Ming-Huei Lin

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.

Plasma membrane integrity of cryopreserved human sperm: an investigation of the results of the hypoosmotic swelling test, the water test, and eosin-y staining

OBJECTIVE [1] To examine the relationship between sperm membrane integrity and motion parameters before and after cryopreservation; [2] to determine the capacity of the membrane integrity tests to predict the outcome of cryopreservation in fertile and infertile men; and [3] to examine the degree of agreement between tail and head membrane integrity of testicular and ejaculated immotile sperm cryopreserved for intracytoplasmic sperm injection. DESIGN Prospective study. SETTING Academic tertiary care institution. PATIENT(S) Fertile donors and normozoospermic oligozoospermic, and asthenozoospermic subfertile men. INTERVENTION(S) Semen samples were cryopreserved and thawed for analysis. MAIN OUTCOME MEASURE(S) Sperm membrane integrity and computer-assisted motion parameters. RESULT(S) The hypoosmotic swelling test and water test had a significant and positive correlation in the fresh and cryopreserved ejaculates of all groups. The results of the hypoosmotic swelling test correlated positively with the percent motility in the fresh ejaculates of fertile and subfertile men. None of the membrane integrity tests correlated with the cryosurvival rate in any group. In the ejaculated and testicular samples with no postcryopreservation motility, the simultaneous assessment of hypoosmotic swelling test and eosin showed that of 33% sperm exhibiting coiling with the hypoosmotic swelling test, only 9% were eosin negative, whereas 24% were eosin positive. CONCLUSION(S) [1] The water test may be a simpler replacement for the hypoosmotic swelling test; [2] none of the membrane integrity tests predicted sperm motility after cryopreservation; and [3] there was a high degree of disagreement between the hypoosmotic swelling test and eosin in the samples with no postcryopreservation motility.

Dual trigger with combination of gonadotropin-releasing hormone agonist and human chorionic gonadotropin significantly improves the live-birth rate for normal responders in GnRH-antagonist cycles

OBJECTIVE To investigate whether dual triggering of final oocyte maturation with a combination of gonadotropin-releasing hormone (GnRH) agonist and human chorionic gonadotropin (hCG) can improve the live-birth rate for normal responders in GnRH-antagonist in vitro fertilization/intracytoplasmic sperm injection (IVF-ICSI) cycles. DESIGN Retrospective cohort study. SETTING Infertility unit of a university-affiliated medical center. PATIENT(S) Normal responders to controlled ovarian hyperstimulation who were undergoing IVF-ICSI with a GnRH antagonist protocol. INTERVENTION(S) Standard dosage of hCG trigger (6,500 IU of recombinant hCG) versus dual trigger (0.2 mg of triptorelin and 6,500 IU of recombinant hCG). MAIN OUTCOME MEASURE(S) Live-birth, clinical pregnancy, and implantation rates per cycle. RESULT(S) A total of 376 patients with 378 completed cycles with embryo transfer were enrolled (hCG trigger/control group: n = 187; dual trigger/study group: n = 191). The dual trigger group demonstrated statistically significantly higher implantation (29.6% vs. 18.4%), clinical pregnancy (50.7% vs. 40.1%), and live-birth (41.3% vs. 30.4%) rates as compared with the hCG trigger group. There was no statistically significant difference in terms of patient demographics, cycle parameters, or embryo quality. CONCLUSION(S) Dual trigger of final oocyte maturation with a GnRH-agonist and a standard dosage of hCG in normal responders statistically significantly improves implantation, clinical pregnancy, and live-birth rates in GnRH-antagonist IVF cycles.

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%).

The predictability of serum anti-Müllerian level in IVF/ICSI outcomes for patients of advanced reproductive age

BackgroundThe role of serum anti-Müllerian hormone (AMH) as predictor of in-vitro fertilization outcomes has been much debated. The aim of the present study is to investigate the practicability of combining serum AMH level with biological age as a simple screening method for counseling IVF candidates of advanced reproductive age with potential poor outcomes prior to treatment initiation.MethodsA total of 1,538 reference patients and 116 infertile patients aged greater than or equal to 40 years enrolled in IVF/ICSI cycles were recruited in this retrospective analysis. A reference chart of the age-related distribution of serum AMH level for Asian population was first created. IVF/ICSI patients aged greater than or equal to 40 years were then divided into three groups according to the low, middle and high tertiles the serum AMH tertiles derived from the reference population of matching age. The cycle outcomes were analyzed and compared among each individual group.ResultsFor reference subjects aged greater than or equal to 40 years, the serum AMH of the low, middle and high tertiles were equal or lesser than 0.48, 0.49-1.22 and equal or greater than 1.23 ng/mL respectively. IVF/ICSI patients aged greater than or equal to 40 years with AMH levels in the low tertile had the highest cycle cancellation rate (47.6%) with zero clinical pregnancy. The nadir AMH level that has achieved live birth was 0.56 ng/mL, which was equivalent to the 36.4th percentile of AMH level from the age-matched reference group. The optimum cut-off levels of AMH for the prediction of nonpregnancy and cycle cancellation were 1.05 and 0.68 ng/mL, respectively.ConclusionsTwo criteria: (1) age greater than or equal to 40 years and (2) serum AMH level in the lowest tertile (equal or lesser than 33.3rd percentile) of the matching age group, may be used as markers of futility for counseling IVF/ICSI candidates.

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.

Involvement of the Serine Protease Inhibitor, SERPINE2, and the Urokinase Plasminogen Activator in Cumulus Expansion and Oocyte Maturation

The serpin peptidase inhibitor, clade E, member 2 (SERPINE2) inhibits urokinase-type plasminogen activator (PLAU) and tissue-type plasminogen activator. Higher SERPINE2 expression levels were detected in cumulus cells of human immature oocytes than in those of mature oocytes. The objective of this study was to evaluate whether high SERPINE2 levels in cumulus cells are associated with oocyte immaturity. Using the mouse cumulus–oocyte complex as an experimental model, the effects of elimination and overexpression of SERPINE2 in cumulus cells on cumulus expansion and oocyte maturation were assayed by in vitro maturation. Serpine2 and PLAU transcripts were the most highly expressed serpins and plasminogen activators, respectively. Their expression was coordinately regulated in cumulus cells during gonadotropin-induced oocyte maturation. Silencing of Serpine2 expression using small interfering RNAs or blockage of SERPINE2 protein using a specific antibody had no effect on oocyte maturation. However, overexpression of Serpine2 or exogenous supplementation with high levels of SERPINE2 impaired cumulus expansion and oocyte maturation, probably by decreasing hyaluronan synthase 2 (Has2) and versican (Vcan) mRNA expression. Amiloride, a specific PLAU inhibitor, also suppressed these processes. PLAU supplementation of the oocyte in vitro maturation medium caused earlier and more extensive expansion of cumulus cells and oocyte maturation that may be mediated by increased Has2 mRNA expression. However, these effects were neutralized by coincubation with SERPINE2 or amiloride and PLAU. In conclusion, SERPINE2 and PLAU are involved in cumulus expansion and oocyte maturation. High SERPINE2 levels impair these processes, probably by decreasing cumulus matrix gene expression as well as reducing cumulus hyaluronan contents and inhibiting PLAU activity. These findings may explain why cumulus cells surrounding immature human oocytes express high SERPINE2 levels.

Mechanisms underlying the inhibition of murine sperm capacitation by the seminal protein, SPINKL.

SPINKL, a serine protease inhibitor kazal‐type‐like protein initially found in mouse seminal vesicle secretions, possesses structurally conserved six‐cysteine residues of the kazal‐type serine protease inhibitor family. However, it has no inhibitory activity against serine proteases. Previously, it was found to have the ability to suppress murine sperm capacitation in vitro. Herein, we investigated the mechanisms underlying the suppressive effect of SPINKL on sperm capacitation. Three in vitro capacitation‐enhancing agents, including bovine serum albumin (BSA), methyl‐beta‐cyclodextrin (MBCD), and dibutyryl cyclic AMP (dbcAMP), coupled with 3‐isobutyl‐1‐methylxanthine (IBMX), were used to evaluate the influence of SPINKL on capacitation signaling. Preincubation of sperm with SPINKL suppressed BSA‐ and MBCD‐induced sperm capacitation by blocking three upstream signals of capacitation that is the cholesterol efflux from sperm plasma membranes, extracellular calcium ion influx into sperm, and increases in intracellular cAMP. Moreover, SPINKL also inhibited downstream signal transduction of capacitation since it suppressed dbcAMP/IBMX and N6‐phenyl cAMP (6‐Phe‐cAMP)‐activated cAMP‐dependent protein kinase‐associated protein tyrosine phosphorylation. Such inhibition is probably mediated by attenuation of SRC tyrosine kinase activity. Furthermore, SPINKL could not reverse capacitation once sperm had been capacitated by capacitation‐enhancing agents or capacitated in vivo in the oviduct. SPINKL bound to sperm existed in the uterus but had disappeared from sperm in the oviduct during the sperms transit through the female reproductive tract. Therefore, SPINKL may serve as an uncapacitation factor in the uterus to prevent sperm from precocious capacitation and the subsequent acrosome reaction and thus preserve the fertilization ability of sperm. J. Cell. Biochem. 114: 888–898, 2013.