14dpo/Beta Hell

I rearranged my work schedule to go in for another beta today. I knew it wasn't a good sign when no one called me with the results.  My last great beta, which I think was Quinn's cycle, two separate nurses both called me because they wanted to be the one to tell me. Today I had to call them.

It's 64. Roughly 46 hour doubling time. Which doesn't sound bad, but at hcg levels this low, doubling should be closer to 33 hours.

I am so scared that something is wrong with the baby. Some trisomy that's leading to slow growth. Something that will let us get a few more weeks in, maybe through an ultrasound or two, before the pregnancy ends. There are few worse possibilities given my TAC, age, and my Asherman's. Anything that risks more uterine scarring, makes me even older before we can try again is really, really bad news.

I know strong betas can end that same way - heck my first blighted ovum had beautifully dark lines on hpts, but dear god I would appreciate either something reassuring, or a quick end to this. I really, really promised myself this cycle that I'd try to enjoy being pregnant for as long as I could, and then the lines started getting lighter and it just hurts. A lot. I forgot how much early losses hurt.

I go back again on Saturday to see what the numbers are doing. I try to remember that it "took" three miscarriages before we conceived the twins, so maybe we're just repeating that pattern.

14dpt/12dpo

There were sill two lines on a home test this morning, so although they were no darker and I'm still bleeding, I made the trip to my clinic and shelled out the $325 for blood work. 

Hcg 29

Progesterone 47

Estrogen ~680

Two of those three numbers are good. Sadly, they're the two I could do something about if they weren't good.

They want me back on Tuesday for re-draw, but their earliest appointment is too late for my work schedule that day. In utter nonsense, they won't let me come on Wednesday, but I could go on Thursday  . . . .only that appointment is even later. I'll figure it out on Monday. Right now I'm just sad enough to not care. 

Plan for the next month: 1) regroup with RE; 2) schedule consult with fertility acupuncture specialist; 3) starting next week, go back to strict anti-inflammatory diet; 4) research autoimmune protocols. 

We can get pregnant. It's not hopeless. But I sure as hell feel hopeless right now. 

13dpt/11dpo

Started spotting late last night. Nothing more yet this morning, but today's test shows no progression from yesterday's.

I'm going to call it as chemical #4. I'm so sorry little emrbyo(s). :(

Now the interesting question - my last treatment cycle, I had a strong BFP the afternoon of 12 days post trigger, followed by a stark BFN the evening of 14 days post trigger. CD1 was 17 days post trigger, but by 18 days post trigger, I still had enough hcg in my system to prevent me from cycling again. So, do I risk the $570 it would cost for a baseline appointment this time, or do I just take a cycle off? I think I want to schedule a regroup to see if we should change anything - viagra or acupuncture for my lining, autoimmune protocol, etc.

12dpt/10dpo

Cramping? Check and more check!
Racing resting heart rate? Check!
Intermittent, mild nausea? Check!
Burping? Check!
Mild head-cold symptoms? Check!
Intermittent breast pain? Check!

Two lines, one very faint, but darker than yesterday's? Check!

Shame on me, I looked up the due date for this cycle. November 6. Two years to the day I went into labor with the twins. I might have ugly cried before going to hug the girls' bears for a long time.

I keep repeating to myself: this time will be different. This time it will be ok. Beta on Sunday if two lines are still appearing.

Stress Kills. . . .Actually, It Doesn't

Earlier this week, my boss asked me to work on a 'Stress Management' training session. Someone on the team had created it, but it covered basics, and my boss wanted to elevate it. I started looking for interesting source material, and came upon a fascinating study.

This was done in the US. They surveyed a broad group of people. I'm paraphrasing here, but the gist is that they asked "how much stress did you have in the last year?" They also asked "How much did stress impact your health?" Then, they followed the people and watched death records for the next ~5 years.

What they found was fascinating! The people who said they had a lot of stress and that stress impacted their health were much more likely to have died over the course of the study period. The people who said they had a lot of stress, but that didn't report it impacting their health had no increased risk of death. The study's authors attributed over 20,000 US deaths a year simply to the personal belief that one's life was very stressful and that stress impacted one's health. In other words, 20,000 deaths a year because of mindset alone.

Now, I really don't believe you can kill yourself with your mind, so I take this study with a grain of salt! I certainly could see that those who think their health is impacted by high stress might feel too overwhelmed to adopt effective coping strategies. I guess the moral of the story that I take away is that it can't hurt to take steps to help mitigate how I think stress impacts me. I like the study as a reminder to keep up my coping strategies, and to hold firm in my belief that those coping strategies overcome the impact of stress.

On that note, I'm off to cope via a cookie! :)

Resemblence to a Petri Dish

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For your daily dose of nerd, here's a 1993 study in Human Reproduction that looked at embryo hcg production in vitro. They found that the embryos started to secrete hcg after a certain minimum time (160 hours post-insemination, which is 6.7 days), even when in vitro. Amazingly hcg peaked around day 10.   I like reading this, as I'm 6dpo with zero symptoms today. Which is explained by the fact that hcg production doesn't start until, at minimum, 7 days from fertilization!

I've always wondered exactly how you can test positive when a chemical pregnancy occurs, since so many popular sources say that hcg isn't produced until implantation occurs, and implantation seems to be my issue. Another 1991 study suggests an answer that question. This study found that embryos could remain viable in a petri dish up to day 14, with maximum hcg of 51 at day 10. Some of the studied embryos even adhered to the medium in the petri dish. I guess my crappy lining is about equivalent to a petri dish, given the number of day 10 bfps I've gotten that have turned into chemical pregnancies. This study also didn't find hcg production until 8 days out.

While I'm as profoundly pro-choice as it gets, I find myself sad when I think of those embryos in petri dishes, trying to grow somewhere that was never going to be hospitable. I'm not sure that's a rational feeling, as the thought of a woman making a choice to end a pregnancy doesn't make me sad in the same way. Maybe it's an empathy thing: I see the struggle my own embryos have faced in what those in the petri dishes went through. Maybe it's the fact that to me, being pro-choice means valuing a woman's autonomy, whereas the situation the embryos faced was never a decision between maternal autonomy and embryonic potential. This study was from the early 90's, before the days of embryo adoption, as far as I know. I don't fault the parents of the embryos, I just feel sad for them in their petri dishes.


Here's hoping if I've got embryo(s) still growing that they find a safer, healthier home!

Demanding as Always

By this time next week, I'll be 10 dpo and have a pretty good idea if this cycle reached what I consider to be "stage two": biochemical pregnancy. Next Sunday would be beta day, if I get a positive home test. I'm still far enough out to be calm about it. If anything fertilized, and if it started to correctly divide, it would be reaching morula stage in the next 24 hours or less: That means 16 cells, which are starting to compact as they prepare to head to the blastocyst stage. There's some research to suggest that embryos that reach morula earlier do better than those that reach it late, and "sibling" embryos of those who reach morula early do better than siblings who reach it late. Thus, I'm hoping there's life inside me and it's reaching morula now!

In IVF settings, the big fall-off is between the 6-8 cell stage and blastocyst stage, so I'm also hoping that if anything is growing, it it's healthy and able to keep dividing through to blastocyst and beyond. Our recurrent chemical pregnancies suggest that my issues tend to happen later in the game: in that 7 to 10 day range when the embryo should be hatching and implanting.

As for the rest of the stages as I've defined them, I consider appropriately doubling betas to be "stage three." I've only made it to stage three in half of my pregnancies, so it's a stressful time. Stage four is a heartbeat, or a clinical pregnancy, and on that we're two of six pregnancies. Stage five is normal chromosome results and still having a heartbeat at 12 weeks. Once again, two of six. Stage six is viability, where we're at zero. I want to make it there. I'm not even ready to consider the existence of a stage seven, just let me get to six, please, then we'll talk!

Reading this, I realize just how demanding I am! In my head, I sound like a petulant child: "I want my eggs to fertilize and grow. I want my betas to double. I want to see a heartbeat and get good NPT results. I want a living baby. I want, I want I want." On one hand, I feel guilty about making all these demands of my body, and any life inside it. On the other hand, this is basic survival of the species! Wanting this isn't abnormal or inappropriate, right? Is there a point when I need to tell the petulant child to shut up and just let things be? There probably is, but I guess I'm not there yet. I wonder how one even knows they've reached that point, much less comes to terms with it?

Implantation, Hcg Rise, and Sex!

The emotional roller coaster keeps going. Assuming the trigger worked as it should, today is 1 DPO. I went from decently optimistic the day after trigger to more pessimistic today. No real reason for that. I'm usually really fortunate in that I have very few side effects from the stim meds. In fact, my estrogen and progesterone are so low when not stimming that I typically have night sweats, and those go away during stims, so it's a nice change! This time I've noticed much more bloating, especially after trigger. I can't tell with any certainty if my ovaries are sore of if it's just my colon, but on the whole, this cycle has been more symptomatic than past. Bummer.

Because I enjoy thinking about what might be happening, fertility wise, here are a few articles on the topic of 'when does implantation happen' and 'when is hcg detectable'? I tried to focus on results from top-tier publications.


This 1999 study, published in the NEJM, used daily hormone measurements to track ovulation and identify implantation based upon the first day of detectable hcg. Then they compared implantation day with outcomes. They found that in the majority of pregnancies (84%), implantation occurred on days 8, 9, or 10. The percentage of pregnancies ending in early loss was highly correlated with implantation day: 82% of pregnancies with implantation after day 11 ended in early losses, compared to 13% of pregnancies that implanted by the ninth day. Perhaps this is why my clinic has me test at 14 days post trigger/12 days post ovulation? That seems low compared to many other places, but makes sense in light of this.

N Engl J Med. 1999 Jun 10;340(23):1796-9.

METHODS:
We collected daily urine samples for up to six months from 221 women attempting to conceive after ceasing to use contraception. Ovulation was identified on the basis of the ratio of urinary estrogen metabolites to progesterone metabolites, which changes rapidly with luteinization of the ovarian follicle. The time of implantation was defined by the appearance of chorionic gonadotropin in maternal urine.

RESULTS:
There were 199 conceptions, for 95 percent of which (189) we had sufficient data for analysis. Of these 189 pregnancies, 141 (75 percent) lasted at least six weeks past the last menstrual period, and the remaining 48 pregnancies (25 percent) ended in early loss. Among the pregnancies that lasted six weeks or more, the first appearance of chorionic gonadotropin occurred 6 to 12 days after ovulation; 118 women (84 percent) had implantation on day 8, 9, or 10. The risk of early pregnancy loss increased with later implantation (P<0.001). Among the 102 conceptuses that implanted by the ninth day, 13 percent ended in early loss. This proportion rose to 26 percent with implantation on day 10, to 52 percent on day 11, and to 82 percent after day 11.


Another situation I've always wondered: I read that hcg is supposed to double roughly every 48 hours during the early weeks. But given that it must start from 0, how do you get from 0 to detectable in only a few days? This study looked at hcg patterns, and found a 3-fold rise between the day hcg is first detected and the next day. The rate of increase later dropped to 1.6x by days 6 and 7 after detection (roughly 4 weeks pregnant, and the time of the first beta).

Hum Reprod. 2008 Feb;23(2):271-7. Epub 2007 Dec 14.
METHODS:
We measured daily hCG concentrations in first-morning urine for 142 clinical pregnancies from women with no known fertility problems. Mixed-effects regression models were used to estimate the hCG trajectory and its variability in relation to pregnancy outcomes.

RESULTS:
hCG rose 3-fold between the day of detection and the next day (95% CI = 2.7-3.4). The relative rate of rise decreased thereafter, reaching 1.6-fold (95% CI = 1.5-1.8) between days 6 and 7. HCG levels followed a log-quadratic trajectory, and the patterns of rise were unrelated to number of fetuses, risk of spontaneous abortion or sex of the baby. Later implantations (after 10 luteal days) produced slower rates of increase.

CONCLUSIONS:
Although mean hCG follows a log-quadratic trajectory during the first week of detectability, there is high variability across pregnancies. Later implantation may reflect characteristics of the uterus or conceptus that slow hCG production.


Finally, to the question of when to have timed intercourse, here's another NJEM-published study looking at fertile people. There are a number of these studies, but I like this one because it used hormones to track ovulation, rather than relying on temperature records, which are more unreliable. The study found the highest probability of conception when TI occurred the day before ovulation. Another paper, reviewing many on the subject, noted that studies where ovulation is determined by hormones typically find the day before ovulation to have the highest probability of conception, while studies where ovulation is determined by basal temperature/charting typically find the day of ovulation to have the highest probability. I trust hormones more than temperatures, so I'll assume day before is optimal based on what we know.

N Engl J Med. 1995 Dec 7;333(23):1517-21.
METHODS:
We recruited 221 healthy women who were planning to become pregnant. At the same time the women stopped using birth-control methods, they began collecting daily urine specimens and keeping daily records of whether they had sexual intercourse. We measured estrogen and progesterone metabolites in urine to estimate the day of ovulation.

RESULTS:
In a total of 625 menstrual cycles for which the dates of ovulation could be estimated, 192 pregnancies were initiated, as indicated by increases in the urinary concentration of human chorionic gonadotropin around the expected time of implantation. Two thirds (n = 129) ended in live births. Conception occurred only when intercourse took place during a six-day period that ended on the estimated day of ovulation. The probability of conception ranged from 0.10 when intercourse occurred five days before ovulation to 0.33 when it occurred on the day of ovulation itself. There was no evident relation between the age of sperm and the viability of the conceptus, although only 6 percent of the pregnancies could be firmly attributed to sperm that were three or more days old. Cycles producing male and female babies had similar patterns of intercourse in relation to ovulation.

Microblog Monday: I've Always Been Mature for My Age

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Being the nerdly type I've always been, I spent a decent portion of lunch time today reviewing the published literature about success rates based on endometrial lining thickness and oocyte maturity based on follicle size. I know I have no control over what happens for the next two weeks, but obsessively reading related information is my coping strategy! 

To my extreme irritation, I deleted my entire list of endometrial thickness references, but for anyone who wonders 'what size follicle can produce a mature egg', here are a few gems.

Follicles as small as 12-14.5mm, on the day of retrieval, have up to 80% of eggs mature (e.g., metaphase II). However, fertilization was only 47% in this group, compared to 67% in eggs from follicles 18.5mm and grater.
Source: Mehri, Levi Setti, Greco, Sakkas, Martinez, Patrizio, J Assist Reprod Genet., 2014.  https://www.ncbi.nlm.nih.gov/pubmed/24189964

Follicles greater than 14 on the day of retrieval produce recoverable eggs 85.5% of the time, follicles from 10-14 do 79.6% of the time. Of those retrieved greater than 14 on day of retrieval, 93.3% are mature, while those 10-14 show 81% mature. The larger eggs fertilize 80% of the time, while the smaller do 75.4% of the time. The biggest difference? The larger follicles produce a higher percentage of embryos scored as "good" by the study researchers. Source: Triwitayakorn, Suwajanakorn,1 Pruksananonda, Sereepapong, and Ahnonkitpanit. J Assist Reprod Genet., 2003. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3455636/pdf/10815_2004_Article_461190.pdf To be fair, those numbers seem implausibly high to me, but interesting none the less.

Try as I might, I couldn't find any evidence regarding what size follicles will ovulate during a OI/TI cycle, when no retrieval occurs. I'll assume I had two mature, and go from there.

Trigger Time

Just got the call from my monitoring appointment today. Since my lining has shrunk, and my E2's not rising much, it's time for trigger tonight. I'm just going to hope that 5.5 and triple stripe is good enough. It seems impossible to believe that my lining was really at 7.7, and I've noticed the sonographer who did most of my scans this time is the one who seems to have the most variability from one appointment to the next. Thus, I'll take all this with a grain (shaker) of salt, and hope for the best. Overall, I'm really pleased with the fact that my lining did get to trilaminar, even if too thin, and that my ovaries seem capable of at least some growth. Test at home in two weeks.

To warm my data loving heart, here's the final tracking of this cycle.

Stim Day		7/16	2/17	12/17	2/18
	AFC	9	4	7	5
4	L follies	11, 9, 8.5	6.5	3.5, 4	14, 11, 8.5
	R follies	12.5, 8, 8	9.8	12, 10.5	7,4
	E2	803		188	622
	P4	2.68	<.05	<.05	0.07
	LH	8.24 miu		3.38	2.12
	Lining	6.9 triple	5.9 triple	4 uniform	5.5 triple
	FSH	600	600	900	1100
	Menopur		0	300	300
	Day	7	7	7	6
6 - 7	L follies	16.5, 15, 10, 8	9.5	6, 8	16, 13.5, 9.5
	R follies	19, 13.6, 7	14.5	20, 17.5	9
	E2	1294	432	718	1023
	P4	1.66	<.05	0.07	0.08
	LH	1.03	1.15	2.8	1.61
		6.9 triple	7.0 triple	6 homogenous	7.77 mixed
	FSH	1050	1275	1575	1350
	Menopur		0	525	450
	Day	8	9	9	8
8-9	L follies	18, 16, 10, 8	11	7.5	21.5, 17, 13.5, 6
	R follies	22, 18, 7, 4	16.5	20.5, 18	14.5, 9, 6.5
	E2	1690	1027	1087	1132
	P4	2.59	0.12	0.18	0.1
	LH	0.76	1.15	3.18	0.72
		6.9 triple	6.0 triple	5 mixed	5.5 triple
	FSH	1200	1875	2025	2200
	Menopur	0	0	675	675
	Day		11	10
10-11	L follies		14	7.5
	R follies		20.8	24, 20.5
	E2
	P4
	LH
	FSH		2475	2250
	Menopur			750

Monitoring #2, February

It seemed very odd that the clinic wanted me back today, after only 6 full days of stims. That seemed to early, since it's usually after 7 full days and I'm NEVER ready by then. Still, with my lining issues, I trusted them. Earlier would mean more time to course correct, right? Yeah, day 6, way too early. To paraphrase: Keep on same dosage for another two days, return on Sunday. That'll be $570, thank you.

My lining isn't the right pattern, but at least it's growing. I am guardedly hopeful.

  

Stim Day		7/16	2/17	12/17	2/18
	AFC	9	4	7	5
4	L follies	11, 9, 8.5	6.5	3.5, 4	14, 11, 8.5
	R follies	12.5, 8, 8	9.8	12, 10.5	7,4
	E2	803		188	622
	P4	2.68	<.05	<.05	0.07
	LH	8.24 miu		3.38	2.12
	Lining	6.9 triple	5.9 triple	4 uniform	5.7 triple
	FSH	600	600	900	1100
	Menopur	0	0	300	300
	Day	7	7	7	6
6 - 7	L follies	16.5, 15, 10, 8	9.5	6, 8	16, 13.5, 9.5
	R follies	19, 13.6, 7	14.5	20, 17.5	9
	E2	1294	432	718	1023
	P4	1.66	<.05	0.07	0.08
	LH	1.03	1.15	2.8	1.61
		6.9 triple	7.0 triple	6 homogenous	7.77 mixed
	FSH	1050	1275	1575	1350
	Menopur	0	0	525	450