateral cystectomy compared to that of patients with unilateral cystectomy. The mean serum AMH level was also significantly lower in patients with bilateral endometrioma compared to that of patients with unilateral endometrioma. In group 4, mean AMH level significantly decreased from 3.95 +/- 0.42 preoperation to 2.01 +/- 0.21 ng/ml at 3-month postoperation.ConclusionsBoth ovarian endometrioma and cystectomy are associated with a significant reduction on ovarian reserve. Bilateral endometrioma exerts a more profound negative impact on ovarian reserve than unilateral endometrioma, regardless of either conservative or surgical intervention.

Identification of a novel platelet-derived growth factor-like gene, fallotein, in the human reproductive tract.

We isolated the cDNA of a novel platelet-derived growth factor-like gene from human endometrium. The gene was named fallotein; it was 3007 bases in length, and encoded a protein of 345 amino acids. Antiserum against the fallotein protein can recognize a specific protein in the fallopian tube, with a molecular size in accordance with the anticipated size of fallotein. Fallotein mRNA is expressed in two molecular sizes, 3.8 and 2.9 kb, with the former being more abundant. High expression of the gene was found in the prostate, testis, and uterus. A weaker expression signal was found in the spleen, thymus, and small intestine, but expression of fallotein in the colon and peripheral blood leukocytes was negligible.

Ultra-short metformin pretreatment for clomiphene citrate-resistant polycystic ovary syndrome

Objective: To evaluate the effect of ultra‐short (12 days) metformin pretreatment in clomiphene‐citrate (CC) resistant polycystic ovary syndrome (PCOS). Method: Eighty women with CC‐resistant PCOS were randomly allocated to metformin pretreatment or usual treatment. Forty women received 1500 mg metformin daily for 12 days, followed by clomiphene 150 mg daily for 5 days along with metformin. Forty women (control group) received the same dose of clomiphene but no metformin pretreatment. Results: In the metformin group, 17 (42.5%) women ovulated, and 6 (15%) conceived. In the control group, 5 (12.5%) women ovulated but none conceived. Compared with the control group, the metformin group had significantly higher ovulation (P = 0.03) and pregnancy rates (P = 0.026). Conclusion: Twelve days of metformin pretreatment improves ovulation and pregnancy rates in women with CC‐resistant PCOS.

Cessation of Low-Dose Gonadotropin Releasing Hormone Agonist Therapy Followed by High-Dose Gonadotropin Stimulation Yields a Favorable Ovarian Response in Poor Responders

AbstractPurpose: This study is a prospective nonrandomized study to determine the effect of a new protocol of controlled ovarian hyperstimulation (COH) using low doses and a half-period of gonadotropin releasing hormone agonist (GnRHa) followed by high doses of gonadotropin in patients who were supposed to be poor responders to standard long protocols of GnRHa administration. Methods: From Dec 1996 to Nov 1998, 50 patients who were classified as “poor responders” were scheduled for 52 cycles of a modified controlled ovarian hyperstimulation protocol. They were categorized into 3 groups: a group of poor responders to COH in the previous IVF or IUI cycles, a group with elevated Day 3 FSH levels, and a group over the age of 40 years. All patients received GnRH agonist from the midluteal phase of the previous cycle to the onset of menstruation in the next cycle. Then high doses of gonadotropins (HMG/FSH) were given. The patients then had standard courses of in vitro fertilization and embryo transfer (IVF-ET) or transfallopian embryo transfer (TET). Results: Six of the 52 cycles of the modified protocols were cancelled because of poor ovarian response. One premature ovulation was noted before ovum retrieval was performed. In the other 45 cycles, an average of 6.3 mature oocytes were retrieved. The total pregnancy rate and implantation rate were 20.5 and 11.5%, respectively. Conclusions: The low dose and half duration of GnRHa therapy lessened the suppression of the response of the ovaries to COH compared with the regular long protocol of GnRHa down regulation therapy. This resulted in a low cancellation rate (11.8%), a favorable embryo implantation rate (11.5%), and an acceptable clinical pregnancy rate (20.5%).

Paracrine factors from human placental multipotent mesenchymal stromal cells protect endothelium from oxidative injury via STAT3 and manganese superoxide dismutase activation.

Reactive oxygen species may cause oxidative damage in the placenta, yet some mechanisms must exist to reduce or prevent such damage. We investigated whether oxidative injury to placental endothelial cells is inhibited by activation of antioxidant enzymes by paracrine factors secreted by human placental multipotent mesenchymal stromal cells (hPMSC). hPMSC-conditioned medium and umbilical endothelial cells were assayed for cytokines and cytokine receptor expression by immunoassay and real-time PCR. Endothelial cell survival was evaluated by MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt] assay and caspase 3 activity assay. tert-Butyl hydroperoxide was used to induce oxidative injury in endothelial cells, with fluorescent microscopy and flow cytometry used to detect intracellular peroxides and cell apoptosis. Western blot, real-time PCR, STAT3 DNA-binding activity assay, and STAT3 siRNA were used to assess endothelial cell antioxidant enzymes. hPMSC-conditioned medium supported endothelial cell survival and reduced endothelial cell intracellular peroxides and apoptosis. hPMSCs expressed the transcripts of the interleukin (IL) 6 cytokine family, including IL6 and leukemia-inhibitory factor. hPMSC-conditioned medium activated STAT3 expression in endothelial cells, which was inhibited by neutralizing antibody to interleukin 6 signal transducer (IL6ST) but not to IL6 or leukemia-inhibitory factor. STAT3 siRNA or manganese superoxide dismutase (SOD2) siRNA transfected into endothelial cells inhibited the antiapoptotic effect of conditioned medium. SOD2 was significantly upregulated in endothelial cells by conditioned medium via STAT3 activation that, in turn, was inhibited by IL6ST-neutralizing antibody or STAT3 siRNA. Paracrine factors secreted by hPMSCs support endothelial cell survival. STAT3 activation and SOD2 production protect against oxidative stress-induced endothelial cell damage.

Demonstration of a Glycoprotein Derived From the Ceacam10 Gene in Mouse Seminal Vesicle Secretions

Abstract CEACAM10 was purified from mouse seminal vesicle secretions by a series of purification steps that included ion exchange chromatography on a DEAE-Sephacel column and ion exchange high-performance liquid chromatography on a sulfopropyl column. It was shown to be a 36-kDa glycoprotein with an N-linked carbohydrate moiety. The circular dichromoism spectrum of CEACAM10 in 50 mM phosphate buffer at pH 7.4 appeared as one negative band arising from the β form at 217 nm. CEACAM10 was expressed predominantly in seminal vesicles of adult mice. Both CEACAM10 and its mRNA were demonstrated on the luminal epithelium of the mucosal folds in the seminal vesicle. The amount of Ceacam10 mRNA in the seminal vesicle was correlated with the stage of animal maturation. Castration of adult mice resulted in cessation of Ceacam10 expression, while treatment of castrated mice with testosterone propionate in corn oil restored Ceacam10 expression in the seminal vesicle. During the entire course of pregnancy, Ceacam10 might be silent in the embryo. A cytochemical study illustrated the presence of the CEACAM10 binding region on the entire surface of mouse sperm. CEACAM10-sperm binding greatly enhanced sperm motility in vitro.

The Effects of Brief Gamete Co-incubation in Human In Vitro Fertilization

AbstractPurpose: To investigate whether very short exposure ofmature oocytes to sperm in vitro may affect the fertilizationrates, embryo cleavage rates, and embryo quality betweensibling oocytes in the same patient. Methods: Sibling oocytes of the same patient from 23 oocytecollection cycles were randomly allocated to the study group,with a 1-hr or 3-hr sperm—oocyte incubation, or the controlgroup with the standard overnight gamete co-incubation.The fertilization rates, cleavage rates, and subsequentembryo quality were evaluated. Results: Our results showed no statistically significant differencesin fertilization rates, embryo cleavage rates, andquality of the embryos between the study group and thecontrol group. Conclusions: Since the present study showed that long exposureof the oocyte to sperm has no advantage over shortexposure, we prefer shortening the oocyte—sperm incubationperiod for reducing the negative effect induced bynonphysiologically high concentrations of spermatozoa.

In vivo hatching phenomenon of mouse blastocysts during implantation.

Purpose: To determine whether the blastocyst zona shedding process within the murine uterine cornus in vivo is due to a global lytic process caused by uterine proteolytic enzyme, or is triggered by the blastocyst hatching process as observed in vitro.Methods: Fifty-one female ICR mice aged 5–8 weeks were used for this study. From 8:00 p.m. of the 4th day postcoitus to 7:00 p.m. of the 5th day postcoitus, the uterine cornua of 51 mice were isolated at 30-min intervals. Blastocysts within the uterine cornua were flushed out with a balanced solution under the dissecting microscope. The stages of blastocyst development and the proportion of hatching or hatched blastocysts and the discarded zona pellucida (ZP) were inspected and counted.Results: A total of 672 blastocysts were recovered from the uterine horns of the 51 mice. They were divided into six groups according to the blastocyst developmental stages (before or after ZP escape; before or after the initiation of implantation). Group I represents the earliest embryonic stage and Group VI represents the most advanced blastocyst developmental stage during the peri-implantation period. The empty ZP recovery rates (number of discarded ZP/all hatched blastocysts) were 52.3%, 21.5%, 17.2%, 6.6%, 1.6%, and 0% in Groups I–VI, respectively. Five hatching blastocysts out of 199 embryos in Group I were found and a 100% of ZP recovery rate was obtained from 6 of 19 mice in Groups I and II.Conclusions: The present study shows that active blastocyst hatching occurs in vivo because both hatching blastocysts and empty ZP can be found within the uterine cornua of ICR mice before implantation. The empty ZP recovery rate declined significantly, along with a progression of embryo development and implantation, implying that intrauterine zona lytic activity occurs during the peri-implantation stage.

A successful pregnancy with in vitro fertilization and embryo transfer in an infertile woman with Kartagener's syndrome : A case report

Kartageners syndrome (KS), a subgroup of the immotile-dyskinetic cilia syndrome, is a rare congenital disorder in the axoneme of the cilia characterized by the classic triad of recurrent rhinosinusitis, bronchiectasis, and situs inversus (1). The prevalence of this syndrome has been estimated at 1 in 40,000 (2). Up to the present time, it is generally considered that males with KS are almost all infertile (3,4), but the situation in female patients is not so clear. Some women with this syndrome are infertile (5-7), whereas some have successfully conceived (8-10). Although pregnancy is not impossible in women with KS, they are at high risk for sterility. Afzelius et al. reported only three successful pregnancies in 12 women with KS who tried to conceive (11). Recently, Halber and co-workers reported initial work with in vitro fertilization (IVF) and embryo transfer (ET) for a woman with infertility due to dyskinetic oviductal cilia caused by KS (7). Unfortunately, their patient did not conceive from that single IVF-ET attempt. Our study provides the first report of a successful pregnancy with IVF-ET in an infertile woman with KS. In addition, we are also the first to report an ectopic pregnancy in this syndrome.