Making Education Easy
Issue 6 - 2014
Welcome to the 6th issue of Fertility Research Review
In this issue we review several studies investigating sperm quality. Many men are unaware that the use of finasteride, a common treatment for baldness, reduces sperm counts. Fortunately for couples desiring fertility, sperm counts were shown to increase on cessation of finasteride treatment. Couples may also need to reconsider use of lubricants as some are shown to have detrimental effects on sperm motility in an in vitro study. Using IMSI for sperm selection increased pregnancy rates in older women in a prospective randomised study. Other studies reviewed this issue show increased pregnancy rates with ICSI preceded by endometrial injury and in egg donor recipients with replete vitamin D levels. The mechanisms for these influential factors are not yet understood.
We hope you enjoy our selection for this edition and your comments and feedback are welcome.
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Dr Mary Birdsall
Fertility treatments and multiple births in the United States
Authors: Kulkarni AD, et al.
Summary: The increased use of fertility treatments in the United States has been associated with a
substantial rise in the rate of multiple births. The proportion of multiple births that were attributable to
IVF and non-IVF fertility treatments from 1997 through 2011 was estimated and compared with rates of multiple births after natural conception. A total of 36% of twin births and 77% of triplet and higher-order births resulted from conception assisted by fertility treatments. The observed incidence of twin births increased by a factor of 1.9 from 1971 to 2009. The incidence of triplet and higher-order births increased by a factor of 6.7 from 1971 to 1998, but decreased by 29% from 1998 to 2011 when clinical practice guidelines for IVF had been developed. During this time there was a 70% reduction in the transfer of three or more embryos for IVF (p<0.001).
Comment: Multiple pregnancies have been the dirge of the fertility world. This report estimates that
more than a third of all twins occur as a result of fertility treatments and more than three quarters of
all triplets. These multiple pregnancies are almost all avoidable with the adoption of a single embryo
Abbreviations used in this issue
transfer policy. Freezing technology has improved so that frozen embryos almost always survive FSH = follicle-stimulating hormone
thawing and implantation rates are the same as fresh implantation rates. I would hope that the US hCG = human chorionic gonadotropin
continues to see a decline in multiple births as a result of fertility treatments.
ICS = intracytoplasmic sperm injection
IMSI = intracytoplasmic morphologically selected
sperm injection Reference: N Engl J Med. 2013;369:2218-2225
IUI = intra-uterine insemination
IVF = in vitro fertilisation
NS = not significant
OR = odds ratio
Fertility Research Review
Independent commentary by Dr Mary Birdsall,
BHB MB ChB Auckland; FRANZCOG MSc (Oxon)
Mary is the Medical Director of Fertility Associates' Auckland clinic and combines this with a
private gynaecology practice. She has a special interest in fertility preservation and the lifestyle
influences on fertility. Mary is the New Zealand representative to the Fertility Society of Australia's
IVF Directors Group executive and the editor of the book ‘Making Babies'.
a RESEARCH REVIEW publication
Fertility Research Review
Finasteride use in the male infertility population: effects on
In vitro effects of coital
semen and hormone parameters
lubricants and synthetic and
Authors: Samplaski MK, et al.
natural oils on sperm motility
Summary: Finasteride, even at low doses, may cause reduced sperm counts in some men. This prospective
Authors: Sandhu RS, et al.
study compared semen and hormone parameters before and after discontinuation of finasteride in 27 men Summary: The effects of coital lubricants and oils
presenting for fertility evaluation. The mean dose of finasteride was 1.04 mg/day and the mean duration of on sperm motility were evaluated in this in vitro treatment was 57.4 months. Sperm counts increased dramatically for the majority of men after finasteride study. Semen samples from 22 normozoospermic discontinuation. There was an average 11.6-fold increase in sperm counts; no man had a decrease in donors were incubated in modified human tubal sperm count. Of the men with severe oligospermia (<5 M/mL), 57% had counts increase to >15 M/mL after fluid control and in 10% Pre-Seed, Astroglide, and finasteride cessation. Hormone parameters, sperm motility, and sperm morphology were unchanged after KY products (Sensitive, Warming, and Tingling) and cessation. The authors concluded that ‘finasteride should be discontinued in subfertile men with oligospermia, baby, canola, sesame, and mustard oils. Total and and used with caution in men who desire fertility'.
progressive sperm motility was evaluated before and at 5, 30, and 60 minutes of incubation. There Comment: Finasteride is a commonly used medication for the treatment of male baldness and is often
was no significant decrease in sperm motility in obtained from internet pharmacies. Most men are unaware that the use of finasteride may be associated control samples. Astroglide, KY products (Sensitive, with a reduction in sperm quality. This is a very useful study and suggests that men who are attempting to Warming, and Tingling) and sesame oil incubation conceive should stop finasteride. Cessation of the drug may cause an improvement in semen parameters significantly decreased total and progressive sperm particularly in men with a suboptimal semen analysis.
motility. Pre-Seed, canola oil and baby oil initially decreased sperm motility, but total and progressive sperm motility remained high. Mustard oil caused persistent hyperactivation of sperm with no decrease in motility and needs to be studied further. The authors concluded that ‘Pre-Seed and canola, mustard, and baby oils showed no deleterious effect and may be Guiding your patient considered sperm-friendly coital lubricants'.
every step of the way
Comment: Many couples are unaware that the
use of some lubricants may be associated with
a detrimental effect on sperm and hence reduce
the chances of conception. This study shows that
Pre-Seed has the least impact on in vitro sperm
motility. The best advice for couples who are
attempting to conceive, is to use no lubricant or if
necessary Pre-Seed, baby oil or canola oil appear
to be the lubricants of choice.
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Fertility Research Review
Increasing the probability of selecting
Subcutaneous progesterone versus vaginal
chromosomally normal embryos by
progesterone gel for luteal phase support in in vitro
time-lapse morphokinetics analysis
fertilization: a noninferiority randomized controlled
Authors: Basile N, et al.
Summary: The differences in cleavage time between Authors: Lockwood G, et al.
chromosomally normal and abnormal embryos were Summary: The safety, efficacy and tolerability of subcutaneous progesterone (Prolutex)
retrospectively analysed using a time-lapse system. A total of were compared with vaginal progesterone gel (Crinone) for luteal phase support in 504 embryos undergoing preimplantation genetic screening 683 patients undergoing IVF. Patients were randomised to receive Prolutex 25 mg (n=339) were analysed from 125 patients, including those with repeated and Crinone 90 mg 8% gel (n=344) on the day of oocyte retrieval and daily for up to implantation failure or recurrent miscarriage. Logistic regression 10 weeks. Prolutex was found noninferior to Crinone based on the ongoing pregnancy analysis identified the interval between the time to 5 cells and rate at 10 weeks of treatment (27.4% vs 30.5%; NS). Delivery and live birth rates were time to 2 cells (OR 2.853; 95% CI 1.763–4.616), followed by the equivalent between the two treatments (26.8% vs 29.9%). Implantation rate, pregnancy length of the third cell cycle (OR 2.095; 95% CI 1.356–3.238) rate, and early miscarriage rate for Prolutex were also similar to those for Crinone. There as the most relevant variables related to normal chromosomal were no differences reported for comfort of usage and overall satisfaction. Adverse event content. These results were used to develop an algorithm to profiles were similar and Prolutex was safe and well tolerated. classify embryos from A to D and increase the probability for noninvasive selection of normal embryos. Each category exhibited Comment: Luteal phase support with progesterone is necessary following the use of
significant differences in the percentage of normal embryos: A, IVF drugs. Most clinics use vaginal progesterone which is sometimes continued into 35.9%; B, 26.4%; C, 12.1%; D, 9.8%.
the first trimester of pregnancy. Vaginal progesterone is associated with an unpleasant vaginal discharge which most women tolerate but would prefer an alternate option. Comment: The latest tool in the IVF lab is time-lapse
This is a study looking at a daily subcutaneous injection of progesterone and appears microscopy. This is where embryos being cultured in incubators to show similar efficacy to vaginal progesterone. There was no difference in satisfaction are photographed every 15 minutes. This information is then scores suggesting that a better tolerated progesterone is still needed.
analysed to help improve embryo selection. This study shows that time-lapse microscopy may assist embryologists to choose chromosomally normal embryos. The disappointing feature however is that still only 36% of embryos in the most favourable group were normal.
A randomised controlled trial of intra-uterine
insemination versus in vitro fertilisation in patients
with idiopathic or mild male infertility
Authors: Elzeiny H, et al.
Influence of vitamin D levels on
Summary: IVF was found to be more successful and cost-effective than IUI using the
in vitro fertilization outcomes in
same doses of FSH in this randomised controlled study in couples with idiopathic or mild male infertility for ≥1 year. All women (n=102) received the same dose FSH stimulation Authors: Rudick BJ, et al.
protocol and those who developed two or three preovulatory follicles were randomised 3:1 to IUI (n=33) or IVF (n=10). IUI or IVF was performed 36 hours after hCG administration Summary: The relationship between recipient vitamin D levels and
with single or double embryo transfer on day 2. The IVF group had a higher clinical pregnancy rates in donor-recipient IVF cycles was retrospectively pregnancy rate (40% vs 12%; p=0.04) and live birth rate (40% vs 6%; p=0.01) than IUI. examined to elucidate the role of vitamin D in reproduction. The cost per live birth was AU$8735 for IVF compared with $42,487 for IUI.
Vitamin D [25(OH)D] levels were measured in serum collected from 99 egg donor recipients before embryo transfer. Adjusted Comment: This Melbourne-based study shows that IVF has a higher pregnancy rate
clinical pregnancy rates (defined by sonographic presence and costs less per baby when compared with IUI in couples with unexplained or mild of a heartbeat at 7-8 weeks of gestation) were lower among male factor infertility. It also demonstrates one of the failings of IUI which is the high rate vitamin D-deficient recipients compared with vitamin D-replete of multiple pregnancies, with half of the pregnancies in the IUI group being multiples. recipients (37% vs 78%). Live birth rates were also lower among This is no longer seen in IVF programmes with the advent of single embryo transfers. vitamin D-deficient recipients (31% vs 59%). There were no The ovarian stimulation regimen in this study was exactly the same for both IUI and IVF differences in adjusted clinical pregnancy and live-birth rates and also demonstrated excellent pregnancy rates on minimal stimulation IVF.
among recipients with vitamin D levels <20 ng/mL (deficient) and those with vitamin D levels 20-29 ng/mL (insufficient). The Reference: Aust N Z J Obstet Gynaecol. 2014;54(2):156-61
authors commented that ‘these data suggest that the effects of vitamin D may be mediated through the endometrium'.
Comment: Replete vitamin D levels are associated with a
ideal way of exploring whether vitamin D is important for the to anyone without your prior approval. Research Review and you have the right to inspect, update or delete your details at any time.
endometrium or the egg.
Disclaimer: This publication is not intended as a replacement for regular medical education but to assist in
the process. The reviews are a summarised interpretation of the published study and reflect the opinion of the writer rather than those of the research group or scientific journal. It is suggested readers review the full trial data before forming a final conclusion on its merits. Research Review publications are intended for New Zealand Medical Professionals
a RESEARCH REVIEW publication
Fertility Research Review
Endometrial injury may increase the clinical pregnancy rate in
normoresponders undergoing long agonist protocol ICSI cycles
sperm injection is beneficial with single embryo transfer
in cases of advanced
Authors: Guven S, et al.
maternal age: a prospective
Summary: The effect of endometrial injury on the clinical pregnancy rate in normoresponders undergoing
long agonist protocol ICSI cycles with single embryo transfer was investigated in this prospective case-control study in 118 women aged <35 years. All women had grade I or II embryos for transfer. Women Authors: Setti AS, et al.
in the intervention group (n=56) underwent endometrial biopsy on day 3 of the menstrual cycle following Summary: IMSI increased the implantation
downregulation; women in the control group (n=62) did not undergo endometrial biopsy. Clinical and rate and odds of pregnancy in this prospective embryological characteristics were comparable and fertilisation rates were not significantly different randomised study of 66 couples undergoing between the intervention and control groups (66.32% vs 70.23%). The clinical pregnancy rate was ICSI as a result of advanced maternal age significantly higher in the intervention group (48.2% vs 29.0%; p=0.025) as was the take-home baby rate (≥37 years). Sperm selection in the ICSI group (33.9% vs 17.7%; p=0.035). Endometrial injury may increase the clinical pregnancy rate (OR 2.27).
(n=33) was analysed under a magnification of 400x and sperm selection in the IMSI group Comment: Endometrial injury in the menstrual cycle prior to embryo implantation may increase
(n=33) was analysed under high magnification the chances of a successful pregnancy. This observation is nothing new as an increased chance of 6600x. Implantation rates (38.3% vs 12.1%; of conceiving is seen following an evacuation for a miscarriage, after a D and C and following a p=0.026) and pregnancy rates (60.0% vs hysterosalpingogram. The mechanism by which endometrial injury improves implantation is unknown. 13.8%; p<0.001) were higher in the IMSI This was a well-designed study in which the endometrial biopsy was performed 3 days after down group than ICSI group. The IMSI procedure regulation was confirmed. Endometrial biopsy in the same cycle as implantation occurs has been positively influenced the blastocyst formation shown to be detrimental and biopsies in the luteal phase of the preceding month can be complicated by rate (p=0.001) and implantation rate (p=0.027) and increased the odds of pregnancy (OR 9.0; 95% CI 2.17–37.38; p=0.001). The Reference: Eur J Obstet Gynecol Reprod Biol. 2014;173:58-62
authors suggested that ‘the injection of a morphologically normal spermatozoon overcomes the low oocyte quality in older women' and the resulting improved embryo Influenza and congenital anomalies:
quality translates to a 9-fold increase in a systematic review and meta-analysis
the clinical pregnancy rate in couples with Authors: Luteijn JM, et al.
advanced maternal age. Summary: First trimester maternal influenza exposure was associated with an increased risk of non-
Comment: IMSI is a new IVF technology
chromosomal congenital anomalies in this meta-analysis of 22 studies published up to July 2013. The meta- for sperm selection. The theory is that analysis included 29,542 babies with congenital anomaly (1112 exposed) from case-control studies and by magnifying sperm up to 6600x then 1608 exposed pregnancies resulting in 56 babies with congenital anomaly from cohort studies. An adjusted a better selection is possible for sperm OR of 2.00 (95% CI 1.62–2.48) was found for risk of any congenital anomaly for first trimester maternal injection. There have been a number of influenza exposure. ORs for specific anomalies included 3.33 for neural tube defects (95% CI 2.05–5.40), studies reported with conflicting results as 5.74 for hydrocephaly (95% CI 1.10–30.00), 1.56 for congenital heart defects (95% CI 1.13–2.14), 3.12 to who will most benefit from IMSI. There is for cleft lip (95% CI 2.20–4.42), 1.72 for digestive system defects (95% CI 1.09–2.68) and 2.03 for limb no evidence that IMSI improves take-home reduction defects (95% CI 1.27–3.27). Adjusted ORs were 2.59 for aortic valve atresia/stenosis (95% baby rates in a general ICSI population CI 1.21–5.54) and 1.59 for ventricular septal defect (95% CI 1.24–2.14). The authors concluded that (in ICSI sperm are selected at 400x ‘prevention of influenza in pregnant women may reduce congenital anomaly risk and would be relevant to magnification). This study suggests that more than just neural tube defects'.
for older women (≥37 years) with a higher number of chromosomally abnormal eggs, Comment: As we approach influenza season, this review is a timely reminder that influenza can result in
selecting a normal sperm may improve a number of negative outcomes, including an increase in foetal abnormalities. We should be encouraging take-home baby rates.
women who are trying for a pregnancy to have their flu shots and to avoid sick people, particularly in early pregnancy.
Reference: Eur J Obstet Gynecol Reprod
Reference: Hum Reprod. 2014;29(4):809-23
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2014 RESEARCH REVIEW
Age and Ageing 2015; 44: 213–218 © The Author 2014. Published by Oxford University Press on behalf of the British Geriatrics Society. This is an Open Access article distributed under the terms of the Creative Commons Attribution Published electronically 16 October 2014 Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is
Bulletin of Pharmaceutical Research 2012;1(S):41 An Official Publication of Association of Pharmacy Professionals ISSN: 2249-6041 (Print); ISSN: 2249-9245 (Online) GASTRORETENTIVE TARGETING TECHNOLOGY FOR ERADICATION OF HELICOBACTER PYLORI INFECTION Rakesh Pahwa*, Lovely Chhabra, Arunima Nath, Vipin Kumar Dept. of Pharmaceutics, Institute of Pharmaceutical Sciences, Kurukshetra University, Kurukshetra, Haryana